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Two-drug combo deemed ‘very promising’ for PMBCL
SAN DIEGO—Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.
Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.
“It’s very promising . . . to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president and head of medical at Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.
Dr. Eid also noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.
These results were presented as a poster at the 2018 ASH Annual Meeting (abstract 1691).
Rationale
Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.
“The initial therapy works well in 70% to 80% of patients, but the patients who fail don’t have good options,” he said.
Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.
Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.
Patients and treatment
The interim analysis of this trial included 30 patients with relapsed/refractory PMCBL. Their median age at enrollment was 35.5 (range, 19 to 83), and 57% of patients were female.
Sixty percent of patients had refractory disease, 23% had relapsed disease, and 17% had both.
The median number of prior therapies was 2 (range, 1-5). Thirteen percent of patients had prior autologous stem cell transplant.
The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.
At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit (n=9), disease progression (n=7), AEs unrelated to treatment (n=2), patient request (n=1), and “other” reasons (n=1).
Safety
“There were no new safety signals,” Dr. Eid said. “The adverse events reflected the two agents’ profiles.”
The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).
Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).
The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.
The acute kidney injury was the only fatal AE considered treatment-related. There were three other deaths in the trial, but they were considered unrelated to treatment.
Response
The complete response rate was 27% (n=8), and the partial response rate was 43% (n=13), for an overall response rate of 70% (n=21).
“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.
Ten percent of patients (n=3) had stable disease, 13% (n=4) progressed, and investigators were unable to determine the status for 7% of patients (n=2).
The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.
Overall and progression-free survival data are not yet mature.
Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.
“The results are very, very promising,” Dr. Eid said.
This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics.
SAN DIEGO—Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.
Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.
“It’s very promising . . . to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president and head of medical at Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.
Dr. Eid also noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.
These results were presented as a poster at the 2018 ASH Annual Meeting (abstract 1691).
Rationale
Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.
“The initial therapy works well in 70% to 80% of patients, but the patients who fail don’t have good options,” he said.
Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.
Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.
Patients and treatment
The interim analysis of this trial included 30 patients with relapsed/refractory PMCBL. Their median age at enrollment was 35.5 (range, 19 to 83), and 57% of patients were female.
Sixty percent of patients had refractory disease, 23% had relapsed disease, and 17% had both.
The median number of prior therapies was 2 (range, 1-5). Thirteen percent of patients had prior autologous stem cell transplant.
The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.
At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit (n=9), disease progression (n=7), AEs unrelated to treatment (n=2), patient request (n=1), and “other” reasons (n=1).
Safety
“There were no new safety signals,” Dr. Eid said. “The adverse events reflected the two agents’ profiles.”
The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).
Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).
The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.
The acute kidney injury was the only fatal AE considered treatment-related. There were three other deaths in the trial, but they were considered unrelated to treatment.
Response
The complete response rate was 27% (n=8), and the partial response rate was 43% (n=13), for an overall response rate of 70% (n=21).
“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.
Ten percent of patients (n=3) had stable disease, 13% (n=4) progressed, and investigators were unable to determine the status for 7% of patients (n=2).
The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.
Overall and progression-free survival data are not yet mature.
Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.
“The results are very, very promising,” Dr. Eid said.
This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics.
SAN DIEGO—Nivolumab plus brentuximab vedotin may be a new treatment option for patients with relapsed/refractory primary mediastinal large B-cell lymphoma (PMBCL), according to investigators from the CheckMate 436 trial.
Interim results from this phase 1/2 trial revealed an overall response rate of 70%, including a complete response rate of 27%.
“It’s very promising . . . to see this level of activity in this advanced, relapsed/refractory population,” said Joseph E. Eid, MD, senior vice president and head of medical at Bristol-Myers Squibb, which is sponsoring CheckMate 436 in collaboration with Seattle Genetics.
Dr. Eid also noted that adverse events (AEs) observed with this regimen were consistent with the safety profiles of nivolumab and brentuximab vedotin alone.
These results were presented as a poster at the 2018 ASH Annual Meeting (abstract 1691).
Rationale
Dr. Eid noted that patients with relapsed or refractory PMBCL have limited treatment options.
“The initial therapy works well in 70% to 80% of patients, but the patients who fail don’t have good options,” he said.
Prior research has shown that PMBCL is often characterized by overexpression of the PD-1 ligands PD-L1 and PD-L2, and most PMBCL expresses CD30.
Dr. Eid said CheckMate 436 (NCT02581631) was designed to “take advantage” of these characteristics by employing the anti-PD-1 checkpoint inhibitor nivolumab and the anti-CD30 antibody-drug conjugate brentuximab vedotin.
Patients and treatment
The interim analysis of this trial included 30 patients with relapsed/refractory PMCBL. Their median age at enrollment was 35.5 (range, 19 to 83), and 57% of patients were female.
Sixty percent of patients had refractory disease, 23% had relapsed disease, and 17% had both.
The median number of prior therapies was 2 (range, 1-5). Thirteen percent of patients had prior autologous stem cell transplant.
The patients received nivolumab at 240 mg and brentuximab vedotin at 1.8 mg/kg every 3 weeks until progression or unacceptable toxicity.
At a median follow-up of 6.1 months, 10 patients were still on treatment. Reasons for discontinuation included maximum clinical benefit (n=9), disease progression (n=7), AEs unrelated to treatment (n=2), patient request (n=1), and “other” reasons (n=1).
Safety
“There were no new safety signals,” Dr. Eid said. “The adverse events reflected the two agents’ profiles.”
The rate of treatment-related AEs was 83%. The most common of these were neutropenia (27%), peripheral neuropathy (20%), hyperthyroidism (13%), rash (10%), and thrombocytopenia (10%).
Grade 3-4 treatment-related AEs included neutropenia (27%), thrombocytopenia (7%), decreased neutrophil count (7%), hypersensitivity (3%), diarrhea (3%), and maculopapular rash (3%).
The rate of serious treatment-related AEs was 10%. This included grade 3-4 diarrhea and maculopapular rash and grade 5 acute kidney injury.
The acute kidney injury was the only fatal AE considered treatment-related. There were three other deaths in the trial, but they were considered unrelated to treatment.
Response
The complete response rate was 27% (n=8), and the partial response rate was 43% (n=13), for an overall response rate of 70% (n=21).
“The early indication is that 70% response is a pretty good outcome in a relapsed/refractory population that, otherwise, their outcome is pretty dismal,” Dr. Eid said.
Ten percent of patients (n=3) had stable disease, 13% (n=4) progressed, and investigators were unable to determine the status for 7% of patients (n=2).
The median time to response was 1.3 months, and the median time to complete response was 3.0 months. The median duration of response and complete response were not reached.
Overall and progression-free survival data are not yet mature.
Still, the investigators concluded that nivolumab and brentuximab vedotin “may provide a new treatment option” for patients with relapsed/refractory PMBCL.
“The results are very, very promising,” Dr. Eid said.
This trial is supported by Bristol-Myers Squibb in collaboration with Seattle Genetics.
Data support apixaban for cancer-associated VTE, doc says
SAN DIEGO—Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the ADAM VTE trial.
Patients who received apixaban in this trial had similar rates of major bleeding and clinically relevant non-major bleeding as patients who received dalteparin.
However, the rate of VTE recurrence was significantly lower with apixaban than with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane, MD, of the Mayo Clinic in Rochester, Minnesota.
Dr. McBane presented these results at the 2018 ASH Annual Meeting (abstract 421*).
ADAM VTE (NCT02585713) included 300 adults (age 18 and older) with active cancer and acute VTE who were randomized to receive apixaban (n=150) or dalteparin (n=150).
The dose and schedule for oral apixaban was 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month, followed by 150 IU/kg daily for 6 months.
One hundred and forty-five patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 in both arms, and roughly half of patients in both arms were female.
Nine percent of patients in the apixaban arm and 11% in the dalteparin arm had hematologic malignancies. Other cancers included colorectal, lung, pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Sixty-five percent of patients in the apixaban arm and 66% in the dalteparin arm had distant metastasis. Seventy-four percent of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE)—55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT)—48% and 47%, respectively
- PE only—44% and 39%, respectively
- PE with DVT—12% in both arms
- DVT only—37% and 35%, respectively
- Lower extremity DVT—31% and 34%, respectively
- Upper extremity DVT—17% and 14%, respectively
- Cerebral venous thrombosis (VT)—1% and 0%, respectively
- Splanchnic VT—8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P=0.14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P=0.88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P=0.03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n=4) or arm (n=2) VTE, PE (n=1), or splanchnic VT (n=2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio=1.40; P=0.3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to:
- Be concerned about excessive bruising
- Find anticoagulant treatment a burden or difficult to carry out
- Say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were also less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence.
