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Combo treatment may improve quality of life in CTCL
LA JOLLA, CALIF. — Treatment with brentuximab vedotin (BV) and lenalidomide (len) may improve quality of life (QOL) for patients with cutaneous T-cell lymphoma (CTCL), according to the principal investigator of a phase 2 trial.
In this small trial, most CTCL patients experienced relief from pruritus after one cycle of treatment with BV-len.
Investigators also observed durable responses to the combination, although two patients experienced tumor flare prior to response.
“Because of the tumor flare, we decreased the dose of lenalidomide ... and, since then, it has not been a major problem,” said Basem M. William, MD, principal investigator of the trial and a professor at Ohio State University in Columbus.
“We’re trying to be more reassuring to patients that, if they experience a little bit of tumor flare, as long as it’s not dangerous or life-threatening, if they can hold on with the treatment, this might translate to a later durable response.”
Dr. William and his colleagues presented results from this ongoing, phase 2 trial (NCT03409432) at the annual T-cell Lymphoma Forum.
Thus far, the investigators have treated 12 patients with relapsed or refractory CTCL or peripheral T-cell lymphoma (PTCL). The CTCL patients had received at least two lines of skin-directed therapy or one line of systemic therapy, and the PTCL patients had received at least one line of systemic therapy.
Dr. William and his colleagues reported results for 10 patients. Six patients had mycosis fungoides (MF), two had Sézary syndrome (SS), one had CD30+ lymphoproliferative disorder, and one had systemic anaplastic large-cell lymphoma (ALCL).
The patients’ median age was 59 (range, 49-74), there were nine males, and patients had received a median of 2 (range, 1-10) prior therapies.
The first seven patients received BV at 1.2 mg/kg and len at 20 mg daily every 3 weeks. However, after the investigators observed tumor flare in two patients, the dose of len was lowered to 10 mg.
Safety
The investigators said all adverse events (AEs) were reversible by stopping therapy, there were no grade 4 AEs, and none of the patients had grade 3 or higher neuropathy.
“We have not seen an excess of neuropathy, which is very important because both brentuximab and lenalidomide are known to cause neuropathy,” Dr. William said. “So we were fairly concerned that there would be a synergistic neurotoxic effect, which we don’t want, but we haven’t seen that.”
The most common treatment-related AE was neutropenia. Grade 3 neutropenia occurred in four patients.
Other grade 3 AEs, which occurred in patients on the 20 mg dose of len, were thrombocytopenia (n = 1), dyspnea (n = 1), vertigo (n = 1), drug rash with eosinophilia and systemic symptoms (DRESS) syndrome (n = 1), and tumor flare (n = 1).
Three patients discontinued treatment because of AEs — thrombocytopenia, tumor flare, and DRESS syndrome.
Tumor flare and response
“We did see tumor flare in two initial patients treated with the higher dose of lenalidomide, and we had to remove them from the study for their safety,” Dr. William said. “One of them had a full-blown DRESS syndrome. For their safety, we did have to remove them, but both did experience durable remissions after.”
One of the patients with tumor flare, who had MF, didn’t require treatment for 6 months after going off study. The other patient, who had SS, cleared the clone from his blood but developed DRESS syndrome.
In all, three patients achieved a response to treatment. The ALCL patient had a complete response, and two MF patients achieved a partial response.
Two MF patients and one SS patient had stable disease. The remaining four patients — two with MF, one with SS, and one with lymphoproliferative disorder — progressed.
QOL
The investigators used the Skindex-16 to assess the effect of treatment on QOL.
Five of six evaluable patients with CTCL had a 50% or greater reduction in their Skindex-16 scores after two cycles of treatment. In fact, most patients had relief from pruritus after one cycle, Dr. William said.
“Patients with cutaneous T-cell lymphoma, their biggest problem is with the symptom burden, with pruritus,” he said. “They’re really miserable from all the itching they have. They cannot sleep at night. So we’re fairly excited that most of the patients we’ve treated so far had relief from pruritus just after one cycle.”
Dr. William said he and his colleagues are excited about the overall results they have observed with BV-len, although it’s “still pretty early” in the trial. The investigators are planning to enroll a total of 42 patients and may open the trial at a second center.
The study is sponsored by Ohio State University and the lenalidomide is provided by Celgene. Dr. William reported relationships with miRagen Therapeutics, GuidePoint, Kyowa Kirin, and Celgene.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. — Treatment with brentuximab vedotin (BV) and lenalidomide (len) may improve quality of life (QOL) for patients with cutaneous T-cell lymphoma (CTCL), according to the principal investigator of a phase 2 trial.
In this small trial, most CTCL patients experienced relief from pruritus after one cycle of treatment with BV-len.
Investigators also observed durable responses to the combination, although two patients experienced tumor flare prior to response.
“Because of the tumor flare, we decreased the dose of lenalidomide ... and, since then, it has not been a major problem,” said Basem M. William, MD, principal investigator of the trial and a professor at Ohio State University in Columbus.
“We’re trying to be more reassuring to patients that, if they experience a little bit of tumor flare, as long as it’s not dangerous or life-threatening, if they can hold on with the treatment, this might translate to a later durable response.”
Dr. William and his colleagues presented results from this ongoing, phase 2 trial (NCT03409432) at the annual T-cell Lymphoma Forum.
Thus far, the investigators have treated 12 patients with relapsed or refractory CTCL or peripheral T-cell lymphoma (PTCL). The CTCL patients had received at least two lines of skin-directed therapy or one line of systemic therapy, and the PTCL patients had received at least one line of systemic therapy.
Dr. William and his colleagues reported results for 10 patients. Six patients had mycosis fungoides (MF), two had Sézary syndrome (SS), one had CD30+ lymphoproliferative disorder, and one had systemic anaplastic large-cell lymphoma (ALCL).
The patients’ median age was 59 (range, 49-74), there were nine males, and patients had received a median of 2 (range, 1-10) prior therapies.
The first seven patients received BV at 1.2 mg/kg and len at 20 mg daily every 3 weeks. However, after the investigators observed tumor flare in two patients, the dose of len was lowered to 10 mg.
Safety
The investigators said all adverse events (AEs) were reversible by stopping therapy, there were no grade 4 AEs, and none of the patients had grade 3 or higher neuropathy.
“We have not seen an excess of neuropathy, which is very important because both brentuximab and lenalidomide are known to cause neuropathy,” Dr. William said. “So we were fairly concerned that there would be a synergistic neurotoxic effect, which we don’t want, but we haven’t seen that.”
The most common treatment-related AE was neutropenia. Grade 3 neutropenia occurred in four patients.
Other grade 3 AEs, which occurred in patients on the 20 mg dose of len, were thrombocytopenia (n = 1), dyspnea (n = 1), vertigo (n = 1), drug rash with eosinophilia and systemic symptoms (DRESS) syndrome (n = 1), and tumor flare (n = 1).
Three patients discontinued treatment because of AEs — thrombocytopenia, tumor flare, and DRESS syndrome.
Tumor flare and response
“We did see tumor flare in two initial patients treated with the higher dose of lenalidomide, and we had to remove them from the study for their safety,” Dr. William said. “One of them had a full-blown DRESS syndrome. For their safety, we did have to remove them, but both did experience durable remissions after.”
One of the patients with tumor flare, who had MF, didn’t require treatment for 6 months after going off study. The other patient, who had SS, cleared the clone from his blood but developed DRESS syndrome.
In all, three patients achieved a response to treatment. The ALCL patient had a complete response, and two MF patients achieved a partial response.
Two MF patients and one SS patient had stable disease. The remaining four patients — two with MF, one with SS, and one with lymphoproliferative disorder — progressed.
QOL
The investigators used the Skindex-16 to assess the effect of treatment on QOL.
Five of six evaluable patients with CTCL had a 50% or greater reduction in their Skindex-16 scores after two cycles of treatment. In fact, most patients had relief from pruritus after one cycle, Dr. William said.
“Patients with cutaneous T-cell lymphoma, their biggest problem is with the symptom burden, with pruritus,” he said. “They’re really miserable from all the itching they have. They cannot sleep at night. So we’re fairly excited that most of the patients we’ve treated so far had relief from pruritus just after one cycle.”
Dr. William said he and his colleagues are excited about the overall results they have observed with BV-len, although it’s “still pretty early” in the trial. The investigators are planning to enroll a total of 42 patients and may open the trial at a second center.
The study is sponsored by Ohio State University and the lenalidomide is provided by Celgene. Dr. William reported relationships with miRagen Therapeutics, GuidePoint, Kyowa Kirin, and Celgene.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. — Treatment with brentuximab vedotin (BV) and lenalidomide (len) may improve quality of life (QOL) for patients with cutaneous T-cell lymphoma (CTCL), according to the principal investigator of a phase 2 trial.
In this small trial, most CTCL patients experienced relief from pruritus after one cycle of treatment with BV-len.
Investigators also observed durable responses to the combination, although two patients experienced tumor flare prior to response.
