Jen Smith

Micrograph showing CLL

LUGANO, SWITZERLAND—A sequential treatment regimen can produce a high overall response rate (ORR) in patients with treatment-naïve (TN) or relapsed/refractory (RR) chronic lymphocytic leukemia (CLL), results of the CLL2-BAG study suggest.

Patients who received bendamustine followed by obinutuzumab and venetoclax achieved an ORR of 95%, and 87% of them were negative for minimal residual disease (MRD) in the peripheral blood.

In addition, this regimen did not lead to cumulative or unexpected toxicity, according to study investigator Paula Cramer, MD, of University Hospital of Cologne in Germany.

Dr Cramer presented results from CLL2-BAG at the 14th International Conference on Malignant Lymphoma (ICML). The trial was sponsored by the German CLL Study Group.

CLL2-BAG included 63 patients—34 with TN and 29 with RR CLL. The median age was 58 (range, 43-76) and 61 (range, 28-77), respectively.

Thirty-five percent of TN patients had bulky disease (>5 cm), as did 45% of RR patients. Twelve percent and 10%, respectively, had massive splenomegaly (>20 cm)

Twenty-one percent of TN patients and 35% of RR patients were Binet stage A. Thirty-two percent and 21%, respectively, were stage B, and 47% and 45%, respectively, were stage C.

Treatment

Patients first underwent debulking with bendamustine, given at 70 mg/m² on days 1 and 2 for two 28-day cycles. They then received induction with obinutuzumab and venetoclax for six 28-day cycles.

In cycle 1, patients received obinutuzumab at 100 mg or 900 mg on day 1 or 2 and 1000 mg on days 8 and 15. For cycles 2-6, patients received 1000 mg of obinutuzumab on day 1.

In cycle 2, patients received venetoclax at 20 mg on days 1-7, 50 mg on days 8-14, 100 mg on days 15-21, and 200 mg on days 22-28. For cycles 3-6, they received venetoclax at 400 mg on days 1-28.

Patients also received maintenance with obinutuzumab and venetoclax for 2 to 8 cycles with a duration of 84 days. Obinutuzumab was given at 1000 mg on day 1 of each cycle, and venetoclax was given at 400 mg on days 1-84.

Maintenance was continued until patients completed 24 months of maintenance therapy, until 3 months after patients achieved a complete response (CR) or CR with incomplete count recovery (CRi) and MRD negativity, until progression of CLL or start of new CLL treatment, or until unacceptable toxicity.

ORR, MRD, and survival

At the end of induction, the ORR was 95% in the entire population—100% among TN patients and 90% among RR patients.

The rate of CR was 8%, 9%, and 7%, respectively. The rate of unconfirmed/clinical CR/CRi was 32%, 41%, and 21%, respectively.

Five percent of patients progressed, all of them in the RR group.

Eighty-seven percent of evaluable patients were MRD negative (<10^-4) in the peripheral blood, including 91% of TN patients and 83% of RR patients. Two patients (3%) were missing data on MRD status in peripheral blood.

Thirteen percent of all evaluable patients were MRD negative in the bone marrow, including 12% of TN patients and 14% of RR patients. The remaining patients (87%, 88%, and 86%, respectively) were missing data on MRD status in the bone marrow.

The progression-free survival at 15 months was 100% in the TN patients and 83% in the RR patients.

Adverse events

After debulking, 28.1% of TN patients and 46.7% of RR patients had experienced adverse events (AEs).

These included (in TN and RR patients, respectively) neutropenia (9.4% and 13.3%), anemia (6.3% and 20.0%), thrombocytopenia (6.3% and 6.7%), infections (6.3% and 6.7%), coronary artery disorders (1 TN patient, 3.1%), rash (1 TN patient, 3.1%), tumor lysis syndrome (1 TN patient, 3.1%), vomiting (1 TN patient, 3.1%), and pyrexia (1 RR patient, 6.7%).

After induction, 54.3% of TN patients and 80.6% of RR patients had experienced AEs.

These included (in TN and RR patients, respectively) neutropenia (34.3% and 54.8%), infections (8.6% and 29.0%), thrombocytopenia (2.9% and 22.6%), infusion-related reactions (5 RR patients, 16.1%), neoplasms (2.9% and 9.7%), hypertension (2.9% and 6.5%), coronary artery disorders (2.9% and 6.5%), anemia (3 RR patients, 9.7%), and tumor lysis syndrome (2 RR patients, 6.5%).

Micrograph showing CLL

LUGANO, SWITZERLAND—A sequential treatment regimen can produce a high overall response rate (ORR) in patients with treatment-naïve (TN) or relapsed/refractory (RR) chronic lymphocytic leukemia (CLL), results of the CLL2-BAG study suggest.

Patients who received bendamustine followed by obinutuzumab and venetoclax achieved an ORR of 95%, and 87% of them were negative for minimal residual disease (MRD) in the peripheral blood.

In addition, this regimen did not lead to cumulative or unexpected toxicity, according to study investigator Paula Cramer, MD, of University Hospital of Cologne in Germany.

Dr Cramer presented results from CLL2-BAG at the 14th International Conference on Malignant Lymphoma (ICML). The trial was sponsored by the German CLL Study Group.

CLL2-BAG included 63 patients—34 with TN and 29 with RR CLL. The median age was 58 (range, 43-76) and 61 (range, 28-77), respectively.

Thirty-five percent of TN patients had bulky disease (>5 cm), as did 45% of RR patients. Twelve percent and 10%, respectively, had massive splenomegaly (>20 cm)

Twenty-one percent of TN patients and 35% of RR patients were Binet stage A. Thirty-two percent and 21%, respectively, were stage B, and 47% and 45%, respectively, were stage C.

Treatment

Patients first underwent debulking with bendamustine, given at 70 mg/m² on days 1 and 2 for two 28-day cycles. They then received induction with obinutuzumab and venetoclax for six 28-day cycles.

In cycle 1, patients received obinutuzumab at 100 mg or 900 mg on day 1 or 2 and 1000 mg on days 8 and 15. For cycles 2-6, patients received 1000 mg of obinutuzumab on day 1.

In cycle 2, patients received venetoclax at 20 mg on days 1-7, 50 mg on days 8-14, 100 mg on days 15-21, and 200 mg on days 22-28. For cycles 3-6, they received venetoclax at 400 mg on days 1-28.

Patients also received maintenance with obinutuzumab and venetoclax for 2 to 8 cycles with a duration of 84 days. Obinutuzumab was given at 1000 mg on day 1 of each cycle, and venetoclax was given at 400 mg on days 1-84.

Maintenance was continued until patients completed 24 months of maintenance therapy, until 3 months after patients achieved a complete response (CR) or CR with incomplete count recovery (CRi) and MRD negativity, until progression of CLL or start of new CLL treatment, or until unacceptable toxicity.

ORR, MRD, and survival

At the end of induction, the ORR was 95% in the entire population—100% among TN patients and 90% among RR patients.

The rate of CR was 8%, 9%, and 7%, respectively. The rate of unconfirmed/clinical CR/CRi was 32%, 41%, and 21%, respectively.

Five percent of patients progressed, all of them in the RR group.

Eighty-seven percent of evaluable patients were MRD negative (<10^-4) in the peripheral blood, including 91% of TN patients and 83% of RR patients. Two patients (3%) were missing data on MRD status in peripheral blood.

Thirteen percent of all evaluable patients were MRD negative in the bone marrow, including 12% of TN patients and 14% of RR patients. The remaining patients (87%, 88%, and 86%, respectively) were missing data on MRD status in the bone marrow.

The progression-free survival at 15 months was 100% in the TN patients and 83% in the RR patients.

Adverse events

After debulking, 28.1% of TN patients and 46.7% of RR patients had experienced adverse events (AEs).

These included (in TN and RR patients, respectively) neutropenia (9.4% and 13.3%), anemia (6.3% and 20.0%), thrombocytopenia (6.3% and 6.7%), infections (6.3% and 6.7%), coronary artery disorders (1 TN patient, 3.1%), rash (1 TN patient, 3.1%), tumor lysis syndrome (1 TN patient, 3.1%), vomiting (1 TN patient, 3.1%), and pyrexia (1 RR patient, 6.7%).

After induction, 54.3% of TN patients and 80.6% of RR patients had experienced AEs.

These included (in TN and RR patients, respectively) neutropenia (34.3% and 54.8%), infections (8.6% and 29.0%), thrombocytopenia (2.9% and 22.6%), infusion-related reactions (5 RR patients, 16.1%), neoplasms (2.9% and 9.7%), hypertension (2.9% and 6.5%), coronary artery disorders (2.9% and 6.5%), anemia (3 RR patients, 9.7%), and tumor lysis syndrome (2 RR patients, 6.5%).

Micrograph showing CLL

LUGANO, SWITZERLAND—A sequential treatment regimen can produce a high overall response rate (ORR) in patients with treatment-naïve (TN) or relapsed/refractory (RR) chronic lymphocytic leukemia (CLL), results of the CLL2-BAG study suggest.

Patients who received bendamustine followed by obinutuzumab and venetoclax achieved an ORR of 95%, and 87% of them were negative for minimal residual disease (MRD) in the peripheral blood.

In addition, this regimen did not lead to cumulative or unexpected toxicity, according to study investigator Paula Cramer, MD, of University Hospital of Cologne in Germany.

Dr Cramer presented results from CLL2-BAG at the 14th International Conference on Malignant Lymphoma (ICML). The trial was sponsored by the German CLL Study Group.

CLL2-BAG included 63 patients—34 with TN and 29 with RR CLL. The median age was 58 (range, 43-76) and 61 (range, 28-77), respectively.

Thirty-five percent of TN patients had bulky disease (>5 cm), as did 45% of RR patients. Twelve percent and 10%, respectively, had massive splenomegaly (>20 cm)

Twenty-one percent of TN patients and 35% of RR patients were Binet stage A. Thirty-two percent and 21%, respectively, were stage B, and 47% and 45%, respectively, were stage C.

Treatment

Patients first underwent debulking with bendamustine, given at 70 mg/m² on days 1 and 2 for two 28-day cycles. They then received induction with obinutuzumab and venetoclax for six 28-day cycles.

In cycle 1, patients received obinutuzumab at 100 mg or 900 mg on day 1 or 2 and 1000 mg on days 8 and 15. For cycles 2-6, patients received 1000 mg of obinutuzumab on day 1.

In cycle 2, patients received venetoclax at 20 mg on days 1-7, 50 mg on days 8-14, 100 mg on days 15-21, and 200 mg on days 22-28. For cycles 3-6, they received venetoclax at 400 mg on days 1-28.

Patients also received maintenance with obinutuzumab and venetoclax for 2 to 8 cycles with a duration of 84 days. Obinutuzumab was given at 1000 mg on day 1 of each cycle, and venetoclax was given at 400 mg on days 1-84.

Maintenance was continued until patients completed 24 months of maintenance therapy, until 3 months after patients achieved a complete response (CR) or CR with incomplete count recovery (CRi) and MRD negativity, until progression of CLL or start of new CLL treatment, or until unacceptable toxicity.

ORR, MRD, and survival

At the end of induction, the ORR was 95% in the entire population—100% among TN patients and 90% among RR patients.

The rate of CR was 8%, 9%, and 7%, respectively. The rate of unconfirmed/clinical CR/CRi was 32%, 41%, and 21%, respectively.

Five percent of patients progressed, all of them in the RR group.

Eighty-seven percent of evaluable patients were MRD negative (<10^-4) in the peripheral blood, including 91% of TN patients and 83% of RR patients. Two patients (3%) were missing data on MRD status in peripheral blood.

Thirteen percent of all evaluable patients were MRD negative in the bone marrow, including 12% of TN patients and 14% of RR patients. The remaining patients (87%, 88%, and 86%, respectively) were missing data on MRD status in the bone marrow.

The progression-free survival at 15 months was 100% in the TN patients and 83% in the RR patients.

Adverse events

After debulking, 28.1% of TN patients and 46.7% of RR patients had experienced adverse events (AEs).

These included (in TN and RR patients, respectively) neutropenia (9.4% and 13.3%), anemia (6.3% and 20.0%), thrombocytopenia (6.3% and 6.7%), infections (6.3% and 6.7%), coronary artery disorders (1 TN patient, 3.1%), rash (1 TN patient, 3.1%), tumor lysis syndrome (1 TN patient, 3.1%), vomiting (1 TN patient, 3.1%), and pyrexia (1 RR patient, 6.7%).

After induction, 54.3% of TN patients and 80.6% of RR patients had experienced AEs.

These included (in TN and RR patients, respectively) neutropenia (34.3% and 54.8%), infections (8.6% and 29.0%), thrombocytopenia (2.9% and 22.6%), infusion-related reactions (5 RR patients, 16.1%), neoplasms (2.9% and 9.7%), hypertension (2.9% and 6.5%), coronary artery disorders (2.9% and 6.5%), anemia (3 RR patients, 9.7%), and tumor lysis syndrome (2 RR patients, 6.5%).

Andrew Wei, MBBS, PhD

MADRID—The combination of venetoclax and low-dose cytarabine (VEN+LDAC) appears to be a feasible treatment option for elderly patients with untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.

In a phase 1/2 study of such patients, VEN+LDAC was considered well-tolerated, conferring moderate myelosuppression and largely low-grade non-hematologic toxicities.

In addition, the combination produced “rapid and durable” responses, and early death rates were low, according to Andrew H. Wei, MBBS, PhD, of Monash University in Melbourne, Victoria, Australia.

However, nearly three-quarters of patients ultimately discontinued the treatment, many due to disease progression.

Dr Wei presented these results at the 22nd Congress of the European Hematology Association (EHA) as abstract S473. AbbVie and Genentech, the companies developing and marketing venetoclax, provided financial support for this study.

“Expression of pro-survival proteins is an established mechanism of chemoresistance in diverse cancers,” Dr Wei noted. “BCL-2 is 1 of 5 pro-survival molecules which functions to sequester pro-apoptotic molecules and tip the balance in favor of cell survival.”

“Venetoclax is a potent and specific inhibitor of BCL-2 which releases these pro-apoptotic molecules, tipping the balance in favor of cell death. Cytotoxic drugs are well-known to increase the burden of BH3-only proteins, and so it was surmised that the combination of chemotherapy, such as cytarabine, with venetoclax could augment the clinical response.”

Patients

Dr Wei presented data on 61 AML patients treated with VEN+LDAC. He noted that this was a poor-risk population, with nearly half of patients over the age of 75 at baseline.

The patients’ median age was 74 (range, 66-87), and 64% were male. Nearly half of patients had an ECOG performance status of 1 (49%), 30% had a status of 0, and 21% had a status of 2.

Forty-four percent of patients had secondary AML, and 28% had prior treatment with a hypomethylating agent (HMA). Sixty-one percent of patients had intermediate-risk cytogenetics, and 31% had poor-risk cytogenetics.

Treatment

The patients received oral venetoclax at 600 mg daily on days 1 to 28 and subcutaneous cytarabine at 20 mg/m² daily on days 1 to 10 of each 28-day cycle.

In the first cycle, the dose of venetoclax was ramped up gradually—no dose on day 1, 50 mg on day 2, 100 mg on day 3, 200 mg on day 4, 400 mg on day 5, and 600 mg thereafter.

Patients received prophylaxis for tumor lysis syndrome prior to starting cycle 1, and they were hospitalized to enable observation.

The median time on study treatment was 6 months (range, <1 to 19 months). Seventy-two percent of patients discontinued treatment.

Reasons for discontinuation included:

• Progressive disease without death—26%
• Progressive disease with death—10%
• Adverse event (AE) related to progression—10%
• AE not related to progression—8%
• Withdrawn consent—8%
• Other reasons—18%.

Safety

The most common AEs of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).

Grade 3/4 hematologic AEs (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), and anemia (28%).