Still, the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group—15% and 4%, respectively (P=0.0012).
“Apixaban was well tolerated with superior patient safety satisfaction as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
*Data in the presentation differ from the abstract.
SAN DIEGO—Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the ADAM VTE trial.
Patients who received apixaban in this trial had similar rates of major bleeding and clinically relevant non-major bleeding as patients who received dalteparin.
However, the rate of VTE recurrence was significantly lower with apixaban than with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane, MD, of the Mayo Clinic in Rochester, Minnesota.
Dr. McBane presented these results at the 2018 ASH Annual Meeting (abstract 421*).
ADAM VTE (NCT02585713) included 300 adults (age 18 and older) with active cancer and acute VTE who were randomized to receive apixaban (n=150) or dalteparin (n=150).
The dose and schedule for oral apixaban was 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month, followed by 150 IU/kg daily for 6 months.
One hundred and forty-five patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 in both arms, and roughly half of patients in both arms were female.
Nine percent of patients in the apixaban arm and 11% in the dalteparin arm had hematologic malignancies. Other cancers included colorectal, lung, pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Sixty-five percent of patients in the apixaban arm and 66% in the dalteparin arm had distant metastasis. Seventy-four percent of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE)—55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT)—48% and 47%, respectively
- PE only—44% and 39%, respectively
- PE with DVT—12% in both arms
- DVT only—37% and 35%, respectively
- Lower extremity DVT—31% and 34%, respectively
- Upper extremity DVT—17% and 14%, respectively
- Cerebral venous thrombosis (VT)—1% and 0%, respectively
- Splanchnic VT—8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P=0.14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P=0.88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P=0.03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n=4) or arm (n=2) VTE, PE (n=1), or splanchnic VT (n=2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio=1.40; P=0.3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to:
- Be concerned about excessive bruising
- Find anticoagulant treatment a burden or difficult to carry out
- Say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were also less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence.
Still, the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group—15% and 4%, respectively (P=0.0012).
“Apixaban was well tolerated with superior patient safety satisfaction as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
*Data in the presentation differ from the abstract.
SAN DIEGO—Apixaban is as safe as, and more effective than, dalteparin for patients with cancer-associated venous thromboembolism (VTE), according to the ADAM VTE trial.
Patients who received apixaban in this trial had similar rates of major bleeding and clinically relevant non-major bleeding as patients who received dalteparin.
However, the rate of VTE recurrence was significantly lower with apixaban than with dalteparin.
“[A]pixaban was associated with very low bleeding rates and venous thrombosis recurrence rates compared to dalteparin,” said Robert D. McBane, MD, of the Mayo Clinic in Rochester, Minnesota.
Dr. McBane presented these results at the 2018 ASH Annual Meeting (abstract 421*).
ADAM VTE (NCT02585713) included 300 adults (age 18 and older) with active cancer and acute VTE who were randomized to receive apixaban (n=150) or dalteparin (n=150).
The dose and schedule for oral apixaban was 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months. Dalteparin was given subcutaneously at 200 IU/kg per day for 1 month, followed by 150 IU/kg daily for 6 months.
One hundred and forty-five patients in the apixaban arm and 142 in the dalteparin arm ultimately received their assigned treatment.
Every month, patients completed an anticoagulation satisfaction survey and bruise survey (a modification of the Duke Anticoagulation Satisfaction Scale). They also underwent lab testing (complete blood count, liver and renal function testing) and were assessed for outcomes, medication reconciliation, drug compliance, and ECOG status on a monthly basis.
Patient characteristics
Baseline characteristics were similar between the treatment arms. The mean age was 64 in both arms, and roughly half of patients in both arms were female.
Nine percent of patients in the apixaban arm and 11% in the dalteparin arm had hematologic malignancies. Other cancers included colorectal, lung, pancreatic/hepatobiliary, gynecologic, breast, genitourinary, upper gastrointestinal, and brain cancers.
Sixty-five percent of patients in the apixaban arm and 66% in the dalteparin arm had distant metastasis. Seventy-four percent of patients in both arms were receiving chemotherapy while on study.
Patients had the following qualifying thrombotic events:
- Any pulmonary embolism (PE)—55% of patients in the apixaban arm and 51% in the dalteparin arm
- Any deep vein thrombosis (DVT)—48% and 47%, respectively
- PE only—44% and 39%, respectively
- PE with DVT—12% in both arms
- DVT only—37% and 35%, respectively
- Lower extremity DVT—31% and 34%, respectively
- Upper extremity DVT—17% and 14%, respectively
- Cerebral venous thrombosis (VT)—1% and 0%, respectively
- Splanchnic VT—8% and 18%, respectively.
Bleeding, thrombosis, and death
The study’s primary endpoint was major bleeding, which did not occur in any of the apixaban-treated patients. However, major bleeding did occur in two (1.4%) patients in the dalteparin arm (P=0.14).
A secondary endpoint was major bleeding plus clinically relevant nonmajor bleeding. This occurred in nine (6.2%) patients in the apixaban arm and nine (6.3%) in the dalteparin arm (P=0.88).
The researchers also assessed VTE recurrence. One patient in the apixaban arm (0.7%) and nine in the dalteparin arm (6.3%) had VTE recurrence (P=0.03).
The patient in the apixaban arm experienced cerebral VT, and the patients with recurrence in the dalteparin arm had leg (n=4) or arm (n=2) VTE, PE (n=1), or splanchnic VT (n=2).
One patient in each arm (0.7%) had arterial thrombosis.
There was no significant difference in cumulative mortality between the treatment arms (hazard ratio=1.40; P=0.3078).
Satisfaction and discontinuation
Overall, apixaban fared better than dalteparin in the monthly patient satisfaction surveys. At various time points, apixaban-treated patients were significantly less likely to:
- Be concerned about excessive bruising
- Find anticoagulant treatment a burden or difficult to carry out
- Say anticoagulant treatment added stress to their lives, negatively impacted their quality of life, or caused them “a great deal” of worry, irritation, or frustration.
However, apixaban-treated patients were also less likely than dalteparin recipients to have confidence that their drug protected them from VTE recurrence.
Still, the apixaban recipients were more likely than the dalteparin group to report overall satisfaction with their treatment.
In addition, premature treatment discontinuation was more common in the dalteparin group than in the apixaban group—15% and 4%, respectively (P=0.0012).
“Apixaban was well tolerated with superior patient safety satisfaction as well as significantly fewer study drug discontinuations compared to dalteparin,” Dr. McBane said. “I believe that these data support the use of apixaban for the acute treatment of cancer-associated venous thromboembolism.”
This study was funded by BMS/Pfizer Alliance. Dr. McBane declared no other conflicts of interest.
*Data in the presentation differ from the abstract.
Regimen provides survival benefit in PTCL
SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.
Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.
Patients and treatment
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).
Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.
Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).
Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.
Efficacy
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).
Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.
Safety
BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:
- Nausea (46% and 38%)
- Peripheral sensory neuropathy (45% and 41%)
- Neutropenia (38% for both)
- Diarrhea (38% and 20%)
- Constipation (29% and 30%)
- Alopecia (26% and 25%)
- Pyrexia (26% and 19%)
- Vomiting (26% and 17%)
- Fatigue (24% and 20%)
- Anemia (21% and 16%).
This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.
SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.
Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.
Patients and treatment
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).
Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.
Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).
Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.
Efficacy
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).
Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.
Safety
BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:
- Nausea (46% and 38%)
- Peripheral sensory neuropathy (45% and 41%)
- Neutropenia (38% for both)
- Diarrhea (38% and 20%)
- Constipation (29% and 30%)
- Alopecia (26% and 25%)
- Pyrexia (26% and 19%)
- Vomiting (26% and 17%)
- Fatigue (24% and 20%)
- Anemia (21% and 16%).
This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.
SAN DIEGO—A newly approved treatment regimen provides a survival benefit over standard therapy for patients with CD30-positive peripheral T-cell lymphomas (PTCLs), according to a presentation at the 2018 ASH Annual Meeting.
In the ECHELON-2 trial, patients who received brentuximab vedotin (BV) plus cyclophosphamide, doxorubicin, and prednisone (CHP) had superior progression-free survival (PFS) and overall survival (OS) compared to patients who received standard treatment with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP).
These results supported the recent U.S. approval of BV in combination with CHP for adults with previously untreated, systemic anaplastic large-cell lymphoma or other CD30-expressing PTCLs, including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified.