“Because of the tumor flare, we decreased the dose of lenalidomide ... and, since then, it has not been a major problem,” said Basem M. William, MD, principal investigator of the trial and a professor at Ohio State University in Columbus.
“We’re trying to be more reassuring to patients that, if they experience a little bit of tumor flare, as long as it’s not dangerous or life-threatening, if they can hold on with the treatment, this might translate to a later durable response.”
Dr. William and his colleagues presented results from this ongoing, phase 2 trial (NCT03409432) at the annual T-cell Lymphoma Forum.
Thus far, the investigators have treated 12 patients with relapsed or refractory CTCL or peripheral T-cell lymphoma (PTCL). The CTCL patients had received at least two lines of skin-directed therapy or one line of systemic therapy, and the PTCL patients had received at least one line of systemic therapy.
Dr. William and his colleagues reported results for 10 patients. Six patients had mycosis fungoides (MF), two had Sézary syndrome (SS), one had CD30+ lymphoproliferative disorder, and one had systemic anaplastic large-cell lymphoma (ALCL).
The patients’ median age was 59 (range, 49-74), there were nine males, and patients had received a median of 2 (range, 1-10) prior therapies.
The first seven patients received BV at 1.2 mg/kg and len at 20 mg daily every 3 weeks. However, after the investigators observed tumor flare in two patients, the dose of len was lowered to 10 mg.
Safety
The investigators said all adverse events (AEs) were reversible by stopping therapy, there were no grade 4 AEs, and none of the patients had grade 3 or higher neuropathy.
“We have not seen an excess of neuropathy, which is very important because both brentuximab and lenalidomide are known to cause neuropathy,” Dr. William said. “So we were fairly concerned that there would be a synergistic neurotoxic effect, which we don’t want, but we haven’t seen that.”
The most common treatment-related AE was neutropenia. Grade 3 neutropenia occurred in four patients.
Other grade 3 AEs, which occurred in patients on the 20 mg dose of len, were thrombocytopenia (n = 1), dyspnea (n = 1), vertigo (n = 1), drug rash with eosinophilia and systemic symptoms (DRESS) syndrome (n = 1), and tumor flare (n = 1).
Three patients discontinued treatment because of AEs — thrombocytopenia, tumor flare, and DRESS syndrome.
Tumor flare and response
“We did see tumor flare in two initial patients treated with the higher dose of lenalidomide, and we had to remove them from the study for their safety,” Dr. William said. “One of them had a full-blown DRESS syndrome. For their safety, we did have to remove them, but both did experience durable remissions after.”
One of the patients with tumor flare, who had MF, didn’t require treatment for 6 months after going off study. The other patient, who had SS, cleared the clone from his blood but developed DRESS syndrome.
In all, three patients achieved a response to treatment. The ALCL patient had a complete response, and two MF patients achieved a partial response.
Two MF patients and one SS patient had stable disease. The remaining four patients — two with MF, one with SS, and one with lymphoproliferative disorder — progressed.
QOL
The investigators used the Skindex-16 to assess the effect of treatment on QOL.
Five of six evaluable patients with CTCL had a 50% or greater reduction in their Skindex-16 scores after two cycles of treatment. In fact, most patients had relief from pruritus after one cycle, Dr. William said.
“Patients with cutaneous T-cell lymphoma, their biggest problem is with the symptom burden, with pruritus,” he said. “They’re really miserable from all the itching they have. They cannot sleep at night. So we’re fairly excited that most of the patients we’ve treated so far had relief from pruritus just after one cycle.”
Dr. William said he and his colleagues are excited about the overall results they have observed with BV-len, although it’s “still pretty early” in the trial. The investigators are planning to enroll a total of 42 patients and may open the trial at a second center.
The study is sponsored by Ohio State University and the lenalidomide is provided by Celgene. Dr. William reported relationships with miRagen Therapeutics, GuidePoint, Kyowa Kirin, and Celgene.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Key clinical point:
Major finding: Five of six evaluable CTCL patients had a 50% or greater reduction in their Skindex-16 scores after two cycles of treatment.
Study details: A phase 2 study with results reported for 10 patients.
Disclosures: The study is sponsored by Ohio State University and the lenalidomide is provided by Celgene. The principal investigator reported relationships with miRagen Therapeutics, GuidePoint, Kyowa Kirin, and Celgene.
Are single agents better than chemo for relapsed/refractory PTCL?
LA JOLLA, CALIF. — Results from the COMPLETE registry suggest newer single agents may be more effective than combination chemotherapy for patients with relapsed/refractory peripheral T-cell lymphoma (PTCL).
Complete response (CR) rates and median survival times were significantly better among patients who received single agents than among those who received combination therapy.
Although researchers don’t know what is driving these differences in outcomes, they did find that outcomes were best among patients who received single-agent brentuximab vedotin (BV), and a disproportionate number of patients received BV.
The researchers also found that patients who received single-agent therapy were more likely to proceed to stem cell transplant.
Therefore, it’s still unclear if single-agent treatment is superior to combination therapy for relapsed/refractory PTCL, according to Robert Stuver, MD, of Beth Israel Deaconess Medical Center in Boston.
Dr. Stuver presented data from the COMPLETE (Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment) registry at the annual T-cell Lymphoma Forum.
The registry (NCT01110733) enrolled patients newly diagnosed with PTCL. Dr. Stuver presented results among patients who had relapsed after, or were refractory to, upfront therapy and went on to receive single-agent therapy or any combination regimen excluding those single agents. Outcome data were collected for 5 years or until death.
Patients and treatment
There were 26 patients in the combination treatment group — 10 with PTCL not otherwise specified (NOS), 6 with angioimmunoblastic T-cell lymphoma (AITL), 5 with natural killer T-cell lymphoma (NKTL), 3 with anaplastic large-cell lymphoma (ALCL), 1 with enteropathy-associated T-cell lymphoma (EATL), and 1 with hepatosplenic T-cell lymphoma (HSTCL).
Patients in the combination group received gemcitabine-based therapy (n = 10), ifosfamide-based therapy (n = 7), platinum-based therapy (n = 4), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like therapy (n = 1), DHAP (dexamethasone, high-dose cytarabine, and cisplatin; n = 1), and other combinations (n = 3).
There were 31 patients in the single-agent group – 13 with PTCL-NOS, 7 with ALCL, 5 with AITL, 2 with EATL, 2 with NKTL, and 2 with HSTCL.
These patients were treated with BV (n = 12), romidepsin (n = 8), pralatrexate (n = 5), alisertib (n = 3), bendamustine (n = 1), denileukin diftitox (n = 1), and lenalidomide (n = 1).
Response
The CR rates were significantly higher among patients who received single-agent treatment than among those who received combination therapy — 41.4% (12/31) and 19.2% (5/26), respectively (P = .02). The partial response rates were 17.2% (5/31) and 26.9% (7/26), respectively. Rates of stable disease were 3.4% (1/31) and 30.8% (8/26), respectively.
Complete responders in the single-agent arm were treated with BV (n = 7), romidepsin (n = 2), pralatrexate (n = 1), alisertib (n = 1), and bendamustine (n = 1). Four of the patients treated with BV had ALCL.
“We had an enrichment of patients treated with brentuximab,” Dr. Stuver said. “So the obvious question this begs is, ‘Are the favorable results that were seen for single agents over combination therapy solely due to patients treated with brentuximab?’ ”
To investigate, Dr. Stuver and his colleagues compared responses among patients who received BV with patients who received other single agents or combination therapies.
The CR rate was 58.3% (7/12) among BV recipients, 29.4% (5/17) among patients who received other single agents, and 19.2% (5/26) among patients who received combination therapy.
“The takeaway here is that, when you do divide the single-agent group into BV and other single agents, you’re seeing that BV is doing much better than every other group,” Dr. Stuver said. “And all the other single agents are doing somewhat similarly to the combination group, although there’s still a 10% difference, 29% versus 19%.”
Survival
The median progression-free survival (PFS) and overall survival (OS) were significantly better among patients who received single-agent therapy. The median PFS was 11.7 months in the single-agent group and 6.7 months in the combination group (P = .0197). The median OS was 38.9 months and 17.1 months, respectively (P = .0170).
A factor that may have affected survival is that patients were more likely to undergo stem cell transplant after single-agent therapy (25.8%, 8/31), compared with those who had received combination therapy (7.7%, 2/26).
Another factor that may have affected the survival differences is the enrichment of patients treated with BV.
The researchers found the median PFS was 11.9 months among BV recipients, 10.4 months among patients who received other single agents, and 6.7 months in the combination-therapy group. The median OS was 44.5 months, 19.1 months, and 17.1 months, respectively.
Dr. Stuver said these results suggest there is a role for single agents as first retreatment in the salvage setting. However, this analysis was limited by the small sample size and the enrichment of patients treated with BV.
Larger, randomized studies are needed to identify the “truly superior” treatment strategy for relapsed/refractory PTCL, Dr. Stuver said.