Grade 3/4 non-hematologic AEs (occurring in at least 10% of patients) included hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).

Response and survival

The overall response rate was 65%, with 25% of patients achieving a complete response (CR), 38% having a CR with incomplete blood count recovery (CRi), and 2% experiencing a partial response.

Dr Wei noted that VEN+LDAC was active across subgroups.

The CR/CRi rate was 76% among patients with intermediate-risk cytogenetics and 47% among patients with poor-risk cytogenetics.

The CR/CRi rate was 70% among patients older than 75, 52% among patients with secondary AML, 66% among patients with no prior HMA exposure, and 53% in patients with prior HMA exposure.

“Although responses were slightly lower in patients with poor cytogenetic risk, prior HMA exposure, and secondary AML . . ., these responses are far in excess of what we would expect with [LDAC] alone,” Dr Wei said.

“Furthermore, the median time to response was very rapid, and this is extremely important to get patients into remission and avoid the medium-term consequences of active AML.”

The median time to response was 1 month (range, <1 to 9 months).

The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.

Based on these results, AbbVie has initiated a phase 3 trial comparing VEN+LDAC to LDAC alone in elderly patients with untreated AML who are ineligible for intensive chemotherapy.

Andrew Wei, MBBS, PhD

MADRID—The combination of venetoclax and low-dose cytarabine (VEN+LDAC) appears to be a feasible treatment option for elderly patients with untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.

In a phase 1/2 study of such patients, VEN+LDAC was considered well-tolerated, conferring moderate myelosuppression and largely low-grade non-hematologic toxicities.

In addition, the combination produced “rapid and durable” responses, and early death rates were low, according to Andrew H. Wei, MBBS, PhD, of Monash University in Melbourne, Victoria, Australia.

However, nearly three-quarters of patients ultimately discontinued the treatment, many due to disease progression.

Dr Wei presented these results at the 22nd Congress of the European Hematology Association (EHA) as abstract S473. AbbVie and Genentech, the companies developing and marketing venetoclax, provided financial support for this study.

“Expression of pro-survival proteins is an established mechanism of chemoresistance in diverse cancers,” Dr Wei noted. “BCL-2 is 1 of 5 pro-survival molecules which functions to sequester pro-apoptotic molecules and tip the balance in favor of cell survival.”

“Venetoclax is a potent and specific inhibitor of BCL-2 which releases these pro-apoptotic molecules, tipping the balance in favor of cell death. Cytotoxic drugs are well-known to increase the burden of BH3-only proteins, and so it was surmised that the combination of chemotherapy, such as cytarabine, with venetoclax could augment the clinical response.”

Patients

Dr Wei presented data on 61 AML patients treated with VEN+LDAC. He noted that this was a poor-risk population, with nearly half of patients over the age of 75 at baseline.

The patients’ median age was 74 (range, 66-87), and 64% were male. Nearly half of patients had an ECOG performance status of 1 (49%), 30% had a status of 0, and 21% had a status of 2.

Forty-four percent of patients had secondary AML, and 28% had prior treatment with a hypomethylating agent (HMA). Sixty-one percent of patients had intermediate-risk cytogenetics, and 31% had poor-risk cytogenetics.

Treatment

The patients received oral venetoclax at 600 mg daily on days 1 to 28 and subcutaneous cytarabine at 20 mg/m² daily on days 1 to 10 of each 28-day cycle.

In the first cycle, the dose of venetoclax was ramped up gradually—no dose on day 1, 50 mg on day 2, 100 mg on day 3, 200 mg on day 4, 400 mg on day 5, and 600 mg thereafter.

Patients received prophylaxis for tumor lysis syndrome prior to starting cycle 1, and they were hospitalized to enable observation.

The median time on study treatment was 6 months (range, <1 to 19 months). Seventy-two percent of patients discontinued treatment.

Reasons for discontinuation included:

• Progressive disease without death—26%
• Progressive disease with death—10%
• Adverse event (AE) related to progression—10%
• AE not related to progression—8%
• Withdrawn consent—8%
• Other reasons—18%.

Safety

The most common AEs of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).

Grade 3/4 hematologic AEs (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), and anemia (28%).

Grade 3/4 non-hematologic AEs (occurring in at least 10% of patients) included hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).

Response and survival

The overall response rate was 65%, with 25% of patients achieving a complete response (CR), 38% having a CR with incomplete blood count recovery (CRi), and 2% experiencing a partial response.

Dr Wei noted that VEN+LDAC was active across subgroups.

The CR/CRi rate was 76% among patients with intermediate-risk cytogenetics and 47% among patients with poor-risk cytogenetics.

The CR/CRi rate was 70% among patients older than 75, 52% among patients with secondary AML, 66% among patients with no prior HMA exposure, and 53% in patients with prior HMA exposure.

“Although responses were slightly lower in patients with poor cytogenetic risk, prior HMA exposure, and secondary AML . . ., these responses are far in excess of what we would expect with [LDAC] alone,” Dr Wei said.

“Furthermore, the median time to response was very rapid, and this is extremely important to get patients into remission and avoid the medium-term consequences of active AML.”

The median time to response was 1 month (range, <1 to 9 months).

The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.

Based on these results, AbbVie has initiated a phase 3 trial comparing VEN+LDAC to LDAC alone in elderly patients with untreated AML who are ineligible for intensive chemotherapy.

Andrew Wei, MBBS, PhD

MADRID—The combination of venetoclax and low-dose cytarabine (VEN+LDAC) appears to be a feasible treatment option for elderly patients with untreated acute myeloid leukemia (AML) who are ineligible for intensive chemotherapy.

In a phase 1/2 study of such patients, VEN+LDAC was considered well-tolerated, conferring moderate myelosuppression and largely low-grade non-hematologic toxicities.

In addition, the combination produced “rapid and durable” responses, and early death rates were low, according to Andrew H. Wei, MBBS, PhD, of Monash University in Melbourne, Victoria, Australia.

However, nearly three-quarters of patients ultimately discontinued the treatment, many due to disease progression.

Dr Wei presented these results at the 22nd Congress of the European Hematology Association (EHA) as abstract S473. AbbVie and Genentech, the companies developing and marketing venetoclax, provided financial support for this study.

“Expression of pro-survival proteins is an established mechanism of chemoresistance in diverse cancers,” Dr Wei noted. “BCL-2 is 1 of 5 pro-survival molecules which functions to sequester pro-apoptotic molecules and tip the balance in favor of cell survival.”

“Venetoclax is a potent and specific inhibitor of BCL-2 which releases these pro-apoptotic molecules, tipping the balance in favor of cell death. Cytotoxic drugs are well-known to increase the burden of BH3-only proteins, and so it was surmised that the combination of chemotherapy, such as cytarabine, with venetoclax could augment the clinical response.”

Patients

Dr Wei presented data on 61 AML patients treated with VEN+LDAC. He noted that this was a poor-risk population, with nearly half of patients over the age of 75 at baseline.

The patients’ median age was 74 (range, 66-87), and 64% were male. Nearly half of patients had an ECOG performance status of 1 (49%), 30% had a status of 0, and 21% had a status of 2.

Forty-four percent of patients had secondary AML, and 28% had prior treatment with a hypomethylating agent (HMA). Sixty-one percent of patients had intermediate-risk cytogenetics, and 31% had poor-risk cytogenetics.

Treatment

The patients received oral venetoclax at 600 mg daily on days 1 to 28 and subcutaneous cytarabine at 20 mg/m² daily on days 1 to 10 of each 28-day cycle.

In the first cycle, the dose of venetoclax was ramped up gradually—no dose on day 1, 50 mg on day 2, 100 mg on day 3, 200 mg on day 4, 400 mg on day 5, and 600 mg thereafter.

Patients received prophylaxis for tumor lysis syndrome prior to starting cycle 1, and they were hospitalized to enable observation.

The median time on study treatment was 6 months (range, <1 to 19 months). Seventy-two percent of patients discontinued treatment.

Reasons for discontinuation included:

• Progressive disease without death—26%
• Progressive disease with death—10%
• Adverse event (AE) related to progression—10%
• AE not related to progression—8%
• Withdrawn consent—8%
• Other reasons—18%.

Safety

The most common AEs of any grade (occurring in at least 30% of patients) were nausea (74%), hypokalemia (46%), diarrhea (46%), fatigue (44%), decreased appetite (41%), constipation (34%), hypomagnesemia (34%), vomiting (31%), thrombocytopenia (44%), febrile neutropenia (38%), and neutropenia (33%).

Grade 3/4 hematologic AEs (occurring in at least 10% of patients) included thrombocytopenia (44%), febrile neutropenia (36%), neutropenia (33%), and anemia (28%).

Grade 3/4 non-hematologic AEs (occurring in at least 10% of patients) included hypokalemia (16%), hypophosphatemia (13%), and hypertension (12%).

Response and survival

The overall response rate was 65%, with 25% of patients achieving a complete response (CR), 38% having a CR with incomplete blood count recovery (CRi), and 2% experiencing a partial response.

Dr Wei noted that VEN+LDAC was active across subgroups.

The CR/CRi rate was 76% among patients with intermediate-risk cytogenetics and 47% among patients with poor-risk cytogenetics.

The CR/CRi rate was 70% among patients older than 75, 52% among patients with secondary AML, 66% among patients with no prior HMA exposure, and 53% in patients with prior HMA exposure.

“Although responses were slightly lower in patients with poor cytogenetic risk, prior HMA exposure, and secondary AML . . ., these responses are far in excess of what we would expect with [LDAC] alone,” Dr Wei said.

“Furthermore, the median time to response was very rapid, and this is extremely important to get patients into remission and avoid the medium-term consequences of active AML.”

The median time to response was 1 month (range, <1 to 9 months).

The 30-day death rate was 3%, the 60-day death rate was 15%, and the median overall survival was approximately 12 months.

Based on these results, AbbVie has initiated a phase 3 trial comparing VEN+LDAC to LDAC alone in elderly patients with untreated AML who are ineligible for intensive chemotherapy.

on Malignant Lymphoma

LUGANO, SWITZERLAND—A 4-drug regimen has demonstrated efficacy in a phase 2 trial of patients with treatment-naïve extranodal natural killer/T-cell lymphoma (ENKTL).

Treatment with gemcitabine, PEG-asparaginase, dexamethasone, and methotrexate (GAD-M) produced a 94% overall response rate (ORR) and an 83% complete response (CR) rate in this trial.

Responses and survival rates were higher in patients with stage I/II disease, who also received radiotherapy, than in patients with stage III/IV disease.

Grade 1/2 toxicities were frequent, but there were few grade 3/4 non-hematologic toxicities. One patient died of treatment-related toxicity.

Zhiming Li, of Sun Yet-sen University Cancer Center in Guangzhou, China, presented these results at the 14th International Conference on Malignant Lymphoma (ICML).

Patients and treatment

The trial enrolled 41 patients with treatment-naïve ENKTL, and 36 of them were evaluable.

The patients’ median age was 45 (range, 18-75), and 30.6% were female. Most patients (86.1%) had stage I/II disease, 13.9% had an ECOG performance status of 2 or greater, and 41.7% had an IPI score of 2 or greater.

The GAD-M regimen consisted of:

• Gemcitabine given at 1000 mg/m² via intravenous drip on days 1 and 8
• PEG-asparaginase given at 2500 U/m² intramuscularly on day 1
• Dexamethasone given at 20 mg via intravenous drip on days 1 to 3
• Methotrexate given at 3000 mg/m² via continuous, 12-hour infusion on day 1.

The regimen was repeated every 3 weeks.

For patients with stage I/II disease, 2 to 4 cycles of the GAD-M regimen was followed by extensive involved-field radiotherapy and an additional 2 to 4 cycles. For patients with stage III/IV disease, GAD-M was repeated for 6 cycles.

Response and survival

The ORR was 94.4%, both after 2 cycles of GAD-M and after 6 cycles. The CR rate was 50% after 2 cycles and 83.3% after 6 cycles.

In patients with stage I/II disease, the ORR was 100% after 2 cycles and 6 cycles. The CR rate was 54.8% after 2 cycles and 90.3% after 6 cycles.

In patients with stage III/IV disease, the ORR was 60% after 2 cycles and 6 cycles. The CR rate was 20% after 2 cycles and 40% after 6 cycles.

At median follow-up of 23.3 months, the estimated 3-year progression-free survival (PFS) was 72.1%, and the overall survival (OS) was 76.3%.

For patients with stage I/II disease, the PFS was 77.3%, and the OS was 79.3%. For patients with stage III/IV disease, the PFS was 40%, and the OS was 60%.

Safety

Hematologic adverse events (AEs) included anemia (97.2% total, 52.8% grade 3/4), leukocytopenia (94.4%, 27.8% grade 3/4), neutropenia (88.9%, 5.6% grade 3), and thrombocytopenia (47.2%, 13.9% grade 3/4).

Non-hematologic AEs included hypoalbuminemia (100%, 5.6% grade 3), increased transaminases (88.9%, 5.6% grade 3), hyperbilirubinemia (52.8%, 11.1% grade 3), decreased fibrinogen (19.4%, 11.1% grade 4), vomiting (13.9%, 2.8% grade 5), increased creatinine (8.3%, 2.8% grade 3), and abdominal pain (5.6% grade 1).

The grade 5 treatment-related AE occurred in a 61-year-old man. He died of electrolyte disorders caused by severe vomiting.

on Malignant Lymphoma

LUGANO, SWITZERLAND—A 4-drug regimen has demonstrated efficacy in a phase 2 trial of patients with treatment-naïve extranodal natural killer/T-cell lymphoma (ENKTL).

Treatment with gemcitabine, PEG-asparaginase, dexamethasone, and methotrexate (GAD-M) produced a 94% overall response rate (ORR) and an 83% complete response (CR) rate in this trial.

Responses and survival rates were higher in patients with stage I/II disease, who also received radiotherapy, than in patients with stage III/IV disease.

Grade 1/2 toxicities were frequent, but there were few grade 3/4 non-hematologic toxicities. One patient died of treatment-related toxicity.

Zhiming Li, of Sun Yet-sen University Cancer Center in Guangzhou, China, presented these results at the 14th International Conference on Malignant Lymphoma (ICML).

Patients and treatment

The trial enrolled 41 patients with treatment-naïve ENKTL, and 36 of them were evaluable.

The patients’ median age was 45 (range, 18-75), and 30.6% were female. Most patients (86.1%) had stage I/II disease, 13.9% had an ECOG performance status of 2 or greater, and 41.7% had an IPI score of 2 or greater.

The GAD-M regimen consisted of:

• Gemcitabine given at 1000 mg/m² via intravenous drip on days 1 and 8
• PEG-asparaginase given at 2500 U/m² intramuscularly on day 1
• Dexamethasone given at 20 mg via intravenous drip on days 1 to 3
• Methotrexate given at 3000 mg/m² via continuous, 12-hour infusion on day 1.

The regimen was repeated every 3 weeks.

For patients with stage I/II disease, 2 to 4 cycles of the GAD-M regimen was followed by extensive involved-field radiotherapy and an additional 2 to 4 cycles. For patients with stage III/IV disease, GAD-M was repeated for 6 cycles.

Response and survival

The ORR was 94.4%, both after 2 cycles of GAD-M and after 6 cycles. The CR rate was 50% after 2 cycles and 83.3% after 6 cycles.

In patients with stage I/II disease, the ORR was 100% after 2 cycles and 6 cycles. The CR rate was 54.8% after 2 cycles and 90.3% after 6 cycles.

In patients with stage III/IV disease, the ORR was 60% after 2 cycles and 6 cycles. The CR rate was 20% after 2 cycles and 40% after 6 cycles.

At median follow-up of 23.3 months, the estimated 3-year progression-free survival (PFS) was 72.1%, and the overall survival (OS) was 76.3%.

For patients with stage I/II disease, the PFS was 77.3%, and the OS was 79.3%. For patients with stage III/IV disease, the PFS was 40%, and the OS was 60%.