“ECHELON-2 is the first prospective trial in peripheral T-cell lymphoma to show an overall survival benefit over CHOP,” said Steven M. Horwitz, MD, of Memorial Sloan Kettering Cancer Center in Basking Ridge, New Jersey.
Dr. Horwitz presented results from this trial at ASH as abstract 997. Results were simultaneously published in The Lancet.
Patients and treatment
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive (n=98) or -negative (n=218) systemic anaplastic large-cell lymphoma, PTCL not otherwise specified (n=72), angioimmunoblastic T-cell lymphoma (n=54), enteropathy-associated T-cell lymphoma (n=7), and adult T-cell leukemia/lymphoma (n=3).
Patients were randomized to receive BV-CHP plus placebo (n=226) or CHOP plus placebo (n=226) every 3 weeks for six to eight cycles.
At baseline, the median age was 58 in both the BV-CHP arm (range, 18-85) and the CHOP arm (range, 18-83). The majority of patients were male—59% in the BV-CHP arm and 67% in the CHOP arm—and most patients had stage III/IV disease—81% and 80%, respectively.
Eighty-nine percent of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
Twenty-seven percent of patients in the BV-CHP arm and 19% in the CHOP arm received consolidation consisting of radiotherapy (6% and 3%, respectively) and/or stem cell transplant (22% and 17%).
Twenty-six percent of patients in the BV-CHP arm and 42% in the CHOP arm received systemic therapy for residual or progressive disease, and 4% of patients in each arm received palliative radiation.
Efficacy
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P=0.0032). The complete response rates were 68% and 56%, respectively (P=0.0066).
At a median follow-up of 36.2 months, the median PFS was 48.2 months in the BV-CHP arm and 20.8 months in the CHOP arm. The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio=0.71, P=0.011).
At a median follow-up of 42.1 months, the median OS was not reached in either treatment arm. The rate of death was 23% in the BV-CHP arm and 32% in the CHOP arm (hazard ratio=0.66, P=0.0244).
Dr. Horwitz noted that this study was not powered to determine differences in OS or PFS according to PTCL subtypes.
Safety
BV-CHP had a comparable safety profile to CHOP, Dr. Horwitz said.
The rate of adverse events (AEs) was 99% in the BV-CHP arm and 98% in the CHOP arm. Grade 3 or higher AEs occurred in 66% and 65% of patients, respectively. Serious AEs occurred in 39% and 38%, respectively.
Three percent of patients in the BV-CHP arm and 4% of those in the CHOP arm had fatal AEs.
The most common AEs of any grade occurring in at least 20% of patients (in the BV-CHP and CHOP arms, respectively) were:
- Nausea (46% and 38%)
- Peripheral sensory neuropathy (45% and 41%)
- Neutropenia (38% for both)
- Diarrhea (38% and 20%)
- Constipation (29% and 30%)
- Alopecia (26% and 25%)
- Pyrexia (26% and 19%)
- Vomiting (26% and 17%)
- Fatigue (24% and 20%)
- Anemia (21% and 16%).
This research was funded by Seattle Genetics Inc. and Millennium Pharmaceuticals Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited.
Dr. Horwitz disclosed relationships with Seattle Genetics, Aileron Therapeutics, Innate Pharma, Millennium/Takeda, Forty Seven, Corvus, Mundipharma, ADC Therapeutics, Trillium, Celgene, Portola, Infinity/Verastem, Spectrum, and Kyowa-Hakka-Kirin.
FDA approves venetoclax for AML
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to venetoclax (Venclexta®) for use in acute myeloid leukemia (AML).
The BCL-2 inhibitor is now approved for use in combination with azacitidine, decitabine, or low-dose cytarabine to treat adults with newly diagnosed AML who are age 75 and older or who are ineligible for intensive chemotherapy.
The FDA grants accelerated approval based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit.
Therefore, continued approval of venetoclax in AML may be contingent upon verification of clinical benefit in confirmatory trials.
The approval is based on data from two studies—the phase 1 b M14-358 trial (NCT02203773) and the phase 1/2 M14-387 trial (NCT02287233).
M14-358 trial
In M14-358, newly diagnosed AML patients received venetoclax in combination with azacitidine (n=84) or decitabine (n=31). There were 67 patients in the azacitidine arm and 13 in the decitabine arm who were 75 or older or were ineligible for intensive induction chemotherapy.
Patients received venetoclax via a daily ramp-up to a final dose of 400 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.
They received azacitidine at 75 mg/m2 on days 1-7 of each 28-day cycle or decitabine at 20 mg/m2 on days 1-5 of each cycle. Patients continued treatment until disease progression or unacceptable toxicity.
The median follow-up was 7.9 months for the azacitidine arm and 11 months for the decitabine arm.
The complete response (CR) rate was 37% (25/67) in the azacitidine arm and 54% (7/13) in the decitabine arm. The rates of CR with partial hematologic recovery were 24% (16/67) and 7.7% (1/13), respectively.
The most common adverse events (AEs)—occurring in at least 30% of patients in both arms—were nausea, diarrhea, constipation, neutropenia, thrombocytopenia, hemorrhage, peripheral edema, vomiting, fatigue, febrile neutropenia, rash, and anemia.
The incidence of serious AEs was 75% overall. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, pneumonia (excluding fungal), sepsis (excluding fungal), respiratory failure, and multiple organ dysfunction syndrome.
The incidence of fatal AEs was 1.5% within 30 days of treatment initiation.
M14-387 trial
The M14-387 trial included 82 AML patients who received venetoclax plus low-dose cytarabine. Patients were newly diagnosed with AML, but some had previous exposure to a hypomethylating agent for an antecedent hematologic disorder.
There were 61 patients who were 75 or older or were ineligible for intensive induction chemotherapy.
Patients received venetoclax via daily ramp-up to a final dose of 600 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.
Cytarabine was given at 20 mg/m2 on days 1-10 of each 28-day cycle. Patients continued to receive treatment until disease progression or unacceptable toxicity.
At a median follow-up of 6.5 months, the CR rate was 21% (13/61), and the rate of CR with partial hematologic recovery was 21% (13/61).
The most common AEs (occurring in at least 30% of patients) were nausea, thrombocytopenia, hemorrhage, febrile neutropenia, neutropenia, diarrhea, fatigue, constipation, and dyspnea.
The incidence of serious AEs was 95%. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, sepsis (excluding fungal), hemorrhage, pneumonia (excluding fungal), and device-related infection.
The incidence of fatal AEs was 4.9% within 30 days of treatment initiation.
Additional details from the M14-358 and M14-387 trials are available in the prescribing information for venetoclax.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie elsewhere.
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to venetoclax (Venclexta®) for use in acute myeloid leukemia (AML).
The BCL-2 inhibitor is now approved for use in combination with azacitidine, decitabine, or low-dose cytarabine to treat adults with newly diagnosed AML who are age 75 and older or who are ineligible for intensive chemotherapy.
The FDA grants accelerated approval based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit.
Therefore, continued approval of venetoclax in AML may be contingent upon verification of clinical benefit in confirmatory trials.
The approval is based on data from two studies—the phase 1 b M14-358 trial (NCT02203773) and the phase 1/2 M14-387 trial (NCT02287233).
M14-358 trial
In M14-358, newly diagnosed AML patients received venetoclax in combination with azacitidine (n=84) or decitabine (n=31). There were 67 patients in the azacitidine arm and 13 in the decitabine arm who were 75 or older or were ineligible for intensive induction chemotherapy.
Patients received venetoclax via a daily ramp-up to a final dose of 400 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.
They received azacitidine at 75 mg/m2 on days 1-7 of each 28-day cycle or decitabine at 20 mg/m2 on days 1-5 of each cycle. Patients continued treatment until disease progression or unacceptable toxicity.
The median follow-up was 7.9 months for the azacitidine arm and 11 months for the decitabine arm.
The complete response (CR) rate was 37% (25/67) in the azacitidine arm and 54% (7/13) in the decitabine arm. The rates of CR with partial hematologic recovery were 24% (16/67) and 7.7% (1/13), respectively.
The most common adverse events (AEs)—occurring in at least 30% of patients in both arms—were nausea, diarrhea, constipation, neutropenia, thrombocytopenia, hemorrhage, peripheral edema, vomiting, fatigue, febrile neutropenia, rash, and anemia.
The incidence of serious AEs was 75% overall. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, pneumonia (excluding fungal), sepsis (excluding fungal), respiratory failure, and multiple organ dysfunction syndrome.
The incidence of fatal AEs was 1.5% within 30 days of treatment initiation.