The COMPLETE registry is sponsored by Spectrum Pharmaceuticals. Dr. Stuver did not declare any conflicts of interest.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. — Results from the COMPLETE registry suggest newer single agents may be more effective than combination chemotherapy for patients with relapsed/refractory peripheral T-cell lymphoma (PTCL).
Complete response (CR) rates and median survival times were significantly better among patients who received single agents than among those who received combination therapy.
Although researchers don’t know what is driving these differences in outcomes, they did find that outcomes were best among patients who received single-agent brentuximab vedotin (BV), and a disproportionate number of patients received BV.
The researchers also found that patients who received single-agent therapy were more likely to proceed to stem cell transplant.
Therefore, it’s still unclear if single-agent treatment is superior to combination therapy for relapsed/refractory PTCL, according to Robert Stuver, MD, of Beth Israel Deaconess Medical Center in Boston.
Dr. Stuver presented data from the COMPLETE (Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment) registry at the annual T-cell Lymphoma Forum.
The registry (NCT01110733) enrolled patients newly diagnosed with PTCL. Dr. Stuver presented results among patients who had relapsed after, or were refractory to, upfront therapy and went on to receive single-agent therapy or any combination regimen excluding those single agents. Outcome data were collected for 5 years or until death.
Patients and treatment
There were 26 patients in the combination treatment group — 10 with PTCL not otherwise specified (NOS), 6 with angioimmunoblastic T-cell lymphoma (AITL), 5 with natural killer T-cell lymphoma (NKTL), 3 with anaplastic large-cell lymphoma (ALCL), 1 with enteropathy-associated T-cell lymphoma (EATL), and 1 with hepatosplenic T-cell lymphoma (HSTCL).
Patients in the combination group received gemcitabine-based therapy (n = 10), ifosfamide-based therapy (n = 7), platinum-based therapy (n = 4), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like therapy (n = 1), DHAP (dexamethasone, high-dose cytarabine, and cisplatin; n = 1), and other combinations (n = 3).
There were 31 patients in the single-agent group – 13 with PTCL-NOS, 7 with ALCL, 5 with AITL, 2 with EATL, 2 with NKTL, and 2 with HSTCL.
These patients were treated with BV (n = 12), romidepsin (n = 8), pralatrexate (n = 5), alisertib (n = 3), bendamustine (n = 1), denileukin diftitox (n = 1), and lenalidomide (n = 1).
Response
The CR rates were significantly higher among patients who received single-agent treatment than among those who received combination therapy — 41.4% (12/31) and 19.2% (5/26), respectively (P = .02). The partial response rates were 17.2% (5/31) and 26.9% (7/26), respectively. Rates of stable disease were 3.4% (1/31) and 30.8% (8/26), respectively.
Complete responders in the single-agent arm were treated with BV (n = 7), romidepsin (n = 2), pralatrexate (n = 1), alisertib (n = 1), and bendamustine (n = 1). Four of the patients treated with BV had ALCL.
“We had an enrichment of patients treated with brentuximab,” Dr. Stuver said. “So the obvious question this begs is, ‘Are the favorable results that were seen for single agents over combination therapy solely due to patients treated with brentuximab?’ ”
To investigate, Dr. Stuver and his colleagues compared responses among patients who received BV with patients who received other single agents or combination therapies.
The CR rate was 58.3% (7/12) among BV recipients, 29.4% (5/17) among patients who received other single agents, and 19.2% (5/26) among patients who received combination therapy.
“The takeaway here is that, when you do divide the single-agent group into BV and other single agents, you’re seeing that BV is doing much better than every other group,” Dr. Stuver said. “And all the other single agents are doing somewhat similarly to the combination group, although there’s still a 10% difference, 29% versus 19%.”
Survival
The median progression-free survival (PFS) and overall survival (OS) were significantly better among patients who received single-agent therapy. The median PFS was 11.7 months in the single-agent group and 6.7 months in the combination group (P = .0197). The median OS was 38.9 months and 17.1 months, respectively (P = .0170).
A factor that may have affected survival is that patients were more likely to undergo stem cell transplant after single-agent therapy (25.8%, 8/31), compared with those who had received combination therapy (7.7%, 2/26).
Another factor that may have affected the survival differences is the enrichment of patients treated with BV.
The researchers found the median PFS was 11.9 months among BV recipients, 10.4 months among patients who received other single agents, and 6.7 months in the combination-therapy group. The median OS was 44.5 months, 19.1 months, and 17.1 months, respectively.
Dr. Stuver said these results suggest there is a role for single agents as first retreatment in the salvage setting. However, this analysis was limited by the small sample size and the enrichment of patients treated with BV.
Larger, randomized studies are needed to identify the “truly superior” treatment strategy for relapsed/refractory PTCL, Dr. Stuver said.
The COMPLETE registry is sponsored by Spectrum Pharmaceuticals. Dr. Stuver did not declare any conflicts of interest.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. — Results from the COMPLETE registry suggest newer single agents may be more effective than combination chemotherapy for patients with relapsed/refractory peripheral T-cell lymphoma (PTCL).
Complete response (CR) rates and median survival times were significantly better among patients who received single agents than among those who received combination therapy.
Although researchers don’t know what is driving these differences in outcomes, they did find that outcomes were best among patients who received single-agent brentuximab vedotin (BV), and a disproportionate number of patients received BV.
The researchers also found that patients who received single-agent therapy were more likely to proceed to stem cell transplant.
Therefore, it’s still unclear if single-agent treatment is superior to combination therapy for relapsed/refractory PTCL, according to Robert Stuver, MD, of Beth Israel Deaconess Medical Center in Boston.
Dr. Stuver presented data from the COMPLETE (Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment) registry at the annual T-cell Lymphoma Forum.
The registry (NCT01110733) enrolled patients newly diagnosed with PTCL. Dr. Stuver presented results among patients who had relapsed after, or were refractory to, upfront therapy and went on to receive single-agent therapy or any combination regimen excluding those single agents. Outcome data were collected for 5 years or until death.
Patients and treatment
There were 26 patients in the combination treatment group — 10 with PTCL not otherwise specified (NOS), 6 with angioimmunoblastic T-cell lymphoma (AITL), 5 with natural killer T-cell lymphoma (NKTL), 3 with anaplastic large-cell lymphoma (ALCL), 1 with enteropathy-associated T-cell lymphoma (EATL), and 1 with hepatosplenic T-cell lymphoma (HSTCL).
Patients in the combination group received gemcitabine-based therapy (n = 10), ifosfamide-based therapy (n = 7), platinum-based therapy (n = 4), CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone)-like therapy (n = 1), DHAP (dexamethasone, high-dose cytarabine, and cisplatin; n = 1), and other combinations (n = 3).
There were 31 patients in the single-agent group – 13 with PTCL-NOS, 7 with ALCL, 5 with AITL, 2 with EATL, 2 with NKTL, and 2 with HSTCL.
These patients were treated with BV (n = 12), romidepsin (n = 8), pralatrexate (n = 5), alisertib (n = 3), bendamustine (n = 1), denileukin diftitox (n = 1), and lenalidomide (n = 1).
Response
The CR rates were significantly higher among patients who received single-agent treatment than among those who received combination therapy — 41.4% (12/31) and 19.2% (5/26), respectively (P = .02). The partial response rates were 17.2% (5/31) and 26.9% (7/26), respectively. Rates of stable disease were 3.4% (1/31) and 30.8% (8/26), respectively.
Complete responders in the single-agent arm were treated with BV (n = 7), romidepsin (n = 2), pralatrexate (n = 1), alisertib (n = 1), and bendamustine (n = 1). Four of the patients treated with BV had ALCL.
“We had an enrichment of patients treated with brentuximab,” Dr. Stuver said. “So the obvious question this begs is, ‘Are the favorable results that were seen for single agents over combination therapy solely due to patients treated with brentuximab?’ ”
To investigate, Dr. Stuver and his colleagues compared responses among patients who received BV with patients who received other single agents or combination therapies.
The CR rate was 58.3% (7/12) among BV recipients, 29.4% (5/17) among patients who received other single agents, and 19.2% (5/26) among patients who received combination therapy.
“The takeaway here is that, when you do divide the single-agent group into BV and other single agents, you’re seeing that BV is doing much better than every other group,” Dr. Stuver said. “And all the other single agents are doing somewhat similarly to the combination group, although there’s still a 10% difference, 29% versus 19%.”
Survival
The median progression-free survival (PFS) and overall survival (OS) were significantly better among patients who received single-agent therapy. The median PFS was 11.7 months in the single-agent group and 6.7 months in the combination group (P = .0197). The median OS was 38.9 months and 17.1 months, respectively (P = .0170).
A factor that may have affected survival is that patients were more likely to undergo stem cell transplant after single-agent therapy (25.8%, 8/31), compared with those who had received combination therapy (7.7%, 2/26).
Another factor that may have affected the survival differences is the enrichment of patients treated with BV.
The researchers found the median PFS was 11.9 months among BV recipients, 10.4 months among patients who received other single agents, and 6.7 months in the combination-therapy group. The median OS was 44.5 months, 19.1 months, and 17.1 months, respectively.