Safety

Hematologic adverse events (AEs) included anemia (97.2% total, 52.8% grade 3/4), leukocytopenia (94.4%, 27.8% grade 3/4), neutropenia (88.9%, 5.6% grade 3), and thrombocytopenia (47.2%, 13.9% grade 3/4).

Non-hematologic AEs included hypoalbuminemia (100%, 5.6% grade 3), increased transaminases (88.9%, 5.6% grade 3), hyperbilirubinemia (52.8%, 11.1% grade 3), decreased fibrinogen (19.4%, 11.1% grade 4), vomiting (13.9%, 2.8% grade 5), increased creatinine (8.3%, 2.8% grade 3), and abdominal pain (5.6% grade 1).

The grade 5 treatment-related AE occurred in a 61-year-old man. He died of electrolyte disorders caused by severe vomiting.

on Malignant Lymphoma

LUGANO, SWITZERLAND—A 4-drug regimen has demonstrated efficacy in a phase 2 trial of patients with treatment-naïve extranodal natural killer/T-cell lymphoma (ENKTL).

Treatment with gemcitabine, PEG-asparaginase, dexamethasone, and methotrexate (GAD-M) produced a 94% overall response rate (ORR) and an 83% complete response (CR) rate in this trial.

Responses and survival rates were higher in patients with stage I/II disease, who also received radiotherapy, than in patients with stage III/IV disease.

Grade 1/2 toxicities were frequent, but there were few grade 3/4 non-hematologic toxicities. One patient died of treatment-related toxicity.

Zhiming Li, of Sun Yet-sen University Cancer Center in Guangzhou, China, presented these results at the 14th International Conference on Malignant Lymphoma (ICML).

Patients and treatment

The trial enrolled 41 patients with treatment-naïve ENKTL, and 36 of them were evaluable.

The patients’ median age was 45 (range, 18-75), and 30.6% were female. Most patients (86.1%) had stage I/II disease, 13.9% had an ECOG performance status of 2 or greater, and 41.7% had an IPI score of 2 or greater.

The GAD-M regimen consisted of:

• Gemcitabine given at 1000 mg/m² via intravenous drip on days 1 and 8
• PEG-asparaginase given at 2500 U/m² intramuscularly on day 1
• Dexamethasone given at 20 mg via intravenous drip on days 1 to 3
• Methotrexate given at 3000 mg/m² via continuous, 12-hour infusion on day 1.

The regimen was repeated every 3 weeks.

For patients with stage I/II disease, 2 to 4 cycles of the GAD-M regimen was followed by extensive involved-field radiotherapy and an additional 2 to 4 cycles. For patients with stage III/IV disease, GAD-M was repeated for 6 cycles.

Response and survival

The ORR was 94.4%, both after 2 cycles of GAD-M and after 6 cycles. The CR rate was 50% after 2 cycles and 83.3% after 6 cycles.

In patients with stage I/II disease, the ORR was 100% after 2 cycles and 6 cycles. The CR rate was 54.8% after 2 cycles and 90.3% after 6 cycles.

In patients with stage III/IV disease, the ORR was 60% after 2 cycles and 6 cycles. The CR rate was 20% after 2 cycles and 40% after 6 cycles.

At median follow-up of 23.3 months, the estimated 3-year progression-free survival (PFS) was 72.1%, and the overall survival (OS) was 76.3%.

For patients with stage I/II disease, the PFS was 77.3%, and the OS was 79.3%. For patients with stage III/IV disease, the PFS was 40%, and the OS was 60%.

Safety

Hematologic adverse events (AEs) included anemia (97.2% total, 52.8% grade 3/4), leukocytopenia (94.4%, 27.8% grade 3/4), neutropenia (88.9%, 5.6% grade 3), and thrombocytopenia (47.2%, 13.9% grade 3/4).

Non-hematologic AEs included hypoalbuminemia (100%, 5.6% grade 3), increased transaminases (88.9%, 5.6% grade 3), hyperbilirubinemia (52.8%, 11.1% grade 3), decreased fibrinogen (19.4%, 11.1% grade 4), vomiting (13.9%, 2.8% grade 5), increased creatinine (8.3%, 2.8% grade 3), and abdominal pain (5.6% grade 1).

The grade 5 treatment-related AE occurred in a 61-year-old man. He died of electrolyte disorders caused by severe vomiting.

Gilles Salles, MD, PhD

The chimeric antigen receptor (CAR) T-cell therapy CTL019 produced a high response rate in a phase 2 trial of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to researchers.

An interim analysis of the JULIET trial revealed a 3-month overall response rate (ORR) of 45%.

Thirty-seven percent of patients had a complete response (CR), and all of the patients who were in CR at 3 months were still in CR at the data cutoff point.

This confirms the high response rates and durable responses observed in a previous single-center trial*, said JULIET investigator Gilles Salles, MD, PhD, of Hospices Civils de Lyon in Lyon, France.

Dr Salles presented results from JULIET at the 22nd Congress of the European Hematology Association (EHA) in Madrid, Spain (abstract LB2604).

The results were also presented at the 14th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (abstract 007).

The study was sponsored by Novartis.

Patients

JULIET enrolled 141 patients age 18 and older with relapsed/refractory DLBCL.

Forty-three patients discontinued the study before receiving CTL019—28 due to progressive disease (including 16 deaths), 9 due to an inability to manufacture CTL019, 2 due to adverse events, 1 due to investigator decision, 1 due to study withdrawal, and 1 due to protocol deviation.

Eighty-five patients were infused. The remaining 13 patients were pending infusion at the data cutoff—December 20, 2016.

The median age of the 85 infused patients was 56 (range, 24-75). Ninety-six percent of patients had DLBCL not otherwise specified. Fifty-one percent had germinal center B-cell type DLBCL.

Fifty-four percent of patients had an ECOG performance status of 0, and 46% had a status of 1. Fifty-three percent of patients had stage IV disease, and 8% had bone marrow involvement.

Forty percent of patients had 2 prior lines of antineoplastic therapy, 29% had 3, and 31% had 4 to 7 prior lines.

Forty-one percent of patients were refractory to their last therapy, and 59% had relapsed after their last therapy. Fifty-one percent of patients had prior autologous stem cell transplant.

Treatment

Seventy-six patients (89%) received bridging chemotherapy to prevent disease progression during CTL019 manufacturing. This treatment was completed 2 to 14 days prior to CTL019 infusion.

The median CTL019 cell dose was 3.1 x 10⁸ (range, 0.1-6.0 x 10⁸).

Response

Fifty-one patients were evaluated for response. The median time from infusion to data cutoff was 3.7 months.

The best ORR was 59%, with a CR rate of 43% and a partial response rate of 16%. Twelve percent of patients had stable disease, and 24% progressed.

At 3 months, the ORR was 45%. The CR rate was 37%, and the partial response rate was 8%.

“All patients in CR at 3 months remained in CR at follow-up, and the median duration of response was not reached,” Dr Salles noted.

None of the responders went on to receive a transplant.

Safety

All 85 patients were evaluated for safety. Adverse events of special interest, occurring within 8 weeks of CTL019 infusion, were:

• Cytokine release syndrome—57% all grades, 17% grade 3, 9% grade 4
• Infections—27% all grades, 12% grade 3, 1% grade 4
• Cytopenias not resolved by day 28—26% all grades, 13% grade 3, 8% grade 4
• Neurologic events—21% all grades, 9% grade 3, 4% grade 4
• Febrile neutropenia—14% all grades, 13% grade 3, 1% grade 4
• Tumor lysis syndrome—1% grade 3.

“Adverse events were reversible and effectively managed at the different centers by appropriately trained study personnel,” Dr Salles noted. “There were no CTL019-related deaths and no cerebral edema.”

*SJ Schuster et al, 2016 ASH Annual Meeting, abstract 3026

Gilles Salles, MD, PhD

The chimeric antigen receptor (CAR) T-cell therapy CTL019 produced a high response rate in a phase 2 trial of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to researchers.

An interim analysis of the JULIET trial revealed a 3-month overall response rate (ORR) of 45%.

Thirty-seven percent of patients had a complete response (CR), and all of the patients who were in CR at 3 months were still in CR at the data cutoff point.

This confirms the high response rates and durable responses observed in a previous single-center trial*, said JULIET investigator Gilles Salles, MD, PhD, of Hospices Civils de Lyon in Lyon, France.

Dr Salles presented results from JULIET at the 22nd Congress of the European Hematology Association (EHA) in Madrid, Spain (abstract LB2604).

The results were also presented at the 14th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (abstract 007).

The study was sponsored by Novartis.

Patients

JULIET enrolled 141 patients age 18 and older with relapsed/refractory DLBCL.

Forty-three patients discontinued the study before receiving CTL019—28 due to progressive disease (including 16 deaths), 9 due to an inability to manufacture CTL019, 2 due to adverse events, 1 due to investigator decision, 1 due to study withdrawal, and 1 due to protocol deviation.

Eighty-five patients were infused. The remaining 13 patients were pending infusion at the data cutoff—December 20, 2016.

The median age of the 85 infused patients was 56 (range, 24-75). Ninety-six percent of patients had DLBCL not otherwise specified. Fifty-one percent had germinal center B-cell type DLBCL.

Fifty-four percent of patients had an ECOG performance status of 0, and 46% had a status of 1. Fifty-three percent of patients had stage IV disease, and 8% had bone marrow involvement.

Forty percent of patients had 2 prior lines of antineoplastic therapy, 29% had 3, and 31% had 4 to 7 prior lines.

Forty-one percent of patients were refractory to their last therapy, and 59% had relapsed after their last therapy. Fifty-one percent of patients had prior autologous stem cell transplant.

Treatment

Seventy-six patients (89%) received bridging chemotherapy to prevent disease progression during CTL019 manufacturing. This treatment was completed 2 to 14 days prior to CTL019 infusion.

The median CTL019 cell dose was 3.1 x 10⁸ (range, 0.1-6.0 x 10⁸).

Response

Fifty-one patients were evaluated for response. The median time from infusion to data cutoff was 3.7 months.

The best ORR was 59%, with a CR rate of 43% and a partial response rate of 16%. Twelve percent of patients had stable disease, and 24% progressed.

At 3 months, the ORR was 45%. The CR rate was 37%, and the partial response rate was 8%.

“All patients in CR at 3 months remained in CR at follow-up, and the median duration of response was not reached,” Dr Salles noted.

None of the responders went on to receive a transplant.

Safety

All 85 patients were evaluated for safety. Adverse events of special interest, occurring within 8 weeks of CTL019 infusion, were:

• Cytokine release syndrome—57% all grades, 17% grade 3, 9% grade 4
• Infections—27% all grades, 12% grade 3, 1% grade 4
• Cytopenias not resolved by day 28—26% all grades, 13% grade 3, 8% grade 4
• Neurologic events—21% all grades, 9% grade 3, 4% grade 4
• Febrile neutropenia—14% all grades, 13% grade 3, 1% grade 4
• Tumor lysis syndrome—1% grade 3.

“Adverse events were reversible and effectively managed at the different centers by appropriately trained study personnel,” Dr Salles noted. “There were no CTL019-related deaths and no cerebral edema.”

*SJ Schuster et al, 2016 ASH Annual Meeting, abstract 3026

Gilles Salles, MD, PhD

The chimeric antigen receptor (CAR) T-cell therapy CTL019 produced a high response rate in a phase 2 trial of adults with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to researchers.

An interim analysis of the JULIET trial revealed a 3-month overall response rate (ORR) of 45%.

Thirty-seven percent of patients had a complete response (CR), and all of the patients who were in CR at 3 months were still in CR at the data cutoff point.

This confirms the high response rates and durable responses observed in a previous single-center trial*, said JULIET investigator Gilles Salles, MD, PhD, of Hospices Civils de Lyon in Lyon, France.

Dr Salles presented results from JULIET at the 22nd Congress of the European Hematology Association (EHA) in Madrid, Spain (abstract LB2604).

The results were also presented at the 14th International Conference on Malignant Lymphoma (ICML) in Lugano, Switzerland (abstract 007).

The study was sponsored by Novartis.

Patients

JULIET enrolled 141 patients age 18 and older with relapsed/refractory DLBCL.

Forty-three patients discontinued the study before receiving CTL019—28 due to progressive disease (including 16 deaths), 9 due to an inability to manufacture CTL019, 2 due to adverse events, 1 due to investigator decision, 1 due to study withdrawal, and 1 due to protocol deviation.

Eighty-five patients were infused. The remaining 13 patients were pending infusion at the data cutoff—December 20, 2016.

The median age of the 85 infused patients was 56 (range, 24-75). Ninety-six percent of patients had DLBCL not otherwise specified. Fifty-one percent had germinal center B-cell type DLBCL.

Fifty-four percent of patients had an ECOG performance status of 0, and 46% had a status of 1. Fifty-three percent of patients had stage IV disease, and 8% had bone marrow involvement.

Forty percent of patients had 2 prior lines of antineoplastic therapy, 29% had 3, and 31% had 4 to 7 prior lines.

Forty-one percent of patients were refractory to their last therapy, and 59% had relapsed after their last therapy. Fifty-one percent of patients had prior autologous stem cell transplant.

Treatment

Seventy-six patients (89%) received bridging chemotherapy to prevent disease progression during CTL019 manufacturing. This treatment was completed 2 to 14 days prior to CTL019 infusion.

The median CTL019 cell dose was 3.1 x 10⁸ (range, 0.1-6.0 x 10⁸).

Response

Fifty-one patients were evaluated for response. The median time from infusion to data cutoff was 3.7 months.

The best ORR was 59%, with a CR rate of 43% and a partial response rate of 16%. Twelve percent of patients had stable disease, and 24% progressed.

At 3 months, the ORR was 45%. The CR rate was 37%, and the partial response rate was 8%.

“All patients in CR at 3 months remained in CR at follow-up, and the median duration of response was not reached,” Dr Salles noted.

None of the responders went on to receive a transplant.

Safety

All 85 patients were evaluated for safety. Adverse events of special interest, occurring within 8 weeks of CTL019 infusion, were:

• Cytokine release syndrome—57% all grades, 17% grade 3, 9% grade 4
• Infections—27% all grades, 12% grade 3, 1% grade 4
• Cytopenias not resolved by day 28—26% all grades, 13% grade 3, 8% grade 4
• Neurologic events—21% all grades, 9% grade 3, 4% grade 4
• Febrile neutropenia—14% all grades, 13% grade 3, 1% grade 4
• Tumor lysis syndrome—1% grade 3.

“Adverse events were reversible and effectively managed at the different centers by appropriately trained study personnel,” Dr Salles noted. “There were no CTL019-related deaths and no cerebral edema.”

*SJ Schuster et al, 2016 ASH Annual Meeting, abstract 3026

Micrograph showing CLL

LUGANO, SWITZERLAND—Results of a phase 1 study suggest a 2-drug combination may be safe and effective in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and follicular lymphoma (FL).

The ongoing study is a test of the BTK inhibitor BGB-3111 and the anti-CD20 antibody obinutuzumab.

The overall response rate (ORR) with this combination was 81% in the entire study population, 89% in treatment-naïve CLL/SLL patients, 92% in relapsed/refractory CLL/SLL patients, and 73% in relapsed/refractory FL patients.

The rate of serious adverse events (AEs) was 24% in both CLL/SLL and FL patients.

These results were presented at the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by BeiGene, Ltd.

“This clinical trial is supported by preclinical work suggesting that BGB-3111 may combine well with antibodies that rely on antibody-dependent cell-mediated cytotoxicity, such as obinutuzumab, because of less off-target inhibition of interleukin-2-inducible T-cell kinase,” said study investigator Constantine Tam, MD, of St. Vincent’s Hospital in Melbourne, Australia.