M14-387 trial
The M14-387 trial included 82 AML patients who received venetoclax plus low-dose cytarabine. Patients were newly diagnosed with AML, but some had previous exposure to a hypomethylating agent for an antecedent hematologic disorder.
There were 61 patients who were 75 or older or were ineligible for intensive induction chemotherapy.
Patients received venetoclax via daily ramp-up to a final dose of 600 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.
Cytarabine was given at 20 mg/m2 on days 1-10 of each 28-day cycle. Patients continued to receive treatment until disease progression or unacceptable toxicity.
At a median follow-up of 6.5 months, the CR rate was 21% (13/61), and the rate of CR with partial hematologic recovery was 21% (13/61).
The most common AEs (occurring in at least 30% of patients) were nausea, thrombocytopenia, hemorrhage, febrile neutropenia, neutropenia, diarrhea, fatigue, constipation, and dyspnea.
The incidence of serious AEs was 95%. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, sepsis (excluding fungal), hemorrhage, pneumonia (excluding fungal), and device-related infection.
The incidence of fatal AEs was 4.9% within 30 days of treatment initiation.
Additional details from the M14-358 and M14-387 trials are available in the prescribing information for venetoclax.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie elsewhere.
The U.S. Food and Drug Administration (FDA) has granted accelerated approval to venetoclax (Venclexta®) for use in acute myeloid leukemia (AML).
The BCL-2 inhibitor is now approved for use in combination with azacitidine, decitabine, or low-dose cytarabine to treat adults with newly diagnosed AML who are age 75 and older or who are ineligible for intensive chemotherapy.
The FDA grants accelerated approval based on a surrogate or intermediate endpoint that is reasonably likely to predict clinical benefit.
Therefore, continued approval of venetoclax in AML may be contingent upon verification of clinical benefit in confirmatory trials.
The approval is based on data from two studies—the phase 1 b M14-358 trial (NCT02203773) and the phase 1/2 M14-387 trial (NCT02287233).
M14-358 trial
In M14-358, newly diagnosed AML patients received venetoclax in combination with azacitidine (n=84) or decitabine (n=31). There were 67 patients in the azacitidine arm and 13 in the decitabine arm who were 75 or older or were ineligible for intensive induction chemotherapy.
Patients received venetoclax via a daily ramp-up to a final dose of 400 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.
They received azacitidine at 75 mg/m2 on days 1-7 of each 28-day cycle or decitabine at 20 mg/m2 on days 1-5 of each cycle. Patients continued treatment until disease progression or unacceptable toxicity.
The median follow-up was 7.9 months for the azacitidine arm and 11 months for the decitabine arm.
The complete response (CR) rate was 37% (25/67) in the azacitidine arm and 54% (7/13) in the decitabine arm. The rates of CR with partial hematologic recovery were 24% (16/67) and 7.7% (1/13), respectively.
The most common adverse events (AEs)—occurring in at least 30% of patients in both arms—were nausea, diarrhea, constipation, neutropenia, thrombocytopenia, hemorrhage, peripheral edema, vomiting, fatigue, febrile neutropenia, rash, and anemia.
The incidence of serious AEs was 75% overall. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, pneumonia (excluding fungal), sepsis (excluding fungal), respiratory failure, and multiple organ dysfunction syndrome.
The incidence of fatal AEs was 1.5% within 30 days of treatment initiation.
M14-387 trial
The M14-387 trial included 82 AML patients who received venetoclax plus low-dose cytarabine. Patients were newly diagnosed with AML, but some had previous exposure to a hypomethylating agent for an antecedent hematologic disorder.
There were 61 patients who were 75 or older or were ineligible for intensive induction chemotherapy.
Patients received venetoclax via daily ramp-up to a final dose of 600 mg once daily. They received prophylaxis for tumor lysis syndrome and were hospitalized for monitoring during the ramp-up.
Cytarabine was given at 20 mg/m2 on days 1-10 of each 28-day cycle. Patients continued to receive treatment until disease progression or unacceptable toxicity.
At a median follow-up of 6.5 months, the CR rate was 21% (13/61), and the rate of CR with partial hematologic recovery was 21% (13/61).
The most common AEs (occurring in at least 30% of patients) were nausea, thrombocytopenia, hemorrhage, febrile neutropenia, neutropenia, diarrhea, fatigue, constipation, and dyspnea.
The incidence of serious AEs was 95%. The most frequent serious AEs (occurring in at least 5% of patients) were febrile neutropenia, sepsis (excluding fungal), hemorrhage, pneumonia (excluding fungal), and device-related infection.
The incidence of fatal AEs was 4.9% within 30 days of treatment initiation.
Additional details from the M14-358 and M14-387 trials are available in the prescribing information for venetoclax.
Venetoclax is being developed by AbbVie and Roche. It is jointly commercialized by AbbVie and Genentech, a member of the Roche Group, in the United States and by AbbVie elsewhere.
FDA approves glasdegib for AML
The U.S. Food and Drug Administration (FDA) has approved the hedgehog pathway inhibitor glasdegib (Daurismo™) to treat certain patients with acute myeloid leukemia (AML).
Glasdegib is approved for use in combination with low-dose cytarabine (LDAC) to treat adults with newly diagnosed AML who are age 75 and older or who are ineligible for intensive chemotherapy.
Glasdegib was approved under priority review and also received orphan drug designation from the FDA.
The prescribing information for glasdegib includes a boxed warning detailing the risk of embryo-fetal death or severe birth defects associated with the drug.
The FDA’s approval of glasdegib is based on results from the phase 2 BRIGHT AML 1003 trial (NCT01546038).
This trial included 111 adults with newly diagnosed AML and 14 patients with other conditions.
The patients were randomized to receive glasdegib (at 100 mg daily) in combination with LDAC (n=84) or LDAC alone (n=41).
The complete response rate among the AML patients was 18.2% (14/77) in the glasdegib arm and 2.6% (1/38) in the LDAC arm.
The median overall survival was 8.3 months in the glasdegib arm and 4.3 months in the LDAC arm (hazard ratio=0.46; P=0.0002).
The most common adverse events (AEs) in the first 90 days of treatment—occurring in at least 30% of patients in either arm (glasdegib-LDAC and LDAC alone, respectively)—were:
- Anemia (43% and 42%)
- Fatigue (36% and 32%)
- Hemorrhage (36% and 42%)
- Febrile neutropenia (31% and 22%)
- Musculoskeletal pain (30% and 17%)
- Edema (30% and 20%)
- Thrombocytopenia (30% and 27%).
The incidence of serious AEs was 79% in the glasdegib arm. The most common serious AEs occurring in at least 5% of patients in this arm were febrile neutropenia (29%), pneumonia (23%), hemorrhage (12%), anemia (7%), and sepsis (7%).
Additional data from this trial are included in the prescribing information for glasdegib. Glasdegib is a product of Pfizer.
The U.S. Food and Drug Administration (FDA) has approved the hedgehog pathway inhibitor glasdegib (Daurismo™) to treat certain patients with acute myeloid leukemia (AML).
Glasdegib is approved for use in combination with low-dose cytarabine (LDAC) to treat adults with newly diagnosed AML who are age 75 and older or who are ineligible for intensive chemotherapy.
Glasdegib was approved under priority review and also received orphan drug designation from the FDA.
The prescribing information for glasdegib includes a boxed warning detailing the risk of embryo-fetal death or severe birth defects associated with the drug.
The FDA’s approval of glasdegib is based on results from the phase 2 BRIGHT AML 1003 trial (NCT01546038).
This trial included 111 adults with newly diagnosed AML and 14 patients with other conditions.
The patients were randomized to receive glasdegib (at 100 mg daily) in combination with LDAC (n=84) or LDAC alone (n=41).
The complete response rate among the AML patients was 18.2% (14/77) in the glasdegib arm and 2.6% (1/38) in the LDAC arm.
The median overall survival was 8.3 months in the glasdegib arm and 4.3 months in the LDAC arm (hazard ratio=0.46; P=0.0002).
The most common adverse events (AEs) in the first 90 days of treatment—occurring in at least 30% of patients in either arm (glasdegib-LDAC and LDAC alone, respectively)—were:
- Anemia (43% and 42%)
- Fatigue (36% and 32%)
- Hemorrhage (36% and 42%)
- Febrile neutropenia (31% and 22%)
- Musculoskeletal pain (30% and 17%)
- Edema (30% and 20%)
- Thrombocytopenia (30% and 27%).