Dr. Stuver said these results suggest there is a role for single agents as first retreatment in the salvage setting. However, this analysis was limited by the small sample size and the enrichment of patients treated with BV.
Larger, randomized studies are needed to identify the “truly superior” treatment strategy for relapsed/refractory PTCL, Dr. Stuver said.
The COMPLETE registry is sponsored by Spectrum Pharmaceuticals. Dr. Stuver did not declare any conflicts of interest.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Key clinical point:
Major finding: The complete response rate was significantly higher among patients who received single-agent treatment than it was among those who received combination therapy – 41.4% and 19.2%, respectively (P = .02).
Study details: Analysis of 57 patients with relapsed/refractory PTCL in the COMPLETE registry.
Disclosures: The COMPLETE registry is sponsored by Spectrum Pharmaceuticals. Dr. Stuver did not declare any conflicts of interest.
Four-drug combo shows durable responses in relapsed/refractory lymphomas
LA JOLLA, CALIF. — Results of a phase 1 trial suggest a four-drug combination can produce durable responses in patients with relapsed or refractory T- and B-cell lymphomas.
Seven of 15 patients responded to treatment with romidepsin, gemcitabine, oxaliplatin, and dexamethasone, including six patients who achieved a complete response (CR).
The median duration of response was 8.5 months, and three patients had responses lasting more than 24 months.
Patients with angioimmunoblastic T-cell lymphoma (AITL) in particular responded well to the combination.
Neha Mehta-Shah, MD, of Washington University in St. Louis, and her colleagues presented these results in a poster at the annual T-cell Lymphoma Forum.
“[I]t was thought that the addition of histone deacetylase inhibitors to traditional platinum-based chemotherapies, which tend to cause DNA damage, would increase the response of platinum-based therapies,” Dr. Shah said.
With that in mind, she and her colleagues added romidepsin to gemcitabine, oxaliplatin, and dexamethasone and evaluated this combination in patients with relapsed/refractory lymphomas.
The trial (NCT02181218) enrolled 15 patients — 6 with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), 6 with diffuse large B-cell lymphoma (DLBCL), and 3 with AITL.
The patients’ median age was 66 (range, 55-83), and they had received a median of 2 (range, 1-4) prior therapies.
The researchers tested three dose levels of romidepsin — 8 mg/m2, 10 mg/m2, and 12 mg/m2 — given on day 2 of a 21-day cycle. The study originally included romidepsin on day 8 as well. However, the researchers discontinued the day 8 dose after patients developed grade 4 thrombocytopenia.
Patients also received gemcitabine at 1,000 mg/m2 (day 1), oxaliplatin at 100 mg/m2 (day 1), and dexamethasone at 20 mg (days 1-4). All patients received pegfilgrastim at 6 mg (day 3) as well.
The patients could receive up to eight cycles of treatment if they had stable disease or better and did not experience significant toxicity.
Safety
There was one dose-limiting toxicity (DLT) — pneumonia — at the 8 mg/m2 dose of romidepsin (given on days 2 and 8). There was one DLT — bleeding — at the 10 mg/m2 dose (day 2 only).
Two patients experienced DLTs — neutropenic fever and grade 4 thrombocytopenia — at the 12 mg/m2 dose (day 2 only).
Based on these events, 10 mg/m2 was considered the maximum-tolerated dose of romidepsin.
The most common adverse events (AEs) in this trial were thrombocytopenia (n = 13), electrolyte abnormalities (n = 12), liver function abnormalities (n = 10), anemia (n = 9), neutropenia (n = 8), fatigue (n = 7), nausea (n = 7), and creatinine increase (n = 5).
Grade 3/4 AEs included thrombocytopenia (n = 13), neutropenia (n = 5), anemia (n = 3), hyperglycemia (n = 2), hyperuricemia (n = 2), febrile neutropenia (n = 1), tumor lysis syndrome (n = 1), vomiting (n = 1), peripheral sensory neuropathy (n = 1), pneumonia (n = 1), sepsis (n = 1), bleeding (n = 1), and elevated troponin (n = 1).
Serious AEs requiring hospitalization included pneumonia (n = 1), nausea and vomiting (n = 1), tumor lysis syndrome (n = 1), and complications of disease progression (n = 4).
Efficacy
The overall response rate was 47% (7/15). CRs occurred in all three patients with AITL and two patients with DLBCL. One patient with PTCL-NOS had a CR, and one had a partial response.
The median duration of response was 8.5 months (range, 1.2-36.6 months). Four patients remain in CR — two with AITL, one with PTCL-NOS, and one with DLBCL.
Dr. Shah noted that the CRs in the AITL patients “have been quite prolonged.” One patient had a CR lasting 27 months, and another had a CR lasting 29 months.
Dr. Shah said these results are particularly exciting because patients discontinued study treatment after eight cycles or two cycles after they achieved a CR.
“[S]ome of these patients remained in remission for 2 years without any therapy thereafter, which is quite impressive in a population where the median survival — for patients with relapsed/refractory AITL — is thought to be 6-10 months,” Dr. Shah said.
She noted that this study is ongoing with an expansion cohort of patients with T-cell lymphomas.
This research was supported by Celgene. Dr. Shah reported relationships with Celgene, Kyowa Kirin, Bristol-Myers Squibb, Verastem, and Genentech.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. — Results of a phase 1 trial suggest a four-drug combination can produce durable responses in patients with relapsed or refractory T- and B-cell lymphomas.
Seven of 15 patients responded to treatment with romidepsin, gemcitabine, oxaliplatin, and dexamethasone, including six patients who achieved a complete response (CR).
The median duration of response was 8.5 months, and three patients had responses lasting more than 24 months.
Patients with angioimmunoblastic T-cell lymphoma (AITL) in particular responded well to the combination.
Neha Mehta-Shah, MD, of Washington University in St. Louis, and her colleagues presented these results in a poster at the annual T-cell Lymphoma Forum.
“[I]t was thought that the addition of histone deacetylase inhibitors to traditional platinum-based chemotherapies, which tend to cause DNA damage, would increase the response of platinum-based therapies,” Dr. Shah said.
With that in mind, she and her colleagues added romidepsin to gemcitabine, oxaliplatin, and dexamethasone and evaluated this combination in patients with relapsed/refractory lymphomas.
The trial (NCT02181218) enrolled 15 patients — 6 with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), 6 with diffuse large B-cell lymphoma (DLBCL), and 3 with AITL.
The patients’ median age was 66 (range, 55-83), and they had received a median of 2 (range, 1-4) prior therapies.
The researchers tested three dose levels of romidepsin — 8 mg/m2, 10 mg/m2, and 12 mg/m2 — given on day 2 of a 21-day cycle. The study originally included romidepsin on day 8 as well. However, the researchers discontinued the day 8 dose after patients developed grade 4 thrombocytopenia.
Patients also received gemcitabine at 1,000 mg/m2 (day 1), oxaliplatin at 100 mg/m2 (day 1), and dexamethasone at 20 mg (days 1-4). All patients received pegfilgrastim at 6 mg (day 3) as well.
The patients could receive up to eight cycles of treatment if they had stable disease or better and did not experience significant toxicity.
Safety
There was one dose-limiting toxicity (DLT) — pneumonia — at the 8 mg/m2 dose of romidepsin (given on days 2 and 8). There was one DLT — bleeding — at the 10 mg/m2 dose (day 2 only).
Two patients experienced DLTs — neutropenic fever and grade 4 thrombocytopenia — at the 12 mg/m2 dose (day 2 only).
Based on these events, 10 mg/m2 was considered the maximum-tolerated dose of romidepsin.
The most common adverse events (AEs) in this trial were thrombocytopenia (n = 13), electrolyte abnormalities (n = 12), liver function abnormalities (n = 10), anemia (n = 9), neutropenia (n = 8), fatigue (n = 7), nausea (n = 7), and creatinine increase (n = 5).
Grade 3/4 AEs included thrombocytopenia (n = 13), neutropenia (n = 5), anemia (n = 3), hyperglycemia (n = 2), hyperuricemia (n = 2), febrile neutropenia (n = 1), tumor lysis syndrome (n = 1), vomiting (n = 1), peripheral sensory neuropathy (n = 1), pneumonia (n = 1), sepsis (n = 1), bleeding (n = 1), and elevated troponin (n = 1).
Serious AEs requiring hospitalization included pneumonia (n = 1), nausea and vomiting (n = 1), tumor lysis syndrome (n = 1), and complications of disease progression (n = 4).
Efficacy
The overall response rate was 47% (7/15). CRs occurred in all three patients with AITL and two patients with DLBCL. One patient with PTCL-NOS had a CR, and one had a partial response.
The median duration of response was 8.5 months (range, 1.2-36.6 months). Four patients remain in CR — two with AITL, one with PTCL-NOS, and one with DLBCL.
Dr. Shah noted that the CRs in the AITL patients “have been quite prolonged.” One patient had a CR lasting 27 months, and another had a CR lasting 29 months.