“The preliminary clinical results to date suggest that the combination is well tolerated and highly active in patients with CLL or SLL and FL. Complete responses have already been observed in patients with both disease types, including CLL or SLL patients with high-risk features, despite a very short follow-up time.”

The trial consists of a dose-escalation phase and a dose-expansion phase in disease-specific cohorts, which include treatment-naive or relapsed/refractory CLL/SLL and relapsed/refractory FL.

The dose-escalation component is testing BGB-3111 at 320 mg once daily or 160 mg twice daily in 28-day cycles, in combination with obinutuzumab. Obinutuzumab is administered in line with standard CLL dosing (3 loading doses of 1000 mg weekly, followed by 1000 mg on day 1 of cycles 2 to 6).

The ongoing dose-expansion component is testing doses of BGB-3111 at 160 mg twice daily with the same obinutuzumab schedule.

As of the data cutoff (March 31, 2017), 45 patients with CLL/SLL and 17 patients with FL were enrolled in the trial.

Patient characteristics

The median age was 68 (range, 28-82) in the CLL/SLL patients and 56 (range, 41-86) in the FL patients.

ECOG performance status was 0 in 42% of CLL/SLL patients, 1 in 56% of these patients, and 2 in 2%. ECOG performance status was 0 in 82% of FL patients, 1 in 12% of these patients, and 2 in 6%.

Twenty CLL/SLL patients were treatment-naïve, and 25 had relapsed/refractory disease. All 17 FL patients had relapsed/refractory disease.

The median number of prior therapies was 1 (range, 1-4) in the relapsed/refractory CLL/SLL patients and 3 (range, 1-7) in the FL patients.

Safety

At the time of the data cutoff, BGB-3111 was deemed well tolerated in patients with CLL/SLL and FL.

The most frequent AEs of any cause occurring in at least 15% of patients with CLL/SLL were petechiae/purpura/contusion (33%), neutropenia (31%), thrombocytopenia (22%), fatigue (18%), pyrexia (18%), upper respiratory tract infection (18%), and diarrhea (16%).

Most of these events were grade 1/2. The exceptions were grade 3/4 neutropenia (20%) and grade 3/4 thrombocytopenia (4%).

The most frequent AEs in FL patients were petechiae/purpura/contusion (35%), fatigue (29%), cough (18%), diarrhea (18%), dizziness (18%), headache (18%), insomnia (18%), nausea (18%), and upper respiratory tract infection (18%). All of these events were grade 1/2.

Serious AEs occurred in 24% of both the CLL/SLL patients and the FL patients.

Infusion-related reactions occurred in 24% of CLL/SLL patients and 6% of FL patients. Nearly all cases were grade 1/2. The exception was 1 grade 4 case in a CLL/SLL patient.

There were no cases of serious hemorrhage (≥ grade 3 hemorrhage or central nervous system hemorrhage of any grade) or atrial fibrillation.

One patient discontinued treatment due to an AE—squamous cell carcinoma. This patient had a prior history of squamous cell carcinoma.

Efficacy

At the time of the data cutoff, 43 patients with CLL/SLL (18 treatment-naive, 25 relapsed/refractory) and 15 patients with relapsed/refractory FL had greater than 12 weeks of follow-up and were evaluable for efficacy.

In treatment-naive CLL/SLL, after a median follow-up of 7.0 months (range, 2.8–11.8 months), the ORR was 89%. The complete response (CR) rate was 22%, the rate of partial response (PR) was 67%, and the rate of stable disease (SD) was 11%.

In relapsed/refractory CLL/SLL, at a median follow-up of 8.0 months (range, 3.8–14.0 months) the ORR was 92%. The CR rate was 16%, the PR rate was 76%, and 4% of patients had SD.

One patient (4%) with relapsed/refractory CLL/SLL had progressive disease (Richter’s transformation).

In relapsed/refractory FL, at a median follow-up of 6.2 months (range, 1.2–10.7 months), the ORR was 73%. The CR rate was 33%, the PR rate was 40%, and 13% of patients had SD.

Two patients (13%) with relapsed/refractory FL had progressive disease.

On the basis of these data, BeiGene plans to expand its global registrational program for BGB-3111 to include a phase 2 trial of BGB-3111 in combination with obinutuzumab compared to obinutuzumab alone in patients with relapsed/refractory FL.

The company is also planning a phase 3 trial comparing BGB-3111 with bendamustine plus rituximab in patients with treatment-naive CLL.

Micrograph showing CLL

LUGANO, SWITZERLAND—Results of a phase 1 study suggest a 2-drug combination may be safe and effective in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and follicular lymphoma (FL).

The ongoing study is a test of the BTK inhibitor BGB-3111 and the anti-CD20 antibody obinutuzumab.

The overall response rate (ORR) with this combination was 81% in the entire study population, 89% in treatment-naïve CLL/SLL patients, 92% in relapsed/refractory CLL/SLL patients, and 73% in relapsed/refractory FL patients.

The rate of serious adverse events (AEs) was 24% in both CLL/SLL and FL patients.

These results were presented at the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by BeiGene, Ltd.

“This clinical trial is supported by preclinical work suggesting that BGB-3111 may combine well with antibodies that rely on antibody-dependent cell-mediated cytotoxicity, such as obinutuzumab, because of less off-target inhibition of interleukin-2-inducible T-cell kinase,” said study investigator Constantine Tam, MD, of St. Vincent’s Hospital in Melbourne, Australia.

“The preliminary clinical results to date suggest that the combination is well tolerated and highly active in patients with CLL or SLL and FL. Complete responses have already been observed in patients with both disease types, including CLL or SLL patients with high-risk features, despite a very short follow-up time.”

The trial consists of a dose-escalation phase and a dose-expansion phase in disease-specific cohorts, which include treatment-naive or relapsed/refractory CLL/SLL and relapsed/refractory FL.

The dose-escalation component is testing BGB-3111 at 320 mg once daily or 160 mg twice daily in 28-day cycles, in combination with obinutuzumab. Obinutuzumab is administered in line with standard CLL dosing (3 loading doses of 1000 mg weekly, followed by 1000 mg on day 1 of cycles 2 to 6).

The ongoing dose-expansion component is testing doses of BGB-3111 at 160 mg twice daily with the same obinutuzumab schedule.

As of the data cutoff (March 31, 2017), 45 patients with CLL/SLL and 17 patients with FL were enrolled in the trial.

Patient characteristics

The median age was 68 (range, 28-82) in the CLL/SLL patients and 56 (range, 41-86) in the FL patients.

ECOG performance status was 0 in 42% of CLL/SLL patients, 1 in 56% of these patients, and 2 in 2%. ECOG performance status was 0 in 82% of FL patients, 1 in 12% of these patients, and 2 in 6%.

Twenty CLL/SLL patients were treatment-naïve, and 25 had relapsed/refractory disease. All 17 FL patients had relapsed/refractory disease.

The median number of prior therapies was 1 (range, 1-4) in the relapsed/refractory CLL/SLL patients and 3 (range, 1-7) in the FL patients.

Safety

At the time of the data cutoff, BGB-3111 was deemed well tolerated in patients with CLL/SLL and FL.

The most frequent AEs of any cause occurring in at least 15% of patients with CLL/SLL were petechiae/purpura/contusion (33%), neutropenia (31%), thrombocytopenia (22%), fatigue (18%), pyrexia (18%), upper respiratory tract infection (18%), and diarrhea (16%).

Most of these events were grade 1/2. The exceptions were grade 3/4 neutropenia (20%) and grade 3/4 thrombocytopenia (4%).

The most frequent AEs in FL patients were petechiae/purpura/contusion (35%), fatigue (29%), cough (18%), diarrhea (18%), dizziness (18%), headache (18%), insomnia (18%), nausea (18%), and upper respiratory tract infection (18%). All of these events were grade 1/2.

Serious AEs occurred in 24% of both the CLL/SLL patients and the FL patients.

Infusion-related reactions occurred in 24% of CLL/SLL patients and 6% of FL patients. Nearly all cases were grade 1/2. The exception was 1 grade 4 case in a CLL/SLL patient.

There were no cases of serious hemorrhage (≥ grade 3 hemorrhage or central nervous system hemorrhage of any grade) or atrial fibrillation.

One patient discontinued treatment due to an AE—squamous cell carcinoma. This patient had a prior history of squamous cell carcinoma.

Efficacy

At the time of the data cutoff, 43 patients with CLL/SLL (18 treatment-naive, 25 relapsed/refractory) and 15 patients with relapsed/refractory FL had greater than 12 weeks of follow-up and were evaluable for efficacy.

In treatment-naive CLL/SLL, after a median follow-up of 7.0 months (range, 2.8–11.8 months), the ORR was 89%. The complete response (CR) rate was 22%, the rate of partial response (PR) was 67%, and the rate of stable disease (SD) was 11%.

In relapsed/refractory CLL/SLL, at a median follow-up of 8.0 months (range, 3.8–14.0 months) the ORR was 92%. The CR rate was 16%, the PR rate was 76%, and 4% of patients had SD.

One patient (4%) with relapsed/refractory CLL/SLL had progressive disease (Richter’s transformation).

In relapsed/refractory FL, at a median follow-up of 6.2 months (range, 1.2–10.7 months), the ORR was 73%. The CR rate was 33%, the PR rate was 40%, and 13% of patients had SD.

Two patients (13%) with relapsed/refractory FL had progressive disease.

On the basis of these data, BeiGene plans to expand its global registrational program for BGB-3111 to include a phase 2 trial of BGB-3111 in combination with obinutuzumab compared to obinutuzumab alone in patients with relapsed/refractory FL.

The company is also planning a phase 3 trial comparing BGB-3111 with bendamustine plus rituximab in patients with treatment-naive CLL.

Micrograph showing CLL

LUGANO, SWITZERLAND—Results of a phase 1 study suggest a 2-drug combination may be safe and effective in patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) and follicular lymphoma (FL).

The ongoing study is a test of the BTK inhibitor BGB-3111 and the anti-CD20 antibody obinutuzumab.

The overall response rate (ORR) with this combination was 81% in the entire study population, 89% in treatment-naïve CLL/SLL patients, 92% in relapsed/refractory CLL/SLL patients, and 73% in relapsed/refractory FL patients.

The rate of serious adverse events (AEs) was 24% in both CLL/SLL and FL patients.

These results were presented at the 14th International Conference on Malignant Lymphoma (ICML). The research was sponsored by BeiGene, Ltd.

“This clinical trial is supported by preclinical work suggesting that BGB-3111 may combine well with antibodies that rely on antibody-dependent cell-mediated cytotoxicity, such as obinutuzumab, because of less off-target inhibition of interleukin-2-inducible T-cell kinase,” said study investigator Constantine Tam, MD, of St. Vincent’s Hospital in Melbourne, Australia.

“The preliminary clinical results to date suggest that the combination is well tolerated and highly active in patients with CLL or SLL and FL. Complete responses have already been observed in patients with both disease types, including CLL or SLL patients with high-risk features, despite a very short follow-up time.”

The trial consists of a dose-escalation phase and a dose-expansion phase in disease-specific cohorts, which include treatment-naive or relapsed/refractory CLL/SLL and relapsed/refractory FL.

The dose-escalation component is testing BGB-3111 at 320 mg once daily or 160 mg twice daily in 28-day cycles, in combination with obinutuzumab. Obinutuzumab is administered in line with standard CLL dosing (3 loading doses of 1000 mg weekly, followed by 1000 mg on day 1 of cycles 2 to 6).

The ongoing dose-expansion component is testing doses of BGB-3111 at 160 mg twice daily with the same obinutuzumab schedule.

As of the data cutoff (March 31, 2017), 45 patients with CLL/SLL and 17 patients with FL were enrolled in the trial.

Patient characteristics

The median age was 68 (range, 28-82) in the CLL/SLL patients and 56 (range, 41-86) in the FL patients.

ECOG performance status was 0 in 42% of CLL/SLL patients, 1 in 56% of these patients, and 2 in 2%. ECOG performance status was 0 in 82% of FL patients, 1 in 12% of these patients, and 2 in 6%.

Twenty CLL/SLL patients were treatment-naïve, and 25 had relapsed/refractory disease. All 17 FL patients had relapsed/refractory disease.

The median number of prior therapies was 1 (range, 1-4) in the relapsed/refractory CLL/SLL patients and 3 (range, 1-7) in the FL patients.

Safety

At the time of the data cutoff, BGB-3111 was deemed well tolerated in patients with CLL/SLL and FL.

The most frequent AEs of any cause occurring in at least 15% of patients with CLL/SLL were petechiae/purpura/contusion (33%), neutropenia (31%), thrombocytopenia (22%), fatigue (18%), pyrexia (18%), upper respiratory tract infection (18%), and diarrhea (16%).

Most of these events were grade 1/2. The exceptions were grade 3/4 neutropenia (20%) and grade 3/4 thrombocytopenia (4%).

The most frequent AEs in FL patients were petechiae/purpura/contusion (35%), fatigue (29%), cough (18%), diarrhea (18%), dizziness (18%), headache (18%), insomnia (18%), nausea (18%), and upper respiratory tract infection (18%). All of these events were grade 1/2.

Serious AEs occurred in 24% of both the CLL/SLL patients and the FL patients.

Infusion-related reactions occurred in 24% of CLL/SLL patients and 6% of FL patients. Nearly all cases were grade 1/2. The exception was 1 grade 4 case in a CLL/SLL patient.

There were no cases of serious hemorrhage (≥ grade 3 hemorrhage or central nervous system hemorrhage of any grade) or atrial fibrillation.

One patient discontinued treatment due to an AE—squamous cell carcinoma. This patient had a prior history of squamous cell carcinoma.

Efficacy

At the time of the data cutoff, 43 patients with CLL/SLL (18 treatment-naive, 25 relapsed/refractory) and 15 patients with relapsed/refractory FL had greater than 12 weeks of follow-up and were evaluable for efficacy.

In treatment-naive CLL/SLL, after a median follow-up of 7.0 months (range, 2.8–11.8 months), the ORR was 89%. The complete response (CR) rate was 22%, the rate of partial response (PR) was 67%, and the rate of stable disease (SD) was 11%.

In relapsed/refractory CLL/SLL, at a median follow-up of 8.0 months (range, 3.8–14.0 months) the ORR was 92%. The CR rate was 16%, the PR rate was 76%, and 4% of patients had SD.

One patient (4%) with relapsed/refractory CLL/SLL had progressive disease (Richter’s transformation).

In relapsed/refractory FL, at a median follow-up of 6.2 months (range, 1.2–10.7 months), the ORR was 73%. The CR rate was 33%, the PR rate was 40%, and 13% of patients had SD.

Two patients (13%) with relapsed/refractory FL had progressive disease.

On the basis of these data, BeiGene plans to expand its global registrational program for BGB-3111 to include a phase 2 trial of BGB-3111 in combination with obinutuzumab compared to obinutuzumab alone in patients with relapsed/refractory FL.

The company is also planning a phase 3 trial comparing BGB-3111 with bendamustine plus rituximab in patients with treatment-naive CLL.

Photo from UAB Hospital

MADRID—Results of a phase 2 study have shown that luspatercept can produce sustained increases in hemoglobin and reductions in transfusion burden in adults with β-thalassemia.

Some patients are still receiving the drug and experiencing clinical benefits beyond 24 months.

Luspatercept has been well-tolerated in these patients, producing no serious adverse events (AEs).

“Luspatercept has many characteristics that are promising . . .,” said Antonio G. Piga, MD, of Turin University in Turin, Italy.

He presented results of the phase 2 study at the 22nd Congress of the European Hematology Association (EHA) as abstract S129.

The study was sponsored by Celgene in collaboration with Acceleron Pharma.

Dr Piga presented data on 63 patients—32 of whom were transfusion-dependent (TD) and 31 of whom were non-transfusion-dependent (NTD).

For the entire study cohort, the median age was 38 (range, 20-62), 52% of patients were male, and 67% had undergone a splenectomy.