The incidence of serious AEs was 79% in the glasdegib arm. The most common serious AEs occurring in at least 5% of patients in this arm were febrile neutropenia (29%), pneumonia (23%), hemorrhage (12%), anemia (7%), and sepsis (7%).
Additional data from this trial are included in the prescribing information for glasdegib. Glasdegib is a product of Pfizer.
The U.S. Food and Drug Administration (FDA) has approved the hedgehog pathway inhibitor glasdegib (Daurismo™) to treat certain patients with acute myeloid leukemia (AML).
Glasdegib is approved for use in combination with low-dose cytarabine (LDAC) to treat adults with newly diagnosed AML who are age 75 and older or who are ineligible for intensive chemotherapy.
Glasdegib was approved under priority review and also received orphan drug designation from the FDA.
The prescribing information for glasdegib includes a boxed warning detailing the risk of embryo-fetal death or severe birth defects associated with the drug.
The FDA’s approval of glasdegib is based on results from the phase 2 BRIGHT AML 1003 trial (NCT01546038).
This trial included 111 adults with newly diagnosed AML and 14 patients with other conditions.
The patients were randomized to receive glasdegib (at 100 mg daily) in combination with LDAC (n=84) or LDAC alone (n=41).
The complete response rate among the AML patients was 18.2% (14/77) in the glasdegib arm and 2.6% (1/38) in the LDAC arm.
The median overall survival was 8.3 months in the glasdegib arm and 4.3 months in the LDAC arm (hazard ratio=0.46; P=0.0002).
The most common adverse events (AEs) in the first 90 days of treatment—occurring in at least 30% of patients in either arm (glasdegib-LDAC and LDAC alone, respectively)—were:
- Anemia (43% and 42%)
- Fatigue (36% and 32%)
- Hemorrhage (36% and 42%)
- Febrile neutropenia (31% and 22%)
- Musculoskeletal pain (30% and 17%)
- Edema (30% and 20%)
- Thrombocytopenia (30% and 27%).
The incidence of serious AEs was 79% in the glasdegib arm. The most common serious AEs occurring in at least 5% of patients in this arm were febrile neutropenia (29%), pneumonia (23%), hemorrhage (12%), anemia (7%), and sepsis (7%).
Additional data from this trial are included in the prescribing information for glasdegib. Glasdegib is a product of Pfizer.
FDA approves first treatment for primary HLH
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
The U.S. Food and Drug Administration (FDA) has approved emapalumab-lzsg (Gamifant®) to treat primary hemophagocytic lymphohistiocytosis (HLH).
Emapalumab, an interferon gamma-blocking antibody, is approved to treat to treat patients of all ages (newborn and older) with primary HLH who have refractory, recurrent, or progressive disease or who cannot tolerate conventional HLH therapy.
Emapalumab is the first treatment to be FDA-approved for primary HLH, and it is expected to be available in the United States in the first quarter of 2019.
The FDA previously granted emapalumab priority review, breakthrough therapy designation, orphan drug designation, and rare pediatric disease designation.
The FDA’s approval of emapalumab is based on results from a phase 2/3 trial (NCT01818492).
The trial included 34 patients, 27 of whom had refractory, recurrent, or progressive disease or could not tolerate conventional HLH therapy.
Patients received emapalumab in combination with dexamethasone.
At the end of treatment, 63% (17/27) of patients had achieved a response, which was defined as complete response (n=7), partial response (n=8), or HLH improvement (n=2).
Seventy percent (n=19) of patients went on to hematopoietic stem cell transplant.
The most common adverse events were infections (56%), hypertension (41%), infusion-related reactions (27%), and pyrexia (24%).
Additional results from this study can be found in the prescribing information for emapalumab, which is available at www.gamifant.com.
Results are also scheduled to be presented at the 2018 ASH Annual Meeting (abstract LBA-6).
Emapalumab was developed by Novimmune SA. Sobi acquired global rights to the drug in August 2018.
Triplet produces ‘unprecedented’ ORR in PI-refractory MM
Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).
The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.
In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.1,2,3
“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.
The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.
For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.
The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).
All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.
All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.
In this study, the patients received:
- Nelfinavir at 2500 mg on days 1 to 14 twice daily
- Bortezomib at 1.3 mg/m2 subcutaneously on days 1, 4, 8, and 11
- Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.
The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).
Results
The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.
The ORR (PR or better) was:
- 77% in patients with poor-risk cytogenetics
- 67% in patients with fewer than five prior therapies
- 63% in patients with five or more prior therapies
- 70% in patients refractory to bortezomib and lenalidomide
- 60% in patients refractory to bortezomib and pomalidomide
- 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.
The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.
“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.
Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.
The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.
The median overall survival was 12 months, and 17 patients had died as of November 2016.
The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).
There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.
“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.
This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.
Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.
1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.
2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.
Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).
The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.
In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.1,2,3
“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.
The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.
For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.
The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).
All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.
All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.
In this study, the patients received:
- Nelfinavir at 2500 mg on days 1 to 14 twice daily
- Bortezomib at 1.3 mg/m2 subcutaneously on days 1, 4, 8, and 11
- Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.
The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).
Results
The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.
The ORR (PR or better) was:
- 77% in patients with poor-risk cytogenetics
- 67% in patients with fewer than five prior therapies
- 63% in patients with five or more prior therapies
- 70% in patients refractory to bortezomib and lenalidomide
- 60% in patients refractory to bortezomib and pomalidomide
- 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.
The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.
“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.
Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.
The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.
The median overall survival was 12 months, and 17 patients had died as of November 2016.
The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).
There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.
“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.
This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.
Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.
1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.
2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.
Phase 2 results suggest a three-drug regimen may improve response rates in patients with proteasome inhibitor (PI)-refractory multiple myeloma (MM).
The combination—nelfinavir, bortezomib, and dexamethasone (NeVd)—produced an objective response rate (ORR) of 65% in this trial.
In comparison, past studies have shown response rates of 24% to 36% in the PI-refractory MM population.1,2,3
“The unprecedented ORR of NeVd observed in this heavily pretreated, multi-refractory setting warrants further investigation to explore the potential of nelfinavir in combination with PIs . . . ,” Christoph Driessen, of Kantonsspital St. Gallen in Switzerland, and his colleagues wrote in a letter to Blood.
The researchers noted that NeVd previously demonstrated activity in a phase 1 trial of MM patients who were refractory to both bortezomib and lenalidomide.
For the phase 2 study (NCT02188537), Dr. Driessen and his colleagues tested NeVd in MM patients who were refractory to their most recent PI-containing regimen and were previously exposed to or intolerant of at least one immunomodulatory drug.
The 34 patients had a median age of 67 (range, 42-82). Sixty-two percent were male, 38% had poor-risk cytogenetics, and most had a performance status of 0 (59%) or 1 (32%).
All patients had received lenalidomide, 47% had prior pomalidomide, 76% had prior high-dose chemotherapy, and 76% had a prior transplant.
All patients were bortezomib-refractory, 79% were refractory to a PI and lenalidomide, 44% were refractory to a PI and pomalidomide, and 38% were refractory to a PI, lenalidomide, and pomalidomide.
In this study, the patients received:
- Nelfinavir at 2500 mg on days 1 to 14 twice daily
- Bortezomib at 1.3 mg/m2 subcutaneously on days 1, 4, 8, and 11
- Dexamethasone at 20 mg orally on days 1 to 2, 4 to 5, 8 to 9, and 11 to 12.
The patients were treated for up to six 21-day cycles. They received a median of 4.5 cycles (range, 1-6).
Results
The ORR was 65%, with 17 partial responses (PRs) and five very good PRs. Three patients had a minimal response, and four had stable disease.
The ORR (PR or better) was:
- 77% in patients with poor-risk cytogenetics
- 67% in patients with fewer than five prior therapies
- 63% in patients with five or more prior therapies
- 70% in patients refractory to bortezomib and lenalidomide
- 60% in patients refractory to bortezomib and pomalidomide
- 62% in patients refractory to bortezomib, lenalidomide, and pomalidomide.
The researchers said the clinical benefit of NeVd may have been underestimated in this trial because patients were only able to receive six cycles of treatment on study due to a lack of external funding support.
“The time course of paraprotein levels also suggests that individual patients might potentially have experienced myeloma control if NeVd had been continued until progression,” the researchers wrote.
Five patients did receive more than six cycles of NeVd on a compassionate-use basis. In all, 27 patients received additional anti-myeloma treatment during follow-up.
The median progression-free survival was 12 weeks for the entire cohort and 16 weeks among patients who achieved a PR or better.
The median overall survival was 12 months, and 17 patients had died as of November 2016.