Dr. Shah said these results are particularly exciting because patients discontinued study treatment after eight cycles or two cycles after they achieved a CR.
“[S]ome of these patients remained in remission for 2 years without any therapy thereafter, which is quite impressive in a population where the median survival — for patients with relapsed/refractory AITL — is thought to be 6-10 months,” Dr. Shah said.
She noted that this study is ongoing with an expansion cohort of patients with T-cell lymphomas.
This research was supported by Celgene. Dr. Shah reported relationships with Celgene, Kyowa Kirin, Bristol-Myers Squibb, Verastem, and Genentech.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. — Results of a phase 1 trial suggest a four-drug combination can produce durable responses in patients with relapsed or refractory T- and B-cell lymphomas.
Seven of 15 patients responded to treatment with romidepsin, gemcitabine, oxaliplatin, and dexamethasone, including six patients who achieved a complete response (CR).
The median duration of response was 8.5 months, and three patients had responses lasting more than 24 months.
Patients with angioimmunoblastic T-cell lymphoma (AITL) in particular responded well to the combination.
Neha Mehta-Shah, MD, of Washington University in St. Louis, and her colleagues presented these results in a poster at the annual T-cell Lymphoma Forum.
“[I]t was thought that the addition of histone deacetylase inhibitors to traditional platinum-based chemotherapies, which tend to cause DNA damage, would increase the response of platinum-based therapies,” Dr. Shah said.
With that in mind, she and her colleagues added romidepsin to gemcitabine, oxaliplatin, and dexamethasone and evaluated this combination in patients with relapsed/refractory lymphomas.
The trial (NCT02181218) enrolled 15 patients — 6 with peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), 6 with diffuse large B-cell lymphoma (DLBCL), and 3 with AITL.
The patients’ median age was 66 (range, 55-83), and they had received a median of 2 (range, 1-4) prior therapies.
The researchers tested three dose levels of romidepsin — 8 mg/m2, 10 mg/m2, and 12 mg/m2 — given on day 2 of a 21-day cycle. The study originally included romidepsin on day 8 as well. However, the researchers discontinued the day 8 dose after patients developed grade 4 thrombocytopenia.
Patients also received gemcitabine at 1,000 mg/m2 (day 1), oxaliplatin at 100 mg/m2 (day 1), and dexamethasone at 20 mg (days 1-4). All patients received pegfilgrastim at 6 mg (day 3) as well.
The patients could receive up to eight cycles of treatment if they had stable disease or better and did not experience significant toxicity.
Safety
There was one dose-limiting toxicity (DLT) — pneumonia — at the 8 mg/m2 dose of romidepsin (given on days 2 and 8). There was one DLT — bleeding — at the 10 mg/m2 dose (day 2 only).
Two patients experienced DLTs — neutropenic fever and grade 4 thrombocytopenia — at the 12 mg/m2 dose (day 2 only).
Based on these events, 10 mg/m2 was considered the maximum-tolerated dose of romidepsin.
The most common adverse events (AEs) in this trial were thrombocytopenia (n = 13), electrolyte abnormalities (n = 12), liver function abnormalities (n = 10), anemia (n = 9), neutropenia (n = 8), fatigue (n = 7), nausea (n = 7), and creatinine increase (n = 5).
Grade 3/4 AEs included thrombocytopenia (n = 13), neutropenia (n = 5), anemia (n = 3), hyperglycemia (n = 2), hyperuricemia (n = 2), febrile neutropenia (n = 1), tumor lysis syndrome (n = 1), vomiting (n = 1), peripheral sensory neuropathy (n = 1), pneumonia (n = 1), sepsis (n = 1), bleeding (n = 1), and elevated troponin (n = 1).
Serious AEs requiring hospitalization included pneumonia (n = 1), nausea and vomiting (n = 1), tumor lysis syndrome (n = 1), and complications of disease progression (n = 4).
Efficacy
The overall response rate was 47% (7/15). CRs occurred in all three patients with AITL and two patients with DLBCL. One patient with PTCL-NOS had a CR, and one had a partial response.
The median duration of response was 8.5 months (range, 1.2-36.6 months). Four patients remain in CR — two with AITL, one with PTCL-NOS, and one with DLBCL.
Dr. Shah noted that the CRs in the AITL patients “have been quite prolonged.” One patient had a CR lasting 27 months, and another had a CR lasting 29 months.
Dr. Shah said these results are particularly exciting because patients discontinued study treatment after eight cycles or two cycles after they achieved a CR.
“[S]ome of these patients remained in remission for 2 years without any therapy thereafter, which is quite impressive in a population where the median survival — for patients with relapsed/refractory AITL — is thought to be 6-10 months,” Dr. Shah said.
She noted that this study is ongoing with an expansion cohort of patients with T-cell lymphomas.
This research was supported by Celgene. Dr. Shah reported relationships with Celgene, Kyowa Kirin, Bristol-Myers Squibb, Verastem, and Genentech.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Key clinical point:
Major finding: Seven patients responded, and three patients had responses lasting more than 24 months.
Study details: Phase 1 trial of 15 patients.
Disclosures: This research was supported by Celgene. The presenter reported relationships with Celgene, Kyowa Kirin, Bristol-Myers Squibb, Verastem, and Genentech.
Long-term mogamulizumab appears safe, effective in CTCL
LA JOLLA, CALIF. — Prolonged exposure to mogamulizumab can improve responses without compromising safety in patients with cutaneous T-cell lymphoma (CTCL), according to a post hoc analysis of the MAVORIC trial.
Investigators found that exposure to mogamulizumab correlated with response. The highest response rate — 75.6% — was observed in patients exposed to the drug for at least 351 days, and the lowest — 1.9% — was observed in patients exposed to mogamulizumab for less than 72 days.
On the other hand, rates of adverse events (AEs) were similar regardless of how long patients were treated with mogamulizumab.
Youn H. Kim, MD, of Stanford Cancer Institute at Stanford (Calif.) University, and her colleagues presented these findings at the annual T-cell Lymphoma Forum.
The phase 3 MAVORIC trial (NCT01728805) included 372 adults with CTCL who had failed at least one systemic therapy. The patients were randomized to treatment with mogamulizumab or vorinostat.
Results from this comparison were previously reported at the 10th annual T-cell Lymphoma Forum.
At this year’s meeting, Dr. Kim and her colleagues reported results in 184 patients who were randomized to mogamulizumab — 105 of whom had mycosis fungoides (MF) and 79 of whom had Sézary syndrome (SS).
Patients were exposed to mogamulizumab for a mean of 275.2 days and a median of 170.0 days (range, 1-1,617 days).
The investigators divided patients into the following quartiles according to mogamulizumab exposure:
- Less than 72 days — 52 patients (28%)
- 72-170 days — 40 patients (22%)
- 171-351 days — 47 patients (26%)
- More than 351 days — 45 patients (24%).
Patients exposed to mogamulizumab for longer were more likely to have SS, stage III/IV disease, blood involvement, and a performance status of 0.
Dr. Kim said the SS patients “benefited a lot” from mogamulizumab and therefore remained on treatment longer.
Response
As expected, patients exposed to mogamulizumab for the longest period had the highest global response rates. Confirmed response rates according to drug exposure were as follows:
- Less than 72 days: 1.9% overall, 0% for SS, and 2.9% for MF
- 72-170 days: 10% overall, 18.8% for SS, and 4.2% for MF
- 171-351 days: 29.8% overall, 36.4% for SS, and 24% for MF
- More than 351 days: 75.6% overall, 83.3% for SS, and 66.7% for MF.
In addition, rates of complete response (CR) and partial response (PR) tended to increase with mogamulizumab exposure. Rates of CR, PR, and stable disease (SD) according to exposure time were as follows:
- Less than 72 days: 0% CR, 7.7% PR, and 38.5% SD
- 72-170 days: 2.5% CR, 20% PR, and 62.5% SD
- 171-351 days: 2.1% CR, 34% PR, and 57.4% SD
- More than 351 days: 6.7% CR, 71.1% PR, and 17.8% SD.
Safety
“The percentage of patients reporting adverse events was not different in the long-term treatment-exposure patients, compared to the short-term,” Dr. Kim said.
Percentages of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) according to mogamulizumab exposure were as follows:
- Less than 72 days: 26.6% TEAEs and 6.5% SAEs
- 72-170 days: 18.5% TEAEs and 3.3% SAEs
- 171-351 days: 23.4% TEAEs and 6.0% SAEs
- More than 351 days: 21.7% TEAEs and 4.3% SAEs.
“The majority of the grade 3 events occurred in the first two quartiles, not later, which is important to show,” Dr. Kim said.
Most grade 3 AEs occurred within 170 days of treatment initiation, and the median time to a grade 3 or higher AE was 109 days.
The most common treatment-related AEs in the longest exposure cohort were drug eruption (20.0%), thrombocytopenia (11.1%), stomatitis (8.9%), and anemia (8.9%).