In the NTD patients, the median hemoglobin at baseline was 8.5 g/dL (range, 6.5-9.8).

The TD patients received a median of 8 (range, 4-18) red blood cell (RBC) units every 12 weeks.

For the 3-month base study, patients received luspatercept at 0.2 mg/kg to 1.25 mg/kg every 3 weeks.

In the ongoing extension study, patients can receive luspatercept at 0.8 mg/kg to 1.25 mg/kg every 3 weeks for up to 5 years.

Efficacy in NTD patients

The median duration of treatment for NTD patients (n=31) was 18.6 months (range, 1.3-29.4 months; ongoing).

Over a 12-week period, 71% (22/31) of NTD patients saw at least a 1.0 g/dL increase in mean hemoglobin from baseline. Fifty-two percent (16/31) saw an increase of 1.5 g/dL or greater.

To assess quality of life in NTD patients, the researchers used FACIT-F, a 13-item questionnaire used to assess anemia-related symptoms such as fatigue and weakness.

Fifty-eight percent (7/12) of patients with a baseline FACIT-F deficit (<44 points) had improved by at least 3 points at 48 weeks.

And 86% (6/7) of patients with at least a 3-point increase in FACIT-F score had at least a 1.0 g/dL improvement in mean hemoglobin over a 12-week period.

Efficacy in TD patients

The median duration of treatment for TD patients was 14.2 months (range, 0.7-27.2 months, ongoing).

Seventy-eight percent (25/32) of these patients had at least a 20% reduction in RBC units transfused from 12 weeks pre-treatment to any 12-week interval on treatment. Sixty-nine percent (22/32) had at least a 33% reduction at any 12-week interval.

Fifty percent of patients (12/24) who received an estimated 6 to 20 RBC units every 24 weeks achieved a reduction in transfusion burden from baseline of at least 33% in the fixed 12-week interval from weeks 13 to 24.

Forty-six percent (11/24) achieved a reduction in transfusion burden from baseline of at least 33% in the interval from weeks 37 to 48.

Safety

The most common AEs possibly or probably related to luspatercept were bone pain (38%), headache (28%), myalgia (22%), arthralgia (19%), musculoskeletal pain (17%), asthenia (14%), injection site pain (13%), and back pain (11%).

Most AEs were grade 1 or 2 in severity. Treatment-related grade 3 AEs included bone pain (n=3), asthenia (n=2), and headache (n=1).

Dr Piga said these results support an ongoing phase 3 study of luspatercept in regularly transfused patients with β-thalassemia (BELIEVE, NCT02604433), which recently completed enrollment.

Photo from UAB Hospital

MADRID—Results of a phase 2 study have shown that luspatercept can produce sustained increases in hemoglobin and reductions in transfusion burden in adults with β-thalassemia.

Some patients are still receiving the drug and experiencing clinical benefits beyond 24 months.

Luspatercept has been well-tolerated in these patients, producing no serious adverse events (AEs).

“Luspatercept has many characteristics that are promising . . .,” said Antonio G. Piga, MD, of Turin University in Turin, Italy.

He presented results of the phase 2 study at the 22nd Congress of the European Hematology Association (EHA) as abstract S129.

The study was sponsored by Celgene in collaboration with Acceleron Pharma.

Dr Piga presented data on 63 patients—32 of whom were transfusion-dependent (TD) and 31 of whom were non-transfusion-dependent (NTD).

For the entire study cohort, the median age was 38 (range, 20-62), 52% of patients were male, and 67% had undergone a splenectomy.

In the NTD patients, the median hemoglobin at baseline was 8.5 g/dL (range, 6.5-9.8).

The TD patients received a median of 8 (range, 4-18) red blood cell (RBC) units every 12 weeks.

For the 3-month base study, patients received luspatercept at 0.2 mg/kg to 1.25 mg/kg every 3 weeks.

In the ongoing extension study, patients can receive luspatercept at 0.8 mg/kg to 1.25 mg/kg every 3 weeks for up to 5 years.

Efficacy in NTD patients

The median duration of treatment for NTD patients (n=31) was 18.6 months (range, 1.3-29.4 months; ongoing).

Over a 12-week period, 71% (22/31) of NTD patients saw at least a 1.0 g/dL increase in mean hemoglobin from baseline. Fifty-two percent (16/31) saw an increase of 1.5 g/dL or greater.

To assess quality of life in NTD patients, the researchers used FACIT-F, a 13-item questionnaire used to assess anemia-related symptoms such as fatigue and weakness.

Fifty-eight percent (7/12) of patients with a baseline FACIT-F deficit (<44 points) had improved by at least 3 points at 48 weeks.

And 86% (6/7) of patients with at least a 3-point increase in FACIT-F score had at least a 1.0 g/dL improvement in mean hemoglobin over a 12-week period.

Efficacy in TD patients

The median duration of treatment for TD patients was 14.2 months (range, 0.7-27.2 months, ongoing).

Seventy-eight percent (25/32) of these patients had at least a 20% reduction in RBC units transfused from 12 weeks pre-treatment to any 12-week interval on treatment. Sixty-nine percent (22/32) had at least a 33% reduction at any 12-week interval.

Fifty percent of patients (12/24) who received an estimated 6 to 20 RBC units every 24 weeks achieved a reduction in transfusion burden from baseline of at least 33% in the fixed 12-week interval from weeks 13 to 24.

Forty-six percent (11/24) achieved a reduction in transfusion burden from baseline of at least 33% in the interval from weeks 37 to 48.

Safety

The most common AEs possibly or probably related to luspatercept were bone pain (38%), headache (28%), myalgia (22%), arthralgia (19%), musculoskeletal pain (17%), asthenia (14%), injection site pain (13%), and back pain (11%).

Most AEs were grade 1 or 2 in severity. Treatment-related grade 3 AEs included bone pain (n=3), asthenia (n=2), and headache (n=1).

Dr Piga said these results support an ongoing phase 3 study of luspatercept in regularly transfused patients with β-thalassemia (BELIEVE, NCT02604433), which recently completed enrollment.

Photo from UAB Hospital

MADRID—Results of a phase 2 study have shown that luspatercept can produce sustained increases in hemoglobin and reductions in transfusion burden in adults with β-thalassemia.

Some patients are still receiving the drug and experiencing clinical benefits beyond 24 months.

Luspatercept has been well-tolerated in these patients, producing no serious adverse events (AEs).

“Luspatercept has many characteristics that are promising . . .,” said Antonio G. Piga, MD, of Turin University in Turin, Italy.

He presented results of the phase 2 study at the 22nd Congress of the European Hematology Association (EHA) as abstract S129.

The study was sponsored by Celgene in collaboration with Acceleron Pharma.

Dr Piga presented data on 63 patients—32 of whom were transfusion-dependent (TD) and 31 of whom were non-transfusion-dependent (NTD).

For the entire study cohort, the median age was 38 (range, 20-62), 52% of patients were male, and 67% had undergone a splenectomy.

In the NTD patients, the median hemoglobin at baseline was 8.5 g/dL (range, 6.5-9.8).

The TD patients received a median of 8 (range, 4-18) red blood cell (RBC) units every 12 weeks.

For the 3-month base study, patients received luspatercept at 0.2 mg/kg to 1.25 mg/kg every 3 weeks.

In the ongoing extension study, patients can receive luspatercept at 0.8 mg/kg to 1.25 mg/kg every 3 weeks for up to 5 years.

Efficacy in NTD patients

The median duration of treatment for NTD patients (n=31) was 18.6 months (range, 1.3-29.4 months; ongoing).

Over a 12-week period, 71% (22/31) of NTD patients saw at least a 1.0 g/dL increase in mean hemoglobin from baseline. Fifty-two percent (16/31) saw an increase of 1.5 g/dL or greater.

To assess quality of life in NTD patients, the researchers used FACIT-F, a 13-item questionnaire used to assess anemia-related symptoms such as fatigue and weakness.

Fifty-eight percent (7/12) of patients with a baseline FACIT-F deficit (<44 points) had improved by at least 3 points at 48 weeks.

And 86% (6/7) of patients with at least a 3-point increase in FACIT-F score had at least a 1.0 g/dL improvement in mean hemoglobin over a 12-week period.

Efficacy in TD patients

The median duration of treatment for TD patients was 14.2 months (range, 0.7-27.2 months, ongoing).

Seventy-eight percent (25/32) of these patients had at least a 20% reduction in RBC units transfused from 12 weeks pre-treatment to any 12-week interval on treatment. Sixty-nine percent (22/32) had at least a 33% reduction at any 12-week interval.

Fifty percent of patients (12/24) who received an estimated 6 to 20 RBC units every 24 weeks achieved a reduction in transfusion burden from baseline of at least 33% in the fixed 12-week interval from weeks 13 to 24.

Forty-six percent (11/24) achieved a reduction in transfusion burden from baseline of at least 33% in the interval from weeks 37 to 48.

Safety

The most common AEs possibly or probably related to luspatercept were bone pain (38%), headache (28%), myalgia (22%), arthralgia (19%), musculoskeletal pain (17%), asthenia (14%), injection site pain (13%), and back pain (11%).

Most AEs were grade 1 or 2 in severity. Treatment-related grade 3 AEs included bone pain (n=3), asthenia (n=2), and headache (n=1).

Dr Piga said these results support an ongoing phase 3 study of luspatercept in regularly transfused patients with β-thalassemia (BELIEVE, NCT02604433), which recently completed enrollment.

Micrograph showing HL

LUGANO, SWITZERLAND—Nivolumab can provide long-term treatment for a broad range of adults who have relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic stem cell transplant (auto-HSCT), according to a presentation at the 14th International Conference on Malignant Lymphoma (ICML).

In the phase 2 CheckMate-205 study, cHL patients achieved durable responses regardless of the depth of response, previous exposure to brentuximab vedotin (BV), and refractoriness to prior therapies.

Researchers observed sustained progression-free survival (PFS) in patients with stable disease (SD) or better, and the safety profile of nivolumab was considered acceptable.

“Nivolumab offers a favorable treatment outcome for patients who have relapsed disease after autologous stem cell transplant,” said Michelle Fanale, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Fanale presented results from CheckMate-205 at 14-ICML. The study was sponsored by Bristol-Myers Squibb Company.

CheckMate-205 enrolled 243 adults with relapsed or refractory cHL who had undergone auto-HSCT. Patients were divided into 3 cohorts:

• Cohort A included patients who were naïve to BV (n=63)
• Cohort B included patients who received BV only after auto-HSCT (n=80)
• Cohort C included patients who received BV before and/or after auto-HSCT (n=100).

All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.

In cohort C, patients who were in complete response (CR) for 1 year were to discontinue nivolumab, but they could resume treatment with the drug if they relapsed within 2 years.

Patient characteristics

The median age was 33 (range, 18-65) in cohort A, 37 (range, 18-72) in cohort B, and 32 (range, 19-69) in cohort C.

ECOG performance status was 0 for 62% of patients in cohort A, 53% in cohort B, and 50% in cohort C. The remaining patients had a performance status of 1.

The percentage of patients with stage IV disease was 38% in cohort A, 68% in cohort B, and 61% in cohort C.

The median number of prior therapies was 2 (range, 2-8) in cohort A, 4 (range, 3-15) in cohort B, and 4 (range, 2-9) in cohort C. Fifty-nine percent, 74%, and 69% of patients, respectively, had received prior radiotherapy.

The median time from diagnosis to the first dose of nivolumab was 3.1 years (range, 1.0-30.6) in cohort A, 6.2 years (range, 1.3-25.1) in cohort B, and 3.5 years (range, 1.0-24.9) in cohort C.

The median time from auto-HSCT to the first dose of nivolumab was 1.0 years (range, 0.3-18.2) in cohort A, 3.4 years (range, 0.2-19.0) in cohort B, and 1.7 years (range, 0.2-17.0) in cohort C.

Safety

The most common drug-related adverse events (AEs) were fatigue (23% any grade, 1% grade 3/4), diarrhea (15% any grade, 1% grade 3/4), infusion-related reactions (14% any grade, <1% grade 3/4), rash (12% any grade, 1% grade 3/4), nausea (10% grade 1/2), and pruritus (10% grade 1/2).

The most common drug-related serious AEs were infusion-related reactions (2% any grade, <1% grade 3/4) and pneumonitis (1% grade 1/2).

Drug-related AEs leading to treatment discontinuation were pneumonitis (2% grade 1/2) and autoimmune hepatitis (1% grade 3/4).

There were no deaths due to drug-related AEs.

Response

The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.

CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.

Partial response (PR) was the best response for 53% of all patients, 37% of patients in cohort A, 55% in cohort B, and 61% in cohort C.

SD was the best response for 19% of all patients, 24% of patients in cohort A, 21% in cohort B, and 15% in cohort C.

In post-hoc analyses, responses were similar irrespective of BV treatment sequence.

The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, and 15 months for cohort C.

The median duration of response in patients with a CR was 20 months overall and for cohorts A and B, but it was 15 months for cohort C.

The median duration of response in patients with a PR was 13 months overall, 17 months for cohort A, 11 months for cohort B, and 13 months for cohort C.

Survival

The median PFS for all patients was 15 months (range, 11-19). The median PFS was 22 months (range, 19-not reached) for patients who achieved a CR, 15 months (range, 11-19) for those who achieved a PR, and 11 months (range, 6-18) for those who had SD.

The median PFS was 18 months (range, 11-22) for patients in cohort A, 15 months (range, 11-20) for cohort B, and 12 months (range, 11-18) for cohort C.

The median overall survival (OS) has not been reached in any of the cohorts. The 12-months OS is 92% overall, 93% in cohort A, 95% in cohort B, and 90% in cohort C.

Patient status after extended follow-up

Forty percent of all patients were still on treatment after extended follow-up, as were 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.

The most common reason for stopping treatment was disease progression—25% of cohort A, 28% of cohort B, and 24% of cohort C.

Patients also stopped treatment due to nivolumab-related toxicity—5% in cohort A, 11% in cohort B, and 7% in cohort C. Three percent, 1%, and 1%, respectively, stopped due to AEs unrelated to nivolumab.

Three percent of patients in cohort C stopped because they had attained the maximum clinical benefit, and 8% in cohort C completed treatment. This includes 7 patients who discontinued treatment because they were in CR for 1 year.

None of the patients in cohort A or B discontinued because they attained the maximum clinical benefit or because they completed treatment.

Eight percent of patients in cohort A, 10% in cohort B, and 17% in cohort C discontinued so they could proceed to HSCT.

Outcomes after allo-HSCT

Forty-four patients received allogeneic (allo-) HSCT after nivolumab. The median post-HSCT follow-up was 5.5 months (range, 0-19), and the median time from last dose of nivolumab to allo-HSCT was 1.6 months (range, 0.5-13.5).

At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 27%. The rate of grade 3-4 acute GVHD was 17%, and the rate of chronic GVHD was 10%.  At 6 months, the rates were 30%, 20%, and 15%, respectively.

The incidence of transplant-related mortality was 13% at 100 days and at 6 months.

“While there are risks, potentially, for acute GVHD and transplant-related mortality, these aren’t necessarily significantly different from what we’ve seen from other historical publications,” Dr Fanale said.

She cited data showing that the 100-day incidence of acute GVHD in cHL patients who underwent allo-HSCT ranges from 26% to 60%, and the incidence of transplant-related mortality in these patients ranges from 6% to 28%.

Micrograph showing HL

LUGANO, SWITZERLAND—Nivolumab can provide long-term treatment for a broad range of adults who have relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic stem cell transplant (auto-HSCT), according to a presentation at the 14th International Conference on Malignant Lymphoma (ICML).

In the phase 2 CheckMate-205 study, cHL patients achieved durable responses regardless of the depth of response, previous exposure to brentuximab vedotin (BV), and refractoriness to prior therapies.