The researchers said the most common adverse events in this trial were anemia (97%), thrombocytopenia (82%), hypertension (53%), diarrhea (47%), fatigue (38%), and dyspnea (35%).
There were four deaths during treatment—three due to septicemia and one from heart failure. Three of the deaths were associated with underlying pneumonia.
“Although this mortality rate is consistent with the background mortality among patients with heavily pretreated, refractory myeloma, these findings suggest that prophylactic antibiotic therapy should be considered in those with low neutrophil counts and/or advanced age undergoing NeVd treatment,” the researchers wrote.
This work was supported by the Swiss Group for Clinical Cancer Research, the Swiss State Secretariat for Education, Research and Innovation, the Rising Tide Foundation for Clinical Cancer Research, and the Gateway for Cancer Research.
Most of the researchers declared no competing financial interests, but one reported personal fees from Celgene, Takeda, Amgen, Novartis, and Janssen-Cilag that were unrelated to this trial.
1. Lokhorst HM et al. N Engl J Med. 2015; 373(13):1207-1219.
2. Dimopoulos MA et al. Blood. 2016;128(4): 497-503.
Education can improve adherence to VTE prophylaxis
Education can improve adherence to venous thromboembolism (VTE) prophylaxis among hospitalized patients, according to researchers.
They assessed data from more than 19,000 hospital stays and found that “real-time” educational interventions directed toward patients and nurses significantly reduced nonadministration of prescribed VTE prophylaxis.
However, this did not translate to a significant reduction in VTE incidence.
Elliott Haut, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in JAMA Network Open.
For this study, the researchers evaluated patients who were prescribed VTE prophylaxis while admitted to Johns Hopkins Hospital between April 1, 2015, and December 31, 2015.
The researchers evaluated patients in 16 hospital units. Four units were targeted for educational intervention, and the remaining 12 units served as controls.
The educational interventions were given only when patients did not receive prescribed VTE prophylaxis. A bedside nurse would document nonadministration, and an alert built into the hospital’s electronic medical record would email and page a health educator.
If the patient had refused prophylaxis, the patient would receive an educational bundle on VTE, which could consist of any or all of the following (patient’s choice):
- A one-on-one discussion with the health educator
- A two-page paper handout (available in eight languages)
- A 10-minute educational video (on a tablet).
If the nonadministration of prophylaxis was not due to patient refusal or contraindication, the health educator would educate the bedside nurse about the importance of giving all prescribed doses of VTE prophylaxis.
The study included 19,652 patient visits during which VTE prophylaxis was prescribed.
Of these, 726 visits were targeted for educational intervention. In 272 visits, the intervention was administered to a nurse alone (n=45) or the nurse and the patient (n=227).
For the remaining 454 visits, the patient was discharged before the intervention (n=123), there was an order to discontinue prophylaxis (n=111), there was a technical error (n=55), the patient (n=43) or health educator (n=41) was off unit, or “other” reasons (n=81).
Results
The proportion of nonadministered doses of VTE prophylaxis declined significantly in the hospital units targeted with educational intervention—from 9.1% pre-intervention to 5.6% post-intervention (odds ratio [OR]=0.57, P<0.001).
However, there was no significant change in the control units—13.6% and 13.3%, respectively (OR=0.98, P=0.62).
The proportion of nonadministered doses for reasons other than patient refusal decreased significantly in the intervention units—from 2.3% to 1.7% (OR, 0.74, P=0.01)—but not in control units—from 3.4% to 3.3% (OR=0.98, P=0.69).
The proportion of nonadministered doses due to patient refusal decreased significantly in the intervention units—from 5.9% to 3.4% (OR=0.53, P<0.001)—but not in control units—from 8.7% to 8.5% (OR=0.98, P=0.71).
“Our study demonstrates that educating patients quickly, as soon as we learn about a missed dose, is not only possible to implement at a large hospital but is effective in ensuring that patients take the drugs that can save their lives,” Dr. Haut said.
“The educational bundles we created are effective and optimize busy clinicians’ already packed schedules,” added study author Brandyn Lau, of the Johns Hopkins University School of Medicine.
“At the end of the day, we’re here to deliver high quality care and keep patients safe, and this is one method of achieving that mission.”
However, the improved adherence to VTE prophylaxis did not translate to a significant reduction in VTE in this study.
The incidence of VTE decreased from 0.30% to 0.18% (OR=0.60) in intervention units and from 0.24% to 0.20% in control units (OR=0.81).
For all patients, the incidence of VTE was 0.26% pre-intervention and 0.19% post-intervention (P=0.46).
This research was supported by a contract from the Patient-Centered Outcomes Research Institute. The study authors reported support from various government agencies and private organizations.
Education can improve adherence to venous thromboembolism (VTE) prophylaxis among hospitalized patients, according to researchers.
They assessed data from more than 19,000 hospital stays and found that “real-time” educational interventions directed toward patients and nurses significantly reduced nonadministration of prescribed VTE prophylaxis.
However, this did not translate to a significant reduction in VTE incidence.
Elliott Haut, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in JAMA Network Open.
For this study, the researchers evaluated patients who were prescribed VTE prophylaxis while admitted to Johns Hopkins Hospital between April 1, 2015, and December 31, 2015.
The researchers evaluated patients in 16 hospital units. Four units were targeted for educational intervention, and the remaining 12 units served as controls.
The educational interventions were given only when patients did not receive prescribed VTE prophylaxis. A bedside nurse would document nonadministration, and an alert built into the hospital’s electronic medical record would email and page a health educator.
If the patient had refused prophylaxis, the patient would receive an educational bundle on VTE, which could consist of any or all of the following (patient’s choice):
- A one-on-one discussion with the health educator
- A two-page paper handout (available in eight languages)
- A 10-minute educational video (on a tablet).
If the nonadministration of prophylaxis was not due to patient refusal or contraindication, the health educator would educate the bedside nurse about the importance of giving all prescribed doses of VTE prophylaxis.
The study included 19,652 patient visits during which VTE prophylaxis was prescribed.
Of these, 726 visits were targeted for educational intervention. In 272 visits, the intervention was administered to a nurse alone (n=45) or the nurse and the patient (n=227).
For the remaining 454 visits, the patient was discharged before the intervention (n=123), there was an order to discontinue prophylaxis (n=111), there was a technical error (n=55), the patient (n=43) or health educator (n=41) was off unit, or “other” reasons (n=81).
Results
The proportion of nonadministered doses of VTE prophylaxis declined significantly in the hospital units targeted with educational intervention—from 9.1% pre-intervention to 5.6% post-intervention (odds ratio [OR]=0.57, P<0.001).
However, there was no significant change in the control units—13.6% and 13.3%, respectively (OR=0.98, P=0.62).
The proportion of nonadministered doses for reasons other than patient refusal decreased significantly in the intervention units—from 2.3% to 1.7% (OR, 0.74, P=0.01)—but not in control units—from 3.4% to 3.3% (OR=0.98, P=0.69).
The proportion of nonadministered doses due to patient refusal decreased significantly in the intervention units—from 5.9% to 3.4% (OR=0.53, P<0.001)—but not in control units—from 8.7% to 8.5% (OR=0.98, P=0.71).
“Our study demonstrates that educating patients quickly, as soon as we learn about a missed dose, is not only possible to implement at a large hospital but is effective in ensuring that patients take the drugs that can save their lives,” Dr. Haut said.
“The educational bundles we created are effective and optimize busy clinicians’ already packed schedules,” added study author Brandyn Lau, of the Johns Hopkins University School of Medicine.
“At the end of the day, we’re here to deliver high quality care and keep patients safe, and this is one method of achieving that mission.”
However, the improved adherence to VTE prophylaxis did not translate to a significant reduction in VTE in this study.
The incidence of VTE decreased from 0.30% to 0.18% (OR=0.60) in intervention units and from 0.24% to 0.20% in control units (OR=0.81).
For all patients, the incidence of VTE was 0.26% pre-intervention and 0.19% post-intervention (P=0.46).
This research was supported by a contract from the Patient-Centered Outcomes Research Institute. The study authors reported support from various government agencies and private organizations.
Education can improve adherence to venous thromboembolism (VTE) prophylaxis among hospitalized patients, according to researchers.
They assessed data from more than 19,000 hospital stays and found that “real-time” educational interventions directed toward patients and nurses significantly reduced nonadministration of prescribed VTE prophylaxis.
However, this did not translate to a significant reduction in VTE incidence.
Elliott Haut, MD, PhD, of the Johns Hopkins University School of Medicine in Baltimore, Maryland, and his colleagues reported these results in JAMA Network Open.