Of all patients in this analysis, 45 experienced drug eruption, which was defined as a skin rash possibly, probably, or definitely related to the study drug.
Nine drug eruption events were grade 3, and the rest were grade 1 or 2. The median time to drug eruption was 107 days.
While drug eruption “didn’t show up early,” there is no cumulative risk with longer exposure to mogamulizumab, Dr. Kim said. Likewise, she said, autoimmune AEs were not dose-cumulative events.
There were two patients with definite autoimmune disease — a 65-year-old man with Miller Fisher syndrome (occurring 199 days after mogamulizumab initiation) and a 40-year-old woman with myositis (151 days) and myocarditis (310 days).
The investigators also identified three patients with possible autoimmune disease, including:
- Pneumonitis (310 days) in a 74-year-old woman
- Polymyalgia rheumatica (209 days) and myopathy (not available) in an 84-year-old man
- Hepatitis (144 days), pneumonitis (about 174 days), and polymyositis (about 174 days) in a 73-year-old man.
Dr. Kim and her colleagues said these data suggest prolonged treatment with mogamulizumab is not associated with an increased safety risk in patients with MF or SS. And the manageable safety profile of mogamulizumab meant that patients who derived a clinical benefit could remain on the drug for an extended period of time.
The MAVORIC trial was sponsored by Kyowa Hakko Kirin Pharma. Dr. Kim reported relationships with Merck, Portola Pharmaceuticals, Soligenix, Takeda, TetraLogic Pharmaceuticals, Kyowa Kirin, Seattle Genetics, Medivir, Neumedicines, Eisai, Innate Pharma, Galderma, Miragen Therapeutics, Forty Seven, and Horizon Pharma. Her coinvestigators reported relationships with several companies.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. — Prolonged exposure to mogamulizumab can improve responses without compromising safety in patients with cutaneous T-cell lymphoma (CTCL), according to a post hoc analysis of the MAVORIC trial.
Investigators found that exposure to mogamulizumab correlated with response. The highest response rate — 75.6% — was observed in patients exposed to the drug for at least 351 days, and the lowest — 1.9% — was observed in patients exposed to mogamulizumab for less than 72 days.
On the other hand, rates of adverse events (AEs) were similar regardless of how long patients were treated with mogamulizumab.
Youn H. Kim, MD, of Stanford Cancer Institute at Stanford (Calif.) University, and her colleagues presented these findings at the annual T-cell Lymphoma Forum.
The phase 3 MAVORIC trial (NCT01728805) included 372 adults with CTCL who had failed at least one systemic therapy. The patients were randomized to treatment with mogamulizumab or vorinostat.
Results from this comparison were previously reported at the 10th annual T-cell Lymphoma Forum.
At this year’s meeting, Dr. Kim and her colleagues reported results in 184 patients who were randomized to mogamulizumab — 105 of whom had mycosis fungoides (MF) and 79 of whom had Sézary syndrome (SS).
Patients were exposed to mogamulizumab for a mean of 275.2 days and a median of 170.0 days (range, 1-1,617 days).
The investigators divided patients into the following quartiles according to mogamulizumab exposure:
- Less than 72 days — 52 patients (28%)
- 72-170 days — 40 patients (22%)
- 171-351 days — 47 patients (26%)
- More than 351 days — 45 patients (24%).
Patients exposed to mogamulizumab for longer were more likely to have SS, stage III/IV disease, blood involvement, and a performance status of 0.
Dr. Kim said the SS patients “benefited a lot” from mogamulizumab and therefore remained on treatment longer.
Response
As expected, patients exposed to mogamulizumab for the longest period had the highest global response rates. Confirmed response rates according to drug exposure were as follows:
- Less than 72 days: 1.9% overall, 0% for SS, and 2.9% for MF
- 72-170 days: 10% overall, 18.8% for SS, and 4.2% for MF
- 171-351 days: 29.8% overall, 36.4% for SS, and 24% for MF
- More than 351 days: 75.6% overall, 83.3% for SS, and 66.7% for MF.
In addition, rates of complete response (CR) and partial response (PR) tended to increase with mogamulizumab exposure. Rates of CR, PR, and stable disease (SD) according to exposure time were as follows:
- Less than 72 days: 0% CR, 7.7% PR, and 38.5% SD
- 72-170 days: 2.5% CR, 20% PR, and 62.5% SD
- 171-351 days: 2.1% CR, 34% PR, and 57.4% SD
- More than 351 days: 6.7% CR, 71.1% PR, and 17.8% SD.
Safety
“The percentage of patients reporting adverse events was not different in the long-term treatment-exposure patients, compared to the short-term,” Dr. Kim said.
Percentages of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) according to mogamulizumab exposure were as follows:
- Less than 72 days: 26.6% TEAEs and 6.5% SAEs
- 72-170 days: 18.5% TEAEs and 3.3% SAEs
- 171-351 days: 23.4% TEAEs and 6.0% SAEs
- More than 351 days: 21.7% TEAEs and 4.3% SAEs.
“The majority of the grade 3 events occurred in the first two quartiles, not later, which is important to show,” Dr. Kim said.
Most grade 3 AEs occurred within 170 days of treatment initiation, and the median time to a grade 3 or higher AE was 109 days.
The most common treatment-related AEs in the longest exposure cohort were drug eruption (20.0%), thrombocytopenia (11.1%), stomatitis (8.9%), and anemia (8.9%).
Of all patients in this analysis, 45 experienced drug eruption, which was defined as a skin rash possibly, probably, or definitely related to the study drug.
Nine drug eruption events were grade 3, and the rest were grade 1 or 2. The median time to drug eruption was 107 days.
While drug eruption “didn’t show up early,” there is no cumulative risk with longer exposure to mogamulizumab, Dr. Kim said. Likewise, she said, autoimmune AEs were not dose-cumulative events.
There were two patients with definite autoimmune disease — a 65-year-old man with Miller Fisher syndrome (occurring 199 days after mogamulizumab initiation) and a 40-year-old woman with myositis (151 days) and myocarditis (310 days).
The investigators also identified three patients with possible autoimmune disease, including:
- Pneumonitis (310 days) in a 74-year-old woman
- Polymyalgia rheumatica (209 days) and myopathy (not available) in an 84-year-old man
- Hepatitis (144 days), pneumonitis (about 174 days), and polymyositis (about 174 days) in a 73-year-old man.
Dr. Kim and her colleagues said these data suggest prolonged treatment with mogamulizumab is not associated with an increased safety risk in patients with MF or SS. And the manageable safety profile of mogamulizumab meant that patients who derived a clinical benefit could remain on the drug for an extended period of time.
The MAVORIC trial was sponsored by Kyowa Hakko Kirin Pharma. Dr. Kim reported relationships with Merck, Portola Pharmaceuticals, Soligenix, Takeda, TetraLogic Pharmaceuticals, Kyowa Kirin, Seattle Genetics, Medivir, Neumedicines, Eisai, Innate Pharma, Galderma, Miragen Therapeutics, Forty Seven, and Horizon Pharma. Her coinvestigators reported relationships with several companies.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. — Prolonged exposure to mogamulizumab can improve responses without compromising safety in patients with cutaneous T-cell lymphoma (CTCL), according to a post hoc analysis of the MAVORIC trial.
Investigators found that exposure to mogamulizumab correlated with response. The highest response rate — 75.6% — was observed in patients exposed to the drug for at least 351 days, and the lowest — 1.9% — was observed in patients exposed to mogamulizumab for less than 72 days.
On the other hand, rates of adverse events (AEs) were similar regardless of how long patients were treated with mogamulizumab.
Youn H. Kim, MD, of Stanford Cancer Institute at Stanford (Calif.) University, and her colleagues presented these findings at the annual T-cell Lymphoma Forum.
The phase 3 MAVORIC trial (NCT01728805) included 372 adults with CTCL who had failed at least one systemic therapy. The patients were randomized to treatment with mogamulizumab or vorinostat.
Results from this comparison were previously reported at the 10th annual T-cell Lymphoma Forum.
At this year’s meeting, Dr. Kim and her colleagues reported results in 184 patients who were randomized to mogamulizumab — 105 of whom had mycosis fungoides (MF) and 79 of whom had Sézary syndrome (SS).
Patients were exposed to mogamulizumab for a mean of 275.2 days and a median of 170.0 days (range, 1-1,617 days).
The investigators divided patients into the following quartiles according to mogamulizumab exposure:
- Less than 72 days — 52 patients (28%)
- 72-170 days — 40 patients (22%)
- 171-351 days — 47 patients (26%)
- More than 351 days — 45 patients (24%).
Patients exposed to mogamulizumab for longer were more likely to have SS, stage III/IV disease, blood involvement, and a performance status of 0.
Dr. Kim said the SS patients “benefited a lot” from mogamulizumab and therefore remained on treatment longer.