Researchers observed sustained progression-free survival (PFS) in patients with stable disease (SD) or better, and the safety profile of nivolumab was considered acceptable.

“Nivolumab offers a favorable treatment outcome for patients who have relapsed disease after autologous stem cell transplant,” said Michelle Fanale, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Fanale presented results from CheckMate-205 at 14-ICML. The study was sponsored by Bristol-Myers Squibb Company.

CheckMate-205 enrolled 243 adults with relapsed or refractory cHL who had undergone auto-HSCT. Patients were divided into 3 cohorts:

• Cohort A included patients who were naïve to BV (n=63)
• Cohort B included patients who received BV only after auto-HSCT (n=80)
• Cohort C included patients who received BV before and/or after auto-HSCT (n=100).

All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.

In cohort C, patients who were in complete response (CR) for 1 year were to discontinue nivolumab, but they could resume treatment with the drug if they relapsed within 2 years.

Patient characteristics

The median age was 33 (range, 18-65) in cohort A, 37 (range, 18-72) in cohort B, and 32 (range, 19-69) in cohort C.

ECOG performance status was 0 for 62% of patients in cohort A, 53% in cohort B, and 50% in cohort C. The remaining patients had a performance status of 1.

The percentage of patients with stage IV disease was 38% in cohort A, 68% in cohort B, and 61% in cohort C.

The median number of prior therapies was 2 (range, 2-8) in cohort A, 4 (range, 3-15) in cohort B, and 4 (range, 2-9) in cohort C. Fifty-nine percent, 74%, and 69% of patients, respectively, had received prior radiotherapy.

The median time from diagnosis to the first dose of nivolumab was 3.1 years (range, 1.0-30.6) in cohort A, 6.2 years (range, 1.3-25.1) in cohort B, and 3.5 years (range, 1.0-24.9) in cohort C.

The median time from auto-HSCT to the first dose of nivolumab was 1.0 years (range, 0.3-18.2) in cohort A, 3.4 years (range, 0.2-19.0) in cohort B, and 1.7 years (range, 0.2-17.0) in cohort C.

Safety

The most common drug-related adverse events (AEs) were fatigue (23% any grade, 1% grade 3/4), diarrhea (15% any grade, 1% grade 3/4), infusion-related reactions (14% any grade, <1% grade 3/4), rash (12% any grade, 1% grade 3/4), nausea (10% grade 1/2), and pruritus (10% grade 1/2).

The most common drug-related serious AEs were infusion-related reactions (2% any grade, <1% grade 3/4) and pneumonitis (1% grade 1/2).

Drug-related AEs leading to treatment discontinuation were pneumonitis (2% grade 1/2) and autoimmune hepatitis (1% grade 3/4).

There were no deaths due to drug-related AEs.

Response

The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.

CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.

Partial response (PR) was the best response for 53% of all patients, 37% of patients in cohort A, 55% in cohort B, and 61% in cohort C.

SD was the best response for 19% of all patients, 24% of patients in cohort A, 21% in cohort B, and 15% in cohort C.

In post-hoc analyses, responses were similar irrespective of BV treatment sequence.

The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, and 15 months for cohort C.

The median duration of response in patients with a CR was 20 months overall and for cohorts A and B, but it was 15 months for cohort C.

The median duration of response in patients with a PR was 13 months overall, 17 months for cohort A, 11 months for cohort B, and 13 months for cohort C.

Survival

The median PFS for all patients was 15 months (range, 11-19). The median PFS was 22 months (range, 19-not reached) for patients who achieved a CR, 15 months (range, 11-19) for those who achieved a PR, and 11 months (range, 6-18) for those who had SD.

The median PFS was 18 months (range, 11-22) for patients in cohort A, 15 months (range, 11-20) for cohort B, and 12 months (range, 11-18) for cohort C.

The median overall survival (OS) has not been reached in any of the cohorts. The 12-months OS is 92% overall, 93% in cohort A, 95% in cohort B, and 90% in cohort C.

Patient status after extended follow-up

Forty percent of all patients were still on treatment after extended follow-up, as were 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.

The most common reason for stopping treatment was disease progression—25% of cohort A, 28% of cohort B, and 24% of cohort C.

Patients also stopped treatment due to nivolumab-related toxicity—5% in cohort A, 11% in cohort B, and 7% in cohort C. Three percent, 1%, and 1%, respectively, stopped due to AEs unrelated to nivolumab.

Three percent of patients in cohort C stopped because they had attained the maximum clinical benefit, and 8% in cohort C completed treatment. This includes 7 patients who discontinued treatment because they were in CR for 1 year.

None of the patients in cohort A or B discontinued because they attained the maximum clinical benefit or because they completed treatment.

Eight percent of patients in cohort A, 10% in cohort B, and 17% in cohort C discontinued so they could proceed to HSCT.

Outcomes after allo-HSCT

Forty-four patients received allogeneic (allo-) HSCT after nivolumab. The median post-HSCT follow-up was 5.5 months (range, 0-19), and the median time from last dose of nivolumab to allo-HSCT was 1.6 months (range, 0.5-13.5).

At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 27%. The rate of grade 3-4 acute GVHD was 17%, and the rate of chronic GVHD was 10%.  At 6 months, the rates were 30%, 20%, and 15%, respectively.

The incidence of transplant-related mortality was 13% at 100 days and at 6 months.

“While there are risks, potentially, for acute GVHD and transplant-related mortality, these aren’t necessarily significantly different from what we’ve seen from other historical publications,” Dr Fanale said.

She cited data showing that the 100-day incidence of acute GVHD in cHL patients who underwent allo-HSCT ranges from 26% to 60%, and the incidence of transplant-related mortality in these patients ranges from 6% to 28%.

Micrograph showing HL

LUGANO, SWITZERLAND—Nivolumab can provide long-term treatment for a broad range of adults who have relapsed or refractory classical Hodgkin lymphoma (cHL) after autologous hematopoietic stem cell transplant (auto-HSCT), according to a presentation at the 14th International Conference on Malignant Lymphoma (ICML).

In the phase 2 CheckMate-205 study, cHL patients achieved durable responses regardless of the depth of response, previous exposure to brentuximab vedotin (BV), and refractoriness to prior therapies.

Researchers observed sustained progression-free survival (PFS) in patients with stable disease (SD) or better, and the safety profile of nivolumab was considered acceptable.

“Nivolumab offers a favorable treatment outcome for patients who have relapsed disease after autologous stem cell transplant,” said Michelle Fanale, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Fanale presented results from CheckMate-205 at 14-ICML. The study was sponsored by Bristol-Myers Squibb Company.

CheckMate-205 enrolled 243 adults with relapsed or refractory cHL who had undergone auto-HSCT. Patients were divided into 3 cohorts:

• Cohort A included patients who were naïve to BV (n=63)
• Cohort B included patients who received BV only after auto-HSCT (n=80)
• Cohort C included patients who received BV before and/or after auto-HSCT (n=100).

All patients received nivolumab at 3 mg/kg once every 2 weeks until disease progression or unacceptable toxicity.

In cohort C, patients who were in complete response (CR) for 1 year were to discontinue nivolumab, but they could resume treatment with the drug if they relapsed within 2 years.

Patient characteristics

The median age was 33 (range, 18-65) in cohort A, 37 (range, 18-72) in cohort B, and 32 (range, 19-69) in cohort C.

ECOG performance status was 0 for 62% of patients in cohort A, 53% in cohort B, and 50% in cohort C. The remaining patients had a performance status of 1.

The percentage of patients with stage IV disease was 38% in cohort A, 68% in cohort B, and 61% in cohort C.

The median number of prior therapies was 2 (range, 2-8) in cohort A, 4 (range, 3-15) in cohort B, and 4 (range, 2-9) in cohort C. Fifty-nine percent, 74%, and 69% of patients, respectively, had received prior radiotherapy.

The median time from diagnosis to the first dose of nivolumab was 3.1 years (range, 1.0-30.6) in cohort A, 6.2 years (range, 1.3-25.1) in cohort B, and 3.5 years (range, 1.0-24.9) in cohort C.

The median time from auto-HSCT to the first dose of nivolumab was 1.0 years (range, 0.3-18.2) in cohort A, 3.4 years (range, 0.2-19.0) in cohort B, and 1.7 years (range, 0.2-17.0) in cohort C.

Safety

The most common drug-related adverse events (AEs) were fatigue (23% any grade, 1% grade 3/4), diarrhea (15% any grade, 1% grade 3/4), infusion-related reactions (14% any grade, <1% grade 3/4), rash (12% any grade, 1% grade 3/4), nausea (10% grade 1/2), and pruritus (10% grade 1/2).

The most common drug-related serious AEs were infusion-related reactions (2% any grade, <1% grade 3/4) and pneumonitis (1% grade 1/2).

Drug-related AEs leading to treatment discontinuation were pneumonitis (2% grade 1/2) and autoimmune hepatitis (1% grade 3/4).

There were no deaths due to drug-related AEs.

Response

The objective response rate was 69% overall, 65% in cohort A, 68% in cohort B, and 73% in cohort C.

CR was the best response for 16% of all patients, 29% of cohort A, 13% of cohort B, and 12% of cohort C.

Partial response (PR) was the best response for 53% of all patients, 37% of patients in cohort A, 55% in cohort B, and 61% in cohort C.

SD was the best response for 19% of all patients, 24% of patients in cohort A, 21% in cohort B, and 15% in cohort C.

In post-hoc analyses, responses were similar irrespective of BV treatment sequence.

The median duration of response was 17 months overall, 20 months for cohort A, 16 months for cohort B, and 15 months for cohort C.

The median duration of response in patients with a CR was 20 months overall and for cohorts A and B, but it was 15 months for cohort C.

The median duration of response in patients with a PR was 13 months overall, 17 months for cohort A, 11 months for cohort B, and 13 months for cohort C.

Survival

The median PFS for all patients was 15 months (range, 11-19). The median PFS was 22 months (range, 19-not reached) for patients who achieved a CR, 15 months (range, 11-19) for those who achieved a PR, and 11 months (range, 6-18) for those who had SD.

The median PFS was 18 months (range, 11-22) for patients in cohort A, 15 months (range, 11-20) for cohort B, and 12 months (range, 11-18) for cohort C.

The median overall survival (OS) has not been reached in any of the cohorts. The 12-months OS is 92% overall, 93% in cohort A, 95% in cohort B, and 90% in cohort C.

Patient status after extended follow-up

Forty percent of all patients were still on treatment after extended follow-up, as were 48% of patients in cohort A, 40% in cohort B, and 35% in cohort C.

The most common reason for stopping treatment was disease progression—25% of cohort A, 28% of cohort B, and 24% of cohort C.

Patients also stopped treatment due to nivolumab-related toxicity—5% in cohort A, 11% in cohort B, and 7% in cohort C. Three percent, 1%, and 1%, respectively, stopped due to AEs unrelated to nivolumab.

Three percent of patients in cohort C stopped because they had attained the maximum clinical benefit, and 8% in cohort C completed treatment. This includes 7 patients who discontinued treatment because they were in CR for 1 year.

None of the patients in cohort A or B discontinued because they attained the maximum clinical benefit or because they completed treatment.

Eight percent of patients in cohort A, 10% in cohort B, and 17% in cohort C discontinued so they could proceed to HSCT.

Outcomes after allo-HSCT

Forty-four patients received allogeneic (allo-) HSCT after nivolumab. The median post-HSCT follow-up was 5.5 months (range, 0-19), and the median time from last dose of nivolumab to allo-HSCT was 1.6 months (range, 0.5-13.5).

At 100 days, the rate of grade 2-4 acute graft-vs-host disease (GVHD) was 27%. The rate of grade 3-4 acute GVHD was 17%, and the rate of chronic GVHD was 10%.  At 6 months, the rates were 30%, 20%, and 15%, respectively.

The incidence of transplant-related mortality was 13% at 100 days and at 6 months.

“While there are risks, potentially, for acute GVHD and transplant-related mortality, these aren’t necessarily significantly different from what we’ve seen from other historical publications,” Dr Fanale said.

She cited data showing that the 100-day incidence of acute GVHD in cHL patients who underwent allo-HSCT ranges from 26% to 60%, and the incidence of transplant-related mortality in these patients ranges from 6% to 28%.

Congress of EHA

An all-oral treatment regimen can produce deep and durable responses in patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 22nd Congress of the European Hematology Association (EHA).

In a phase 1/2 study, patients with newly diagnosed MM received treatment with ixazomib, lenalidomide, and dexamethasone for up to 12 cycles, followed by maintenance with ixazomib alone.

The overall response rate was 88% for the entire cohort and 80% among patients who did not proceed to transplant.

The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to transplant.

Most patients did not complete all 12 cycles of induction, but 38% proceeded to maintenance, and 12% remain on study treatment at a median follow-up of 56 months.

Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota, presented these results at the EHA Congress as abstract S408. The research was sponsored by Millennium Pharmaceuticals, Inc., a subsidiary of Takeda Pharmaceutical Company Limited.

Patients

The trial included 65 patients. Their median age was 66 (range, 34-86), and 55% were male. Eight percent of patients had high-risk cytogenetics.

ECOG performance status was 0 for 43% of patients, 1 for 52%, and 2 for 5%. ISS stage was 1 for 43% of patients, 2 for 43%, and 3 for 14%.

Treatment

Patients received ixazomib (1.68 - 3.95 mg/m² in phase 1 and 4.0 mg in phase 2 on days 1, 8, and 15) plus lenalidomide (25 mg on days 1-21), and dexamethasone (40 mg on days 1, 8, 15, and 22) for up to twelve, 28-day cycles. Patients could then receive ixazomib maintenance until disease progression or unacceptable toxicity.

Twenty-three patients (35%) discontinued induction to undergo hematopoietic stem cell transplant (HSCT).

Thirty-seven patients discontinued study treatment for other reasons—17 of them during induction. Twenty-one patients discontinued due to progressive disease, 9 due to adverse events (AEs), 5 due to patient withdrawal, 1 due to unsatisfactory response, and 1 due to other reasons.

Twenty-five patients completed induction and went on to receive ixazomib maintenance. Five patients remain on study treatment.

Safety

Seventy-eight percent of patients had a grade 3 or higher AE, 46% had a serious AE, 57% had an AE leading to dose reduction, and 15% had an AE leading to discontinuation of any of the study drugs. There were 2 on-study deaths.

The most common grade 3 or higher AEs were neutropenia, thrombocytopenia, diarrhea, back pain, vomiting, nausea, peripheral neuropathy, and rashes/eruptions/exanthems.

Efficacy

The overall response rate was 88% for the entire cohort and 80% among patients who did not go on to receive HSCT.

The complete response (CR) rates were 23% and 32%, respectively. Thirty four percent and 32%, respectively, had a very good partial response (VGPR). And 30% and 17%, respectively, had a partial response (PR).

Thirty-two percent of patients who received maintenance (n=8) had an improvement in their response during the maintenance phase.  Two patients went from a VGPR to a stringent CR, 3 went from a VGPR to a CR, 2 went from a VGPR to a near CR, and 1 went from a PR to a VGPR.

Sixteen patients were evaluated for minimal residual disease (MRD). Of the patients with a stringent CR/CR, 89% (8/9) were MRD-negative.

The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to HSCT. The 4-year overall survival rate was 84% and 82%, respectively.

“Long-term follow-up, a median follow-up of 56 months, with the combination of ixazomib, lenalidomide, and dexamethasone demonstrates that this is an efficacious regimen for newly diagnosed myeloma patients, with excellent tolerability, and something that can be maintained for a long period of time,” Dr Kumar said. “These results form the basis for an ongoing phase 3 program.”

Congress of EHA

An all-oral treatment regimen can produce deep and durable responses in patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 22nd Congress of the European Hematology Association (EHA).