For this study, the researchers evaluated patients who were prescribed VTE prophylaxis while admitted to Johns Hopkins Hospital between April 1, 2015, and December 31, 2015.
The researchers evaluated patients in 16 hospital units. Four units were targeted for educational intervention, and the remaining 12 units served as controls.
The educational interventions were given only when patients did not receive prescribed VTE prophylaxis. A bedside nurse would document nonadministration, and an alert built into the hospital’s electronic medical record would email and page a health educator.
If the patient had refused prophylaxis, the patient would receive an educational bundle on VTE, which could consist of any or all of the following (patient’s choice):
- A one-on-one discussion with the health educator
- A two-page paper handout (available in eight languages)
- A 10-minute educational video (on a tablet).
If the nonadministration of prophylaxis was not due to patient refusal or contraindication, the health educator would educate the bedside nurse about the importance of giving all prescribed doses of VTE prophylaxis.
The study included 19,652 patient visits during which VTE prophylaxis was prescribed.
Of these, 726 visits were targeted for educational intervention. In 272 visits, the intervention was administered to a nurse alone (n=45) or the nurse and the patient (n=227).
For the remaining 454 visits, the patient was discharged before the intervention (n=123), there was an order to discontinue prophylaxis (n=111), there was a technical error (n=55), the patient (n=43) or health educator (n=41) was off unit, or “other” reasons (n=81).
Results
The proportion of nonadministered doses of VTE prophylaxis declined significantly in the hospital units targeted with educational intervention—from 9.1% pre-intervention to 5.6% post-intervention (odds ratio [OR]=0.57, P<0.001).
However, there was no significant change in the control units—13.6% and 13.3%, respectively (OR=0.98, P=0.62).
The proportion of nonadministered doses for reasons other than patient refusal decreased significantly in the intervention units—from 2.3% to 1.7% (OR, 0.74, P=0.01)—but not in control units—from 3.4% to 3.3% (OR=0.98, P=0.69).
The proportion of nonadministered doses due to patient refusal decreased significantly in the intervention units—from 5.9% to 3.4% (OR=0.53, P<0.001)—but not in control units—from 8.7% to 8.5% (OR=0.98, P=0.71).
“Our study demonstrates that educating patients quickly, as soon as we learn about a missed dose, is not only possible to implement at a large hospital but is effective in ensuring that patients take the drugs that can save their lives,” Dr. Haut said.
“The educational bundles we created are effective and optimize busy clinicians’ already packed schedules,” added study author Brandyn Lau, of the Johns Hopkins University School of Medicine.
“At the end of the day, we’re here to deliver high quality care and keep patients safe, and this is one method of achieving that mission.”
However, the improved adherence to VTE prophylaxis did not translate to a significant reduction in VTE in this study.
The incidence of VTE decreased from 0.30% to 0.18% (OR=0.60) in intervention units and from 0.24% to 0.20% in control units (OR=0.81).
For all patients, the incidence of VTE was 0.26% pre-intervention and 0.19% post-intervention (P=0.46).
This research was supported by a contract from the Patient-Centered Outcomes Research Institute. The study authors reported support from various government agencies and private organizations.
Score can predict thrombosis in ITP
New research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score identified all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly—within a matter of days—which suggests they should be re-evaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ontario, Canada, and her colleagues detailed this research in Blood.
About the score
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The resulting score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L
- Major bleeding (grade 2 bleeding that does not involve the skin) observed at a clinical encounter.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests a net increased risk of thrombosis, and a negative score suggests a net increased risk of bleeding.
Patient population
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months (interquartile range, 4.5 to 24 months). During that time, there were 41 clinical encounters. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld at some point during their 22 clinical encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
The remaining three patients (of the 13) did not stop anticoagulation. These patients received additional ITP treatments at six of their 10 clinical encounters.
Major bleeding was present at two of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
Testing the score
The TH2 score accurately predicted all seven thrombotic events.
There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score—suggesting an increased risk of thrombosis—when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be re-evaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number of patients evaluated. Therefore, the TH2 score should be validated in additional, larger studies.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma. The other researchers said they had no competing financial interests.
New research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score identified all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly—within a matter of days—which suggests they should be re-evaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ontario, Canada, and her colleagues detailed this research in Blood.
About the score
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The resulting score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L
- Major bleeding (grade 2 bleeding that does not involve the skin) observed at a clinical encounter.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests a net increased risk of thrombosis, and a negative score suggests a net increased risk of bleeding.
Patient population
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months (interquartile range, 4.5 to 24 months). During that time, there were 41 clinical encounters. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld at some point during their 22 clinical encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
The remaining three patients (of the 13) did not stop anticoagulation. These patients received additional ITP treatments at six of their 10 clinical encounters.
Major bleeding was present at two of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
Testing the score
The TH2 score accurately predicted all seven thrombotic events.
There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score—suggesting an increased risk of thrombosis—when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be re-evaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number of patients evaluated. Therefore, the TH2 score should be validated in additional, larger studies.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma. The other researchers said they had no competing financial interests.
New research suggests a scoring system can predict the risk of thrombosis in patients with immune thrombocytopenia (ITP) who are taking anticoagulants.
Researchers tested their Thrombosis and Thrombocytopenia (TH2) risk assessment score in a small group of ITP patients on anticoagulants, and the score identified all seven patients who developed thrombosis.
The researchers also found that patients’ TH2 scores changed quickly—within a matter of days—which suggests they should be re-evaluated for thrombosis risk frequently.
Amaris K. Balitsky, MD, of McMaster University in Hamilton, Ontario, Canada, and her colleagues detailed this research in Blood.
About the score
To develop the TH2 score, the researchers conducted a review of the literature and existing tools used to assess the risk of thrombosis and bleeding. The resulting score consists of two thrombosis items and two bleeding items.
The thrombosis items are:
- High thrombotic risk, which includes patients with atrial fibrillation and a CHA2DS2-VASc score greater than five; unprovoked, recurrent, or cancer-associated thrombosis; or antiphospholipid antibody syndrome
- Receipt of ITP therapies known to increase the risk of thrombosis in the previous 14 days or splenectomy in the previous 30 days.
The score’s bleeding items are:
- Platelet count less than 20 x 109/L
- Major bleeding (grade 2 bleeding that does not involve the skin) observed at a clinical encounter.
Each thrombosis item is assigned a score of +1, and each bleeding item is assigned a score of -1. A positive score or score of 0 suggests a net increased risk of thrombosis, and a negative score suggests a net increased risk of bleeding.
Patient population
The researchers tested the TH2 score in patients enrolled in the McMaster ITP Registry from 2010 to 2017.
There were 314 patients enrolled, but only 13 were receiving anticoagulation and had a platelet count less than 50 x 109/L. Six of these patients were receiving anticoagulation for atrial fibrillation and seven for venous thrombosis. Four patients were taking antiplatelet agents as well.
The median follow up was 9 months (interquartile range, 4.5 to 24 months). During that time, there were 41 clinical encounters. Data on treatment decisions and clinical outcomes were available for 32 of these encounters.
Ten of the 13 patients had anticoagulation withheld at some point during their 22 clinical encounters. Major bleeding was present at five of the encounters. At 17 encounters, patients received additional ITP treatments.
Six of the 10 patients who stopped anticoagulation had new thrombotic events, and two of these events were fatal. Three of the patients had thrombotic events even though they resumed anticoagulation.
The remaining three patients (of the 13) did not stop anticoagulation. These patients received additional ITP treatments at six of their 10 clinical encounters.
Major bleeding was present at two of the 10 encounters, and one new thrombotic event occurred in a patient with metastatic squamous cell cancer (despite continued treatment with warfarin).
Testing the score
The TH2 score accurately predicted all seven thrombotic events.
There were four patients who initially had a negative TH2 score, which suggested an increased risk of bleeding.
However, these patients had a positive or 0 score—suggesting an increased risk of thrombosis—when they were assessed again, after their platelet counts increased above 50 x 109/L.
The remaining three patients had initial scores of 0 and subsequent positive scores, both suggesting an increased risk of thrombosis.
The researchers said these findings suggest patients should be re-evaluated for thrombosis risk frequently, as ITP treatments are given and platelet counts increase.
“The results of our study suggest that the risk of thrombosis is high in patients with ITP who have a separate indication for anticoagulation, especially after ITP therapies are administered and the severe thrombocytopenia improves,” the researchers wrote. “Early resumption of anticoagulation should be considered in this population.”