Response
As expected, patients exposed to mogamulizumab for the longest period had the highest global response rates. Confirmed response rates according to drug exposure were as follows:
- Less than 72 days: 1.9% overall, 0% for SS, and 2.9% for MF
- 72-170 days: 10% overall, 18.8% for SS, and 4.2% for MF
- 171-351 days: 29.8% overall, 36.4% for SS, and 24% for MF
- More than 351 days: 75.6% overall, 83.3% for SS, and 66.7% for MF.
In addition, rates of complete response (CR) and partial response (PR) tended to increase with mogamulizumab exposure. Rates of CR, PR, and stable disease (SD) according to exposure time were as follows:
- Less than 72 days: 0% CR, 7.7% PR, and 38.5% SD
- 72-170 days: 2.5% CR, 20% PR, and 62.5% SD
- 171-351 days: 2.1% CR, 34% PR, and 57.4% SD
- More than 351 days: 6.7% CR, 71.1% PR, and 17.8% SD.
Safety
“The percentage of patients reporting adverse events was not different in the long-term treatment-exposure patients, compared to the short-term,” Dr. Kim said.
Percentages of treatment-emergent AEs (TEAEs) and serious AEs (SAEs) according to mogamulizumab exposure were as follows:
- Less than 72 days: 26.6% TEAEs and 6.5% SAEs
- 72-170 days: 18.5% TEAEs and 3.3% SAEs
- 171-351 days: 23.4% TEAEs and 6.0% SAEs
- More than 351 days: 21.7% TEAEs and 4.3% SAEs.
“The majority of the grade 3 events occurred in the first two quartiles, not later, which is important to show,” Dr. Kim said.
Most grade 3 AEs occurred within 170 days of treatment initiation, and the median time to a grade 3 or higher AE was 109 days.
The most common treatment-related AEs in the longest exposure cohort were drug eruption (20.0%), thrombocytopenia (11.1%), stomatitis (8.9%), and anemia (8.9%).
Of all patients in this analysis, 45 experienced drug eruption, which was defined as a skin rash possibly, probably, or definitely related to the study drug.
Nine drug eruption events were grade 3, and the rest were grade 1 or 2. The median time to drug eruption was 107 days.
While drug eruption “didn’t show up early,” there is no cumulative risk with longer exposure to mogamulizumab, Dr. Kim said. Likewise, she said, autoimmune AEs were not dose-cumulative events.
There were two patients with definite autoimmune disease — a 65-year-old man with Miller Fisher syndrome (occurring 199 days after mogamulizumab initiation) and a 40-year-old woman with myositis (151 days) and myocarditis (310 days).
The investigators also identified three patients with possible autoimmune disease, including:
- Pneumonitis (310 days) in a 74-year-old woman
- Polymyalgia rheumatica (209 days) and myopathy (not available) in an 84-year-old man
- Hepatitis (144 days), pneumonitis (about 174 days), and polymyositis (about 174 days) in a 73-year-old man.
Dr. Kim and her colleagues said these data suggest prolonged treatment with mogamulizumab is not associated with an increased safety risk in patients with MF or SS. And the manageable safety profile of mogamulizumab meant that patients who derived a clinical benefit could remain on the drug for an extended period of time.
The MAVORIC trial was sponsored by Kyowa Hakko Kirin Pharma. Dr. Kim reported relationships with Merck, Portola Pharmaceuticals, Soligenix, Takeda, TetraLogic Pharmaceuticals, Kyowa Kirin, Seattle Genetics, Medivir, Neumedicines, Eisai, Innate Pharma, Galderma, Miragen Therapeutics, Forty Seven, and Horizon Pharma. Her coinvestigators reported relationships with several companies.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Key clinical point:
Major finding: The highest response rate – 75.6% – was observed in patients exposed to mogamulizumab for at least 351 days.
Study details: A post hoc analysis of the MAVORIC trial, including 184 patients treated with mogamulizumab.
Disclosures: The MAVORIC trial was sponsored by Kyowa Hakko Kirin Pharma. Investigators disclosed relationships with several companies.
Chidamide may be more effective in PTCL than previously thought
LA JOLLA, CALIF. – Real-world data suggest chidamide may be more effective against relapsed or refractory peripheral T-cell lymphoma (PTCL) than a pivotal study indicated.
Single-agent chidamide produced an overall response rate of 47.0% in a real-world study of more than 1,000 patients, compared with the 28.0% overall response rate that was observed in the phase 2 study of chidamide (Ann Oncol. 2015 Aug;26[8]:1766-71).
Yuqin Song, MD, PhD, of Peking University Cancer Hospital and Institute in Beijing, China, presented data from the real-world study at the annual T-cell Lymphoma Forum.
Dr. Song said this study is the largest cohort of real-world patients with relapsed or refractory PTCL. She and her colleagues analyzed data on 1,064 patients treated at 216 sites across China between February 2015 and December 2017.
The patients had a median age of 54 years, 63.9% were male, and 88.1% had stage III-IV disease.
Disease subtypes included PTCL not otherwise specified (NOS, 38.0%), angioimmunoblastic T-cell lymphoma (AITL, 29.1%), extranodal natural killer T-cell lymphoma (ENKTL, 13.4%), anaplastic large-cell lymphoma (ALCL, 9.1%), and others (10.3%), including cutaneous T-cell lymphoma (CTCL).
Fifty-two percent of patients (n = 553) received chidamide as a single agent, and 48% (n = 511) received the drug with other agents. The most common treatment regimens combined with chidamide were the following
- Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, 20.7%).
- Gemcitabine, dexamethasone, and cisplatin (GDP, 11.8%).
- Etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH, 9.8%).
- Patients with ENKTL received chidamide with L-asparaginase (35.4%) or without it (64.5%).
The median follow-up was 4.9 months (range, 0-36.2 months). Across disease subtypes, the overall response rate was 47.0% with single-agent chidamide and 65.4% when chidamide was given in combination with other agents (P less than .01).
The median overall survival was 400 days for all patients, 342 days for patients treated with chidamide alone, and 457 days for patients who received combination therapy. The 1-year overall survival rates were 52%, 48%, and 56%, respectively.
Dr. Song said these data verify the efficacy of chidamide as a single agent and suggest chidamide might lead to improved survival in refractory or relapsed PTCLs.
Chidamide was generally well tolerated in this study, Dr. Song said. There were no unexpected adverse events (AEs) and most were grade 1 or 2.
The most common AEs (of any grade) observed with single-agent chidamide were neutropenia (42.9%), thrombocytopenia (40.5%), fatigue (38.3%), anemia (31.6%), and nausea/vomiting (21.0%).
The most common AEs observed with chidamide in combination were neutropenia (61.4%), thrombocytopenia (58.5%), fatigue (56.2%), anemia (54.2%), nausea/vomiting (30.7%), and fever (22.1%).
This study was supported by the Union for China Lymphoma Investigators and the Chinese Society of Clinical Oncology. Dr. Song did not disclose any conflicts of interest.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – Real-world data suggest chidamide may be more effective against relapsed or refractory peripheral T-cell lymphoma (PTCL) than a pivotal study indicated.
Single-agent chidamide produced an overall response rate of 47.0% in a real-world study of more than 1,000 patients, compared with the 28.0% overall response rate that was observed in the phase 2 study of chidamide (Ann Oncol. 2015 Aug;26[8]:1766-71).
Yuqin Song, MD, PhD, of Peking University Cancer Hospital and Institute in Beijing, China, presented data from the real-world study at the annual T-cell Lymphoma Forum.
Dr. Song said this study is the largest cohort of real-world patients with relapsed or refractory PTCL. She and her colleagues analyzed data on 1,064 patients treated at 216 sites across China between February 2015 and December 2017.
The patients had a median age of 54 years, 63.9% were male, and 88.1% had stage III-IV disease.
Disease subtypes included PTCL not otherwise specified (NOS, 38.0%), angioimmunoblastic T-cell lymphoma (AITL, 29.1%), extranodal natural killer T-cell lymphoma (ENKTL, 13.4%), anaplastic large-cell lymphoma (ALCL, 9.1%), and others (10.3%), including cutaneous T-cell lymphoma (CTCL).
Fifty-two percent of patients (n = 553) received chidamide as a single agent, and 48% (n = 511) received the drug with other agents. The most common treatment regimens combined with chidamide were the following
- Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, 20.7%).
- Gemcitabine, dexamethasone, and cisplatin (GDP, 11.8%).
- Etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH, 9.8%).
- Patients with ENKTL received chidamide with L-asparaginase (35.4%) or without it (64.5%).
The median follow-up was 4.9 months (range, 0-36.2 months). Across disease subtypes, the overall response rate was 47.0% with single-agent chidamide and 65.4% when chidamide was given in combination with other agents (P less than .01).
The median overall survival was 400 days for all patients, 342 days for patients treated with chidamide alone, and 457 days for patients who received combination therapy. The 1-year overall survival rates were 52%, 48%, and 56%, respectively.
Dr. Song said these data verify the efficacy of chidamide as a single agent and suggest chidamide might lead to improved survival in refractory or relapsed PTCLs.
Chidamide was generally well tolerated in this study, Dr. Song said. There were no unexpected adverse events (AEs) and most were grade 1 or 2.