In a phase 1/2 study, patients with newly diagnosed MM received treatment with ixazomib, lenalidomide, and dexamethasone for up to 12 cycles, followed by maintenance with ixazomib alone.

The overall response rate was 88% for the entire cohort and 80% among patients who did not proceed to transplant.

The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to transplant.

Most patients did not complete all 12 cycles of induction, but 38% proceeded to maintenance, and 12% remain on study treatment at a median follow-up of 56 months.

Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota, presented these results at the EHA Congress as abstract S408. The research was sponsored by Millennium Pharmaceuticals, Inc., a subsidiary of Takeda Pharmaceutical Company Limited.

Patients

The trial included 65 patients. Their median age was 66 (range, 34-86), and 55% were male. Eight percent of patients had high-risk cytogenetics.

ECOG performance status was 0 for 43% of patients, 1 for 52%, and 2 for 5%. ISS stage was 1 for 43% of patients, 2 for 43%, and 3 for 14%.

Treatment

Patients received ixazomib (1.68 - 3.95 mg/m² in phase 1 and 4.0 mg in phase 2 on days 1, 8, and 15) plus lenalidomide (25 mg on days 1-21), and dexamethasone (40 mg on days 1, 8, 15, and 22) for up to twelve, 28-day cycles. Patients could then receive ixazomib maintenance until disease progression or unacceptable toxicity.

Twenty-three patients (35%) discontinued induction to undergo hematopoietic stem cell transplant (HSCT).

Thirty-seven patients discontinued study treatment for other reasons—17 of them during induction. Twenty-one patients discontinued due to progressive disease, 9 due to adverse events (AEs), 5 due to patient withdrawal, 1 due to unsatisfactory response, and 1 due to other reasons.

Twenty-five patients completed induction and went on to receive ixazomib maintenance. Five patients remain on study treatment.

Safety

Seventy-eight percent of patients had a grade 3 or higher AE, 46% had a serious AE, 57% had an AE leading to dose reduction, and 15% had an AE leading to discontinuation of any of the study drugs. There were 2 on-study deaths.

The most common grade 3 or higher AEs were neutropenia, thrombocytopenia, diarrhea, back pain, vomiting, nausea, peripheral neuropathy, and rashes/eruptions/exanthems.

Efficacy

The overall response rate was 88% for the entire cohort and 80% among patients who did not go on to receive HSCT.

The complete response (CR) rates were 23% and 32%, respectively. Thirty four percent and 32%, respectively, had a very good partial response (VGPR). And 30% and 17%, respectively, had a partial response (PR).

Thirty-two percent of patients who received maintenance (n=8) had an improvement in their response during the maintenance phase.  Two patients went from a VGPR to a stringent CR, 3 went from a VGPR to a CR, 2 went from a VGPR to a near CR, and 1 went from a PR to a VGPR.

Sixteen patients were evaluated for minimal residual disease (MRD). Of the patients with a stringent CR/CR, 89% (8/9) were MRD-negative.

The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to HSCT. The 4-year overall survival rate was 84% and 82%, respectively.

“Long-term follow-up, a median follow-up of 56 months, with the combination of ixazomib, lenalidomide, and dexamethasone demonstrates that this is an efficacious regimen for newly diagnosed myeloma patients, with excellent tolerability, and something that can be maintained for a long period of time,” Dr Kumar said. “These results form the basis for an ongoing phase 3 program.”

Congress of EHA

An all-oral treatment regimen can produce deep and durable responses in patients with newly diagnosed multiple myeloma (MM), according to a speaker at the 22nd Congress of the European Hematology Association (EHA).

In a phase 1/2 study, patients with newly diagnosed MM received treatment with ixazomib, lenalidomide, and dexamethasone for up to 12 cycles, followed by maintenance with ixazomib alone.

The overall response rate was 88% for the entire cohort and 80% among patients who did not proceed to transplant.

The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to transplant.

Most patients did not complete all 12 cycles of induction, but 38% proceeded to maintenance, and 12% remain on study treatment at a median follow-up of 56 months.

Shaji Kumar, MD, of the Mayo Clinic in Rochester, Minnesota, presented these results at the EHA Congress as abstract S408. The research was sponsored by Millennium Pharmaceuticals, Inc., a subsidiary of Takeda Pharmaceutical Company Limited.

Patients

The trial included 65 patients. Their median age was 66 (range, 34-86), and 55% were male. Eight percent of patients had high-risk cytogenetics.

ECOG performance status was 0 for 43% of patients, 1 for 52%, and 2 for 5%. ISS stage was 1 for 43% of patients, 2 for 43%, and 3 for 14%.

Treatment

Patients received ixazomib (1.68 - 3.95 mg/m² in phase 1 and 4.0 mg in phase 2 on days 1, 8, and 15) plus lenalidomide (25 mg on days 1-21), and dexamethasone (40 mg on days 1, 8, 15, and 22) for up to twelve, 28-day cycles. Patients could then receive ixazomib maintenance until disease progression or unacceptable toxicity.

Twenty-three patients (35%) discontinued induction to undergo hematopoietic stem cell transplant (HSCT).

Thirty-seven patients discontinued study treatment for other reasons—17 of them during induction. Twenty-one patients discontinued due to progressive disease, 9 due to adverse events (AEs), 5 due to patient withdrawal, 1 due to unsatisfactory response, and 1 due to other reasons.

Twenty-five patients completed induction and went on to receive ixazomib maintenance. Five patients remain on study treatment.

Safety

Seventy-eight percent of patients had a grade 3 or higher AE, 46% had a serious AE, 57% had an AE leading to dose reduction, and 15% had an AE leading to discontinuation of any of the study drugs. There were 2 on-study deaths.

The most common grade 3 or higher AEs were neutropenia, thrombocytopenia, diarrhea, back pain, vomiting, nausea, peripheral neuropathy, and rashes/eruptions/exanthems.

Efficacy

The overall response rate was 88% for the entire cohort and 80% among patients who did not go on to receive HSCT.

The complete response (CR) rates were 23% and 32%, respectively. Thirty four percent and 32%, respectively, had a very good partial response (VGPR). And 30% and 17%, respectively, had a partial response (PR).

Thirty-two percent of patients who received maintenance (n=8) had an improvement in their response during the maintenance phase.  Two patients went from a VGPR to a stringent CR, 3 went from a VGPR to a CR, 2 went from a VGPR to a near CR, and 1 went from a PR to a VGPR.

Sixteen patients were evaluated for minimal residual disease (MRD). Of the patients with a stringent CR/CR, 89% (8/9) were MRD-negative.

The median progression-free survival was 35.4 months in the entire cohort and 29.4 months in patients who did not proceed to HSCT. The 4-year overall survival rate was 84% and 82%, respectively.

“Long-term follow-up, a median follow-up of 56 months, with the combination of ixazomib, lenalidomide, and dexamethasone demonstrates that this is an efficacious regimen for newly diagnosed myeloma patients, with excellent tolerability, and something that can be maintained for a long period of time,” Dr Kumar said. “These results form the basis for an ongoing phase 3 program.”

Diffuse large B-cell lymphoma

LUGANO, SWITZERLAND—The chimeric antigen receptor (CAR) T-cell therapy JCAR017 can produce “potent and durable” responses in patients with relapsed/refractory, aggressive diffuse large B-cell lymphoma (DLBCL), according to an investigator from the TRANSCEND NHL 001 trial.

In this phase 1 trial, JCAR017, given after lymphodepleting chemotherapy, produced an overall response rate (ORR) of 76% and a complete response (CR) rate of 52%.

At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.

Responses were seen even in poor-risk subgroups, noted study investigator Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.

“TRANSCEND NHL 001 is the first multicenter study of a CD19-directed CAR T-cell product with a fixed CD4 and CD8 composition to deliver potent and durable responses in high-risk subsets in DLBCL,” Dr Abramson said.

He presented data from the trial at the 2017 International Conference on Malignant Lymphoma (ICML) as abstract 128. The research was sponsored by Juno Therapeutics, the company developing JCAR017.

Patients

Dr Abramson presented data on 55 patients with relapsed/refractory non-Hodgkin lymphoma. Forty patients had DLBCL not otherwise specified, 14 had transformed DLBCL, and 1 had grade 3B follicular lymphoma. Fifteen patients had double- or triple-hit lymphoma.

The patients’ median age was 61 (range, 29-82), and 69% were male. Eighty-seven percent of patients (n=48) had an ECOG status of 0 to 1. Two patients had central nervous system involvement.

The patients had received a median of 3 prior lines of therapy (range, 1-11). Seventy-six percent of patients (n=42) were chemo-refractory, 7% (n=4) had received an allogeneic transplant, and 44% (n=24) had received an autologous transplant.

Treatment

Patients received 1 of 2 doses of JCAR017 after fludarabine/cyclophosphamide lymphodepletion.

Thirty patients received a single dose of JCAR017 at 5 x 10⁷ CAR cells (dose-level 1, single [DL1S]).

Six patients received 2 doses of 5 x 10⁷ CAR cells (dose-level 1, double [DL1D]).

Nineteen patients received a single dose of 1 x 10⁸ CAR cells (dose-level 2, single [DL2S]).

Safety

More than 90% of patients experienced a treatment-emergent adverse event (AE), and 60% had a treatment-related AE.

Treatment-emergent AEs occurring in more than 20% of patients included cytokine release syndrome (CRS), fatigue, nausea, constipation, decreased appetite, diarrhea, hypotension, neutropenia, anemia, and thrombocytopenia.

One patient had a grade 5 AE of diffuse alveolar damage that was thought to be related to fludarabine, cyclophosphamide, and JCAR017.

Another patient had a grade 5 AE of multiorgan failure that was considered unrelated to study treatment and due to disease progression.

The rate of grade 1/2 CRS was 33% (n=18), and the rate of grade 3/4 CRS was 2% (n=1). The rate of grade 1/2 neurotoxicity was 6% (n=3), and the rate of grade 3/4 neurotoxicity was 16% (n=9).

There were no deaths from CRS or neurotoxicity. The median time to onset of CRS was 5 days (range, 1-23), and the median time to onset of neurotoxicity was 11 days (range, 5-23).

“JCAR017 toxicities have, thus far, been relatively low and highly manageable at all dose levels tested, with a favorable safety profile that may enable outpatient administration,” Dr Abramson said.

Response

Fifty-four patients were evaluable for response. The ORR was 76%, and the CR rate was 52%. At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.

Dr Abramson noted that there was a dose-response relationship.

Overall, in the DL1S cohort, the ORR was 80%, and the CR rate was 53%. In the DL2S cohort, the ORR was 72%, and the CR rate was 50%. In the DL1D cohort, the ORR was 67%, and the CR rate was 50%.

At 3 months, in the DL1S cohort, the ORR was 46%, and the CR rate was 33%. In the DL2S cohort, the ORR was 64%, and the CR rate was 46%. In the DL1D cohort, the ORR and CR rate were both 50%.

Dr Abramson also noted that JCAR017 could produce a high response rate in poor-risk subgroups.

At 3 months, the ORR was 91% in patients who relapsed less than 12 months after transplant, 82% in patients with double- or triple-hit lymphoma, 48% in patients who had never achieved a CR, 47% in chemo-refractory patients, 31% in patients with primary refractory lymphoma, and 24% in patients with stable disease or progression after last chemotherapy.

Diffuse large B-cell lymphoma

LUGANO, SWITZERLAND—The chimeric antigen receptor (CAR) T-cell therapy JCAR017 can produce “potent and durable” responses in patients with relapsed/refractory, aggressive diffuse large B-cell lymphoma (DLBCL), according to an investigator from the TRANSCEND NHL 001 trial.

In this phase 1 trial, JCAR017, given after lymphodepleting chemotherapy, produced an overall response rate (ORR) of 76% and a complete response (CR) rate of 52%.

At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.

Responses were seen even in poor-risk subgroups, noted study investigator Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.

“TRANSCEND NHL 001 is the first multicenter study of a CD19-directed CAR T-cell product with a fixed CD4 and CD8 composition to deliver potent and durable responses in high-risk subsets in DLBCL,” Dr Abramson said.

He presented data from the trial at the 2017 International Conference on Malignant Lymphoma (ICML) as abstract 128. The research was sponsored by Juno Therapeutics, the company developing JCAR017.

Patients

Dr Abramson presented data on 55 patients with relapsed/refractory non-Hodgkin lymphoma. Forty patients had DLBCL not otherwise specified, 14 had transformed DLBCL, and 1 had grade 3B follicular lymphoma. Fifteen patients had double- or triple-hit lymphoma.

The patients’ median age was 61 (range, 29-82), and 69% were male. Eighty-seven percent of patients (n=48) had an ECOG status of 0 to 1. Two patients had central nervous system involvement.

The patients had received a median of 3 prior lines of therapy (range, 1-11). Seventy-six percent of patients (n=42) were chemo-refractory, 7% (n=4) had received an allogeneic transplant, and 44% (n=24) had received an autologous transplant.

Treatment

Patients received 1 of 2 doses of JCAR017 after fludarabine/cyclophosphamide lymphodepletion.

Thirty patients received a single dose of JCAR017 at 5 x 10⁷ CAR cells (dose-level 1, single [DL1S]).

Six patients received 2 doses of 5 x 10⁷ CAR cells (dose-level 1, double [DL1D]).

Nineteen patients received a single dose of 1 x 10⁸ CAR cells (dose-level 2, single [DL2S]).

Safety

More than 90% of patients experienced a treatment-emergent adverse event (AE), and 60% had a treatment-related AE.

Treatment-emergent AEs occurring in more than 20% of patients included cytokine release syndrome (CRS), fatigue, nausea, constipation, decreased appetite, diarrhea, hypotension, neutropenia, anemia, and thrombocytopenia.

One patient had a grade 5 AE of diffuse alveolar damage that was thought to be related to fludarabine, cyclophosphamide, and JCAR017.

Another patient had a grade 5 AE of multiorgan failure that was considered unrelated to study treatment and due to disease progression.

The rate of grade 1/2 CRS was 33% (n=18), and the rate of grade 3/4 CRS was 2% (n=1). The rate of grade 1/2 neurotoxicity was 6% (n=3), and the rate of grade 3/4 neurotoxicity was 16% (n=9).

There were no deaths from CRS or neurotoxicity. The median time to onset of CRS was 5 days (range, 1-23), and the median time to onset of neurotoxicity was 11 days (range, 5-23).

“JCAR017 toxicities have, thus far, been relatively low and highly manageable at all dose levels tested, with a favorable safety profile that may enable outpatient administration,” Dr Abramson said.

Response

Fifty-four patients were evaluable for response. The ORR was 76%, and the CR rate was 52%. At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.

Dr Abramson noted that there was a dose-response relationship.

Overall, in the DL1S cohort, the ORR was 80%, and the CR rate was 53%. In the DL2S cohort, the ORR was 72%, and the CR rate was 50%. In the DL1D cohort, the ORR was 67%, and the CR rate was 50%.

At 3 months, in the DL1S cohort, the ORR was 46%, and the CR rate was 33%. In the DL2S cohort, the ORR was 64%, and the CR rate was 46%. In the DL1D cohort, the ORR and CR rate were both 50%.

Dr Abramson also noted that JCAR017 could produce a high response rate in poor-risk subgroups.

At 3 months, the ORR was 91% in patients who relapsed less than 12 months after transplant, 82% in patients with double- or triple-hit lymphoma, 48% in patients who had never achieved a CR, 47% in chemo-refractory patients, 31% in patients with primary refractory lymphoma, and 24% in patients with stable disease or progression after last chemotherapy.

Diffuse large B-cell lymphoma

LUGANO, SWITZERLAND—The chimeric antigen receptor (CAR) T-cell therapy JCAR017 can produce “potent and durable” responses in patients with relapsed/refractory, aggressive diffuse large B-cell lymphoma (DLBCL), according to an investigator from the TRANSCEND NHL 001 trial.