The researchers also noted that this study was limited by its retrospective, single-center design and the small number of patients evaluated. Therefore, the TH2 score should be validated in additional, larger studies.
One researcher reported relationships with Amgen, Novartis, Rigel Pharmaceuticals, UCB, and Principia Biopharma. The other researchers said they had no competing financial interests.
‘Encouraging’ phase 2 results in rel/ref AML
The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.
The overall response rate was 33%, and the median overall survival (OS) was 6.3 months.
However, the researchers identified factors associated with improved response and survival that they believe could be used to select patients for this treatment.
A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment-related.
Naval Daver, MD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in Cancer Discovery.
The trial included 70 patients with a median age of 70 (range, 22-90). Fifty-six percent had de novo AML, and 44% had secondary AML.
The median number of prior therapies was 2 (range, 1 to 7). Sixty-four percent of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).
For this trial, patients received azacitidine at 75 mg/m2 on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was 3 (range, 1 to 25).
Patients had a median time on study of 3.5 months (range, 0.3 to 26.3 months). Reasons for discontinuation included primary refractory disease (n=27), relapse after initial response (n=19), death (n=16), proceeding to SCT (n=3), and patient preference (n=3).
Safety
The most common treatment-related, non-hematologic AEs were constipation (26%), diarrhea (20%), pneumonitis (13%), nausea (11%), and lung infection (11%).
The rate of immune-related AEs was 25% (n=18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4). Fourteen of these patients responded to steroids and were safely re-challenged with nivolumab, according to the researchers.
Nine patients (13%) discontinued nivolumab (but continued with azacitidine) due to AEs—pneumonitis (n=7), cytokine release syndrome (n=1), and immune nephritis (n=1).
Two patients died of AEs that were considered possibly related to treatment. One death was due to progressive pneumonia/pneumonitis, and one was due to hemophagocytosis lymphohistiocytosis.
Response
The overall response rate was 33% (n=23). Four patients had a complete response (CR), and 11 had a CR with incomplete count recovery (CRi).
One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.
The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. In addition, a higher frequency of pre-therapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.
“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said.
Survival
At a median follow-up of 21.4 months, 81% of patients (n=57) had died. Sixteen patients died on study treatment, and 41 died after discontinuation.
The median OS was 6.3 months, and the median event-free survival was 4.5 months.
The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in non-responders (P<0.0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P<0.001).
The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.
Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.
“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver noted.
This research was supported by Bristol-Myers Squibb, MD Anderson, and the Dick Clark Immunotherapy Research Fund. In addition, individual researchers reported financial relationships with Bristol-Myers Squibb.
The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.
The overall response rate was 33%, and the median overall survival (OS) was 6.3 months.
However, the researchers identified factors associated with improved response and survival that they believe could be used to select patients for this treatment.
A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment-related.
Naval Daver, MD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in Cancer Discovery.
The trial included 70 patients with a median age of 70 (range, 22-90). Fifty-six percent had de novo AML, and 44% had secondary AML.
The median number of prior therapies was 2 (range, 1 to 7). Sixty-four percent of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).
For this trial, patients received azacitidine at 75 mg/m2 on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was 3 (range, 1 to 25).
Patients had a median time on study of 3.5 months (range, 0.3 to 26.3 months). Reasons for discontinuation included primary refractory disease (n=27), relapse after initial response (n=19), death (n=16), proceeding to SCT (n=3), and patient preference (n=3).
Safety
The most common treatment-related, non-hematologic AEs were constipation (26%), diarrhea (20%), pneumonitis (13%), nausea (11%), and lung infection (11%).
The rate of immune-related AEs was 25% (n=18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4). Fourteen of these patients responded to steroids and were safely re-challenged with nivolumab, according to the researchers.
Nine patients (13%) discontinued nivolumab (but continued with azacitidine) due to AEs—pneumonitis (n=7), cytokine release syndrome (n=1), and immune nephritis (n=1).
Two patients died of AEs that were considered possibly related to treatment. One death was due to progressive pneumonia/pneumonitis, and one was due to hemophagocytosis lymphohistiocytosis.
Response
The overall response rate was 33% (n=23). Four patients had a complete response (CR), and 11 had a CR with incomplete count recovery (CRi).
One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.
The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. In addition, a higher frequency of pre-therapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.
“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said.
Survival
At a median follow-up of 21.4 months, 81% of patients (n=57) had died. Sixteen patients died on study treatment, and 41 died after discontinuation.
The median OS was 6.3 months, and the median event-free survival was 4.5 months.
The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in non-responders (P<0.0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P<0.001).
The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.
Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.
“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver noted.
This research was supported by Bristol-Myers Squibb, MD Anderson, and the Dick Clark Immunotherapy Research Fund. In addition, individual researchers reported financial relationships with Bristol-Myers Squibb.
The combination of azacitidine and nivolumab produced “encouraging” results in a phase 2 trial of patients with relapsed or refractory acute myeloid leukemia (AML), according to researchers.
The overall response rate was 33%, and the median overall survival (OS) was 6.3 months.
However, the researchers identified factors associated with improved response and survival that they believe could be used to select patients for this treatment.
A quarter of patients on this trial had immune-related adverse events (AEs) that were considered related to treatment, and two patients died of AEs that may have been treatment-related.
Naval Daver, MD, of The University of Texas MD Anderson Cancer Center in Houston, and his colleagues reported these results in Cancer Discovery.
The trial included 70 patients with a median age of 70 (range, 22-90). Fifty-six percent had de novo AML, and 44% had secondary AML.
The median number of prior therapies was 2 (range, 1 to 7). Sixty-four percent of patients had received hypomethylating agents, 47% had received targeted therapies, and 19% had received allogeneic stem cell transplant (SCT).
For this trial, patients received azacitidine at 75 mg/m2 on days 1 to 7 and nivolumab at 3 mg/kg on days 1 and 14 of each cycle. The median number of cycles was 3 (range, 1 to 25).
Patients had a median time on study of 3.5 months (range, 0.3 to 26.3 months). Reasons for discontinuation included primary refractory disease (n=27), relapse after initial response (n=19), death (n=16), proceeding to SCT (n=3), and patient preference (n=3).
Safety
The most common treatment-related, non-hematologic AEs were constipation (26%), diarrhea (20%), pneumonitis (13%), nausea (11%), and lung infection (11%).
The rate of immune-related AEs was 25% (n=18), with grade 2-4 immune-related AEs occurring in 16 patients (8 with grade 3-4). Fourteen of these patients responded to steroids and were safely re-challenged with nivolumab, according to the researchers.
Nine patients (13%) discontinued nivolumab (but continued with azacitidine) due to AEs—pneumonitis (n=7), cytokine release syndrome (n=1), and immune nephritis (n=1).
Two patients died of AEs that were considered possibly related to treatment. One death was due to progressive pneumonia/pneumonitis, and one was due to hemophagocytosis lymphohistiocytosis.
Response
The overall response rate was 33% (n=23). Four patients had a complete response (CR), and 11 had a CR with incomplete count recovery (CRi).
One patient had a partial response, and seven had hematologic improvement in one or more parameter maintained for more than 6 months. Six patients had stable disease lasting more than 6 months.
The researchers noted that the response rate was higher among patients who had not received prior treatment with hypomethylating agents. In addition, a higher frequency of pre-therapy CD3 and CD8 cells in the bone marrow or peripheral blood appeared to predict response.
“In particular, CD3 appeared to have a high sensitivity and specificity rate for predicting response, indicating it might serve as a reliable biomarker for selecting patients for this combination therapy,” Dr. Daver said.
Survival
At a median follow-up of 21.4 months, 81% of patients (n=57) had died. Sixteen patients died on study treatment, and 41 died after discontinuation.
The median OS was 6.3 months, and the median event-free survival was 4.5 months.
The median OS was 16.1 months in patients with CR/CRi, partial response, hematologic improvement, or stable disease and 4.1 months in non-responders (P<0.0001). This difference was still significant after the researchers censored the three patients who had gone on to SCT in CR/CRi (P<0.001).
The researchers also found that being in first salvage was associated with improved OS in a univariate analysis and in a comparison with historical controls.
Dr. Daver and his colleagues concluded that azacitidine and nivolumab “produced an encouraging response rate and overall survival” in patients with relapsed/refractory AML.
“We believe that implementation of clinical and immune biomarkers to select patients are likely to yield further improved outcomes with these types of therapies in AML,” Dr. Daver noted.
This research was supported by Bristol-Myers Squibb, MD Anderson, and the Dick Clark Immunotherapy Research Fund. In addition, individual researchers reported financial relationships with Bristol-Myers Squibb.