In this phase 1 trial, JCAR017, given after lymphodepleting chemotherapy, produced an overall response rate (ORR) of 76% and a complete response (CR) rate of 52%.

At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.

Responses were seen even in poor-risk subgroups, noted study investigator Jeremy Abramson, MD, of Massachusetts General Hospital Cancer Center in Boston.

“TRANSCEND NHL 001 is the first multicenter study of a CD19-directed CAR T-cell product with a fixed CD4 and CD8 composition to deliver potent and durable responses in high-risk subsets in DLBCL,” Dr Abramson said.

He presented data from the trial at the 2017 International Conference on Malignant Lymphoma (ICML) as abstract 128. The research was sponsored by Juno Therapeutics, the company developing JCAR017.

Patients

Dr Abramson presented data on 55 patients with relapsed/refractory non-Hodgkin lymphoma. Forty patients had DLBCL not otherwise specified, 14 had transformed DLBCL, and 1 had grade 3B follicular lymphoma. Fifteen patients had double- or triple-hit lymphoma.

The patients’ median age was 61 (range, 29-82), and 69% were male. Eighty-seven percent of patients (n=48) had an ECOG status of 0 to 1. Two patients had central nervous system involvement.

The patients had received a median of 3 prior lines of therapy (range, 1-11). Seventy-six percent of patients (n=42) were chemo-refractory, 7% (n=4) had received an allogeneic transplant, and 44% (n=24) had received an autologous transplant.

Treatment

Patients received 1 of 2 doses of JCAR017 after fludarabine/cyclophosphamide lymphodepletion.

Thirty patients received a single dose of JCAR017 at 5 x 10⁷ CAR cells (dose-level 1, single [DL1S]).

Six patients received 2 doses of 5 x 10⁷ CAR cells (dose-level 1, double [DL1D]).

Nineteen patients received a single dose of 1 x 10⁸ CAR cells (dose-level 2, single [DL2S]).

Safety

More than 90% of patients experienced a treatment-emergent adverse event (AE), and 60% had a treatment-related AE.

Treatment-emergent AEs occurring in more than 20% of patients included cytokine release syndrome (CRS), fatigue, nausea, constipation, decreased appetite, diarrhea, hypotension, neutropenia, anemia, and thrombocytopenia.

One patient had a grade 5 AE of diffuse alveolar damage that was thought to be related to fludarabine, cyclophosphamide, and JCAR017.

Another patient had a grade 5 AE of multiorgan failure that was considered unrelated to study treatment and due to disease progression.

The rate of grade 1/2 CRS was 33% (n=18), and the rate of grade 3/4 CRS was 2% (n=1). The rate of grade 1/2 neurotoxicity was 6% (n=3), and the rate of grade 3/4 neurotoxicity was 16% (n=9).

There were no deaths from CRS or neurotoxicity. The median time to onset of CRS was 5 days (range, 1-23), and the median time to onset of neurotoxicity was 11 days (range, 5-23).

“JCAR017 toxicities have, thus far, been relatively low and highly manageable at all dose levels tested, with a favorable safety profile that may enable outpatient administration,” Dr Abramson said.

Response

Fifty-four patients were evaluable for response. The ORR was 76%, and the CR rate was 52%. At 3 months of follow-up, the ORR was 51%, and the CR rate was 39%.

Dr Abramson noted that there was a dose-response relationship.

Overall, in the DL1S cohort, the ORR was 80%, and the CR rate was 53%. In the DL2S cohort, the ORR was 72%, and the CR rate was 50%. In the DL1D cohort, the ORR was 67%, and the CR rate was 50%.

At 3 months, in the DL1S cohort, the ORR was 46%, and the CR rate was 33%. In the DL2S cohort, the ORR was 64%, and the CR rate was 46%. In the DL1D cohort, the ORR and CR rate were both 50%.

Dr Abramson also noted that JCAR017 could produce a high response rate in poor-risk subgroups.

At 3 months, the ORR was 91% in patients who relapsed less than 12 months after transplant, 82% in patients with double- or triple-hit lymphoma, 48% in patients who had never achieved a CR, 47% in chemo-refractory patients, 31% in patients with primary refractory lymphoma, and 24% in patients with stable disease or progression after last chemotherapy.

Photo by Chad McNeeley

MADRID—Updated results of a phase 1/2 study suggest the T-cell product BPX-501 lowers the risks associated with haploidentical hematopoietic stem cell transplant (haplo-HSCT).

In this ongoing study, researchers are testing BPX-501 in pediatric patients undergoing haplo-HSCT to treat a range of hematologic disorders.

Patients treated thus far have experienced rapid engraftment and early hospital discharge, a low rate of acute graft-versus-host disease (GHVD), no extensive chronic GVHD, and a low rate of transplant-related mortality at 180 days.

“The combination of haploidentical transplantation and BPX-501 infusion is an effective strategy for children in need of an allograft lacking a compatible donor,” said study investigator Mattia Algeri, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.

Dr Algeri presented these results during the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) as abstract S146.

The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.

About BPX-501

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haplo-HSCTs.

Patients

Dr Algeri and his colleagues have tested BPX-501 in 98 pediatric patients treated at centers in Europe and the US.

Fifty-nine patients had non-malignant conditions, including primary immune deficiency (n=26), thalassemia major (n=8), sickle cell disease (n=5), Diamond-Blackfan anemia (n=2), Swachman-Diamond syndrome (n=1), Fanconi anemia (n=9), hemophagocytic lymphohistiocytosis (n=6), aplastic anemia (n=1), and osteoporosis (n=1).

Thirty-nine patients had malignant conditions, including acute lymphoblastic leukemia (ALL, n=21), acute myeloid leukemia (AML, n=14), myelodysplastic syndromes (MDS, n=3), and non-Hodgkin lymphoma (NHL, n=1).

The patients received BPX-501 after an alpha/beta T-cell-depleted haplo-HSCT. All patients had at least 6 months of follow-up.

Overall results

Ninety-five percent of the patients engrafted (93/98), and the researchers said they observed rapid recovery of T cells, B cells, and immunoglobulins.

At 180 days, the incidence of transplant-related mortality was 5%, and there were no cases of post-transplant lymphoproliferative disorder.

The cumulative incidence of grade 2-4 acute GVHD was 14%. For patients with at least 1 year of follow-up, the cumulative incidence of chronic GVHD at 1 year was 3%.

Eleven patients received rimiducid—10 who had uncontrollable acute GVHD and 1 who developed late acute GVHD. In all of these patients, GVHD resolved and has not recurred.

There were no adverse events associated with BPX-501 or rimiducid.

European cohort

Dr Algeri presented more detailed data on the 61 patients treated at centers in Europe.

Fifteen of these patients had ALL, 10 had AML, 16 had primary immune deficiency, 7 had thalassemia major, 1 had sickle cell disease, 2 had Diamond-Blackfan anemia, 5 had Fanconi anemia, 4 had hemophagocytic lymphohistiocytosis, and 1 had osteoporosis.

Their median age was 4.8 (range, 0.25-17), and 56% were male. The patients received busulfan-based conditioning (41%), total body irradiation (36%), treosulfan-based conditioning (18%), and other conditioning (5%).

Ninety-five percent of the patients had a parent donor, and the other 5% had a sibling donor. The median donor age was 36 (range, 19-50).

The patients’ median time to neutrophil recovery was 15 days (range, 9-75), and their median time to platelet recovery was 10 days (range, 4-64). Their median time to discharge was 25 days (range, 14-122).

The cumulative incidence of acute grade 2-4 GVHD was 9.9%, and the cumulative incidence of acute grade 3-4 GVHD was 3.3%.

There were no cases of transplant-related mortality at 180 days and no cases of extensive chronic GVHD.

“These preliminary data compare favorably to previously published data on matched, unrelated donor transplantation,” Dr Algeri said. “And for this reason, an observational matched, unrelated donor study is being initiated to enable comparison of the safety and efficacy of haploidentical transplantation and BPX-501 infusion to the standard of care for patients without a matched sibling donor.”

Photo by Chad McNeeley

MADRID—Updated results of a phase 1/2 study suggest the T-cell product BPX-501 lowers the risks associated with haploidentical hematopoietic stem cell transplant (haplo-HSCT).

In this ongoing study, researchers are testing BPX-501 in pediatric patients undergoing haplo-HSCT to treat a range of hematologic disorders.

Patients treated thus far have experienced rapid engraftment and early hospital discharge, a low rate of acute graft-versus-host disease (GHVD), no extensive chronic GVHD, and a low rate of transplant-related mortality at 180 days.

“The combination of haploidentical transplantation and BPX-501 infusion is an effective strategy for children in need of an allograft lacking a compatible donor,” said study investigator Mattia Algeri, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.

Dr Algeri presented these results during the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) as abstract S146.

The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.

About BPX-501

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haplo-HSCTs.

Patients

Dr Algeri and his colleagues have tested BPX-501 in 98 pediatric patients treated at centers in Europe and the US.

Fifty-nine patients had non-malignant conditions, including primary immune deficiency (n=26), thalassemia major (n=8), sickle cell disease (n=5), Diamond-Blackfan anemia (n=2), Swachman-Diamond syndrome (n=1), Fanconi anemia (n=9), hemophagocytic lymphohistiocytosis (n=6), aplastic anemia (n=1), and osteoporosis (n=1).

Thirty-nine patients had malignant conditions, including acute lymphoblastic leukemia (ALL, n=21), acute myeloid leukemia (AML, n=14), myelodysplastic syndromes (MDS, n=3), and non-Hodgkin lymphoma (NHL, n=1).

The patients received BPX-501 after an alpha/beta T-cell-depleted haplo-HSCT. All patients had at least 6 months of follow-up.

Overall results

Ninety-five percent of the patients engrafted (93/98), and the researchers said they observed rapid recovery of T cells, B cells, and immunoglobulins.

At 180 days, the incidence of transplant-related mortality was 5%, and there were no cases of post-transplant lymphoproliferative disorder.

The cumulative incidence of grade 2-4 acute GVHD was 14%. For patients with at least 1 year of follow-up, the cumulative incidence of chronic GVHD at 1 year was 3%.

Eleven patients received rimiducid—10 who had uncontrollable acute GVHD and 1 who developed late acute GVHD. In all of these patients, GVHD resolved and has not recurred.

There were no adverse events associated with BPX-501 or rimiducid.

European cohort

Dr Algeri presented more detailed data on the 61 patients treated at centers in Europe.

Fifteen of these patients had ALL, 10 had AML, 16 had primary immune deficiency, 7 had thalassemia major, 1 had sickle cell disease, 2 had Diamond-Blackfan anemia, 5 had Fanconi anemia, 4 had hemophagocytic lymphohistiocytosis, and 1 had osteoporosis.

Their median age was 4.8 (range, 0.25-17), and 56% were male. The patients received busulfan-based conditioning (41%), total body irradiation (36%), treosulfan-based conditioning (18%), and other conditioning (5%).

Ninety-five percent of the patients had a parent donor, and the other 5% had a sibling donor. The median donor age was 36 (range, 19-50).

The patients’ median time to neutrophil recovery was 15 days (range, 9-75), and their median time to platelet recovery was 10 days (range, 4-64). Their median time to discharge was 25 days (range, 14-122).

The cumulative incidence of acute grade 2-4 GVHD was 9.9%, and the cumulative incidence of acute grade 3-4 GVHD was 3.3%.

There were no cases of transplant-related mortality at 180 days and no cases of extensive chronic GVHD.

“These preliminary data compare favorably to previously published data on matched, unrelated donor transplantation,” Dr Algeri said. “And for this reason, an observational matched, unrelated donor study is being initiated to enable comparison of the safety and efficacy of haploidentical transplantation and BPX-501 infusion to the standard of care for patients without a matched sibling donor.”

Photo by Chad McNeeley

MADRID—Updated results of a phase 1/2 study suggest the T-cell product BPX-501 lowers the risks associated with haploidentical hematopoietic stem cell transplant (haplo-HSCT).

In this ongoing study, researchers are testing BPX-501 in pediatric patients undergoing haplo-HSCT to treat a range of hematologic disorders.

Patients treated thus far have experienced rapid engraftment and early hospital discharge, a low rate of acute graft-versus-host disease (GHVD), no extensive chronic GVHD, and a low rate of transplant-related mortality at 180 days.

“The combination of haploidentical transplantation and BPX-501 infusion is an effective strategy for children in need of an allograft lacking a compatible donor,” said study investigator Mattia Algeri, MD, of Ospedale Pediatrico Bambino Gesù in Rome, Italy.

Dr Algeri presented these results during the Presidential Symposium at the 22nd Congress of the European Hematology Association (EHA) as abstract S146.

The research was sponsored by Bellicum Pharmaceuticals, Inc., the company developing BPX-501.

About BPX-501

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate the T cells in the event of toxicity.

Rimiducid is used to activate the CaspaCIDe safety switch, which consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway.

The goal of this therapy is to allow physicians to more safely perform haplo-HSCTs.

Patients

Dr Algeri and his colleagues have tested BPX-501 in 98 pediatric patients treated at centers in Europe and the US.

Fifty-nine patients had non-malignant conditions, including primary immune deficiency (n=26), thalassemia major (n=8), sickle cell disease (n=5), Diamond-Blackfan anemia (n=2), Swachman-Diamond syndrome (n=1), Fanconi anemia (n=9), hemophagocytic lymphohistiocytosis (n=6), aplastic anemia (n=1), and osteoporosis (n=1).

Thirty-nine patients had malignant conditions, including acute lymphoblastic leukemia (ALL, n=21), acute myeloid leukemia (AML, n=14), myelodysplastic syndromes (MDS, n=3), and non-Hodgkin lymphoma (NHL, n=1).

The patients received BPX-501 after an alpha/beta T-cell-depleted haplo-HSCT. All patients had at least 6 months of follow-up.

Overall results

Ninety-five percent of the patients engrafted (93/98), and the researchers said they observed rapid recovery of T cells, B cells, and immunoglobulins.

At 180 days, the incidence of transplant-related mortality was 5%, and there were no cases of post-transplant lymphoproliferative disorder.

The cumulative incidence of grade 2-4 acute GVHD was 14%. For patients with at least 1 year of follow-up, the cumulative incidence of chronic GVHD at 1 year was 3%.

Eleven patients received rimiducid—10 who had uncontrollable acute GVHD and 1 who developed late acute GVHD. In all of these patients, GVHD resolved and has not recurred.

There were no adverse events associated with BPX-501 or rimiducid.

European cohort

Dr Algeri presented more detailed data on the 61 patients treated at centers in Europe.

Fifteen of these patients had ALL, 10 had AML, 16 had primary immune deficiency, 7 had thalassemia major, 1 had sickle cell disease, 2 had Diamond-Blackfan anemia, 5 had Fanconi anemia, 4 had hemophagocytic lymphohistiocytosis, and 1 had osteoporosis.

Their median age was 4.8 (range, 0.25-17), and 56% were male. The patients received busulfan-based conditioning (41%), total body irradiation (36%), treosulfan-based conditioning (18%), and other conditioning (5%).

Ninety-five percent of the patients had a parent donor, and the other 5% had a sibling donor. The median donor age was 36 (range, 19-50).

The patients’ median time to neutrophil recovery was 15 days (range, 9-75), and their median time to platelet recovery was 10 days (range, 4-64). Their median time to discharge was 25 days (range, 14-122).

The cumulative incidence of acute grade 2-4 GVHD was 9.9%, and the cumulative incidence of acute grade 3-4 GVHD was 3.3%.

There were no cases of transplant-related mortality at 180 days and no cases of extensive chronic GVHD.

“These preliminary data compare favorably to previously published data on matched, unrelated donor transplantation,” Dr Algeri said. “And for this reason, an observational matched, unrelated donor study is being initiated to enable comparison of the safety and efficacy of haploidentical transplantation and BPX-501 infusion to the standard of care for patients without a matched sibling donor.”