The most common AEs (of any grade) observed with single-agent chidamide were neutropenia (42.9%), thrombocytopenia (40.5%), fatigue (38.3%), anemia (31.6%), and nausea/vomiting (21.0%).
The most common AEs observed with chidamide in combination were neutropenia (61.4%), thrombocytopenia (58.5%), fatigue (56.2%), anemia (54.2%), nausea/vomiting (30.7%), and fever (22.1%).
This study was supported by the Union for China Lymphoma Investigators and the Chinese Society of Clinical Oncology. Dr. Song did not disclose any conflicts of interest.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – Real-world data suggest chidamide may be more effective against relapsed or refractory peripheral T-cell lymphoma (PTCL) than a pivotal study indicated.
Single-agent chidamide produced an overall response rate of 47.0% in a real-world study of more than 1,000 patients, compared with the 28.0% overall response rate that was observed in the phase 2 study of chidamide (Ann Oncol. 2015 Aug;26[8]:1766-71).
Yuqin Song, MD, PhD, of Peking University Cancer Hospital and Institute in Beijing, China, presented data from the real-world study at the annual T-cell Lymphoma Forum.
Dr. Song said this study is the largest cohort of real-world patients with relapsed or refractory PTCL. She and her colleagues analyzed data on 1,064 patients treated at 216 sites across China between February 2015 and December 2017.
The patients had a median age of 54 years, 63.9% were male, and 88.1% had stage III-IV disease.
Disease subtypes included PTCL not otherwise specified (NOS, 38.0%), angioimmunoblastic T-cell lymphoma (AITL, 29.1%), extranodal natural killer T-cell lymphoma (ENKTL, 13.4%), anaplastic large-cell lymphoma (ALCL, 9.1%), and others (10.3%), including cutaneous T-cell lymphoma (CTCL).
Fifty-two percent of patients (n = 553) received chidamide as a single agent, and 48% (n = 511) received the drug with other agents. The most common treatment regimens combined with chidamide were the following
- Cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP, 20.7%).
- Gemcitabine, dexamethasone, and cisplatin (GDP, 11.8%).
- Etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin (EPOCH, 9.8%).
- Patients with ENKTL received chidamide with L-asparaginase (35.4%) or without it (64.5%).
The median follow-up was 4.9 months (range, 0-36.2 months). Across disease subtypes, the overall response rate was 47.0% with single-agent chidamide and 65.4% when chidamide was given in combination with other agents (P less than .01).
The median overall survival was 400 days for all patients, 342 days for patients treated with chidamide alone, and 457 days for patients who received combination therapy. The 1-year overall survival rates were 52%, 48%, and 56%, respectively.
Dr. Song said these data verify the efficacy of chidamide as a single agent and suggest chidamide might lead to improved survival in refractory or relapsed PTCLs.
Chidamide was generally well tolerated in this study, Dr. Song said. There were no unexpected adverse events (AEs) and most were grade 1 or 2.
The most common AEs (of any grade) observed with single-agent chidamide were neutropenia (42.9%), thrombocytopenia (40.5%), fatigue (38.3%), anemia (31.6%), and nausea/vomiting (21.0%).
The most common AEs observed with chidamide in combination were neutropenia (61.4%), thrombocytopenia (58.5%), fatigue (56.2%), anemia (54.2%), nausea/vomiting (30.7%), and fever (22.1%).
This study was supported by the Union for China Lymphoma Investigators and the Chinese Society of Clinical Oncology. Dr. Song did not disclose any conflicts of interest.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Key clinical point:
Major finding: Single-agent chidamide had an overall response rate of 47.0% among relapsed/refractory PTCL patients, compared with 65.4% when used in combination with other agents (P less than .01).
Study details: A real-world cohort of 1,064 relapsed/refractory PTCL patients treated at 216 sites across China between February 2015 and December 2017.
Disclosures: The study was supported by the Union for China Lymphoma Investigators and the Chinese Society of Clinical Oncology. Dr. Song did not disclose any conflicts of interest.
Epigenetics is a hot topic at TCLF 2019
LA JOLLA, CALIF. –
In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.
Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.
Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.
And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. –
In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.
Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.
Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.
And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. –
In a video interview, meeting cochair Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, discussed a few presentations that addressed epigenetics in T-cell lymphomas.
Stephen Baylin, MD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore, gave the meeting’s keynote address, which focused on the idea that epigenetic therapy can enhance immune checkpoint therapy.
Susan Bates, MD, of Columbia University Medical Center, presented data that suggest romidepsin and other histone deacetylase inhibitors fight cutaneous T-cell lymphoma via epigenetic effects on gene expression, as well as DNA damage.
And Enrica Marchi, MD, PhD, of Columbia University Medical Center, discussed the use of epigenetic-based combination therapies to improve responses in T-cell lymphomas.
The T-cell Lymphoma Forum is organized by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Registry data favor CHOEP regimen for PTCL
LA JOLLA, CALIF. – Data from the Czech National Lymphoma Registry (NiHiL) suggest the CHOEP regimen (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) prolongs survival in newly diagnosed patients with peripheral T-cell lymphoma (PTCL), but consolidation with autologous stem cell transplant (ASCT) does not.
“We failed to show that there is a real benefit for the patient to undergo autologous stem cell consolidation, so, nowadays, in the majority of the centers in our group, CHOEP is the chemotherapy of choice, and the patients are not consolidated,” said Marek Trneny, MD, of Charles University General Hospital in Prague.
Dr. Trneny presented results from NiHiL on behalf of the Czech Lymphoma Study Group at the annual T-cell Lymphoma Forum.
The NiHiL project is a prospective, observational study (NCT03199066) of patients newly diagnosed with non-Hodgkin lymphoma in the Czech Republic.
Dr. Trneny presented data on 838 PTCL patients who were diagnosed between 1999 and 2018, 462 of whom were included in a survival analysis (1999-2016).
The 462 patients had a median age of 61 years and more than half were men.
Patients had PTCL not otherwise specified (NOS, 43.9%), Anaplastic lymphoma kinase (ALK)–negative Anaplastic large-cell lymphoma (ALCL, 20.8%), ALK-positive ALCL (7.6%), unclassified ALCL (0.9%), angioimmunoblastic T-cell lymphoma (AITL, 10.6%), and other subtypes (16.2%).
Most patients (79.1%) had tumors measuring less than 7.5 cm, about half of patients (52.3%) had B symptoms, most (70.5%) had a performance status of 0-1, and most (68.5%) had stage III-IV disease. Half of patients were low or low/intermediate risk according to the International Prognostic Index.
For the entire cohort, the median progression-free survival (PFS) was 1.15 years, and the 5-year PFS rate was 34.2%. The median overall survival (OS) was 2.83 years, and the 5-year OS rate was 43.3%.
There was no significant difference in PFS or OS for patients diagnosed from 1999 to 2007 and those diagnosed from 2008 to 2016. The median PFS was 1.05 years and 1.23 years, respectively (P= .4487), and the median OS was 2.15 years and 3.39 years, respectively (P = .176).
Patients with ALK-positive ALCL had superior PFS and OS when compared to patients with the other disease subtypes (P = .0002 for PFS and P = .0009 for OS).
Treatment comparison
When Dr. Trneny and his colleagues compared the 223 patients who received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and the 65 patients who received CHOEP, the researchers found that patients who received CHOEP had superior PFS and OS.
In the CHOP group, the median PFS was 1.18 years and the 5-year PFS rate was 34.2%. In the CHOEP group, the median PFS was 3.67 years and the 5-year PFS rate was 49.0% (hazard ratio, 0.6781; P = .0373).
In the CHOP group, the median OS was 3.74 years and the 5-year OS was 45.5%. In the CHOEP group, the median OS was 7.46 years and the 5-year OS was 56.4% (HR, 0.6475; P = .0381).
Dr. Trneny noted that patients who received CHOP were significantly younger (P less than .0001), more likely to have AITL or ALK-positive ALCL (P = .0152), and more likely to have a performance status of 2-4 (P = .0385).
Dr. Trneny and his colleagues also compared survival in 56 ASCT recipients and 189 patients who received chemotherapy alone (either CHOP or CHOEP).
Patients who underwent ASCT were significantly younger (P less than .0001) and more likely to have stage III or IV disease (P = .0345).
However, the researchers found no significant survival differences between patients who underwent ASCT and those who did not.
ASCT recipients had a median PFS of 7.50 years and a 5-year PFS rate of 56.0%, while patients who received chemotherapy alone had a median PFS of 4.69 years and a 5-year PFS rate of 47.3% (P = .6537).
In ASCT recipients, the median OS was not reached, and the 5-year OS rate was 63.3%. Among patients who received chemotherapy alone, the median OS was 6.78 years, and the 5-year OS was 63.0% (P = .6201).
“For those patients who are eligible for a CHOP-like regimen, CHOEP gives a higher chance for longer progression-free survival and overall survival, at least in our ... analysis,” Dr. Trneny said. “Autologous stem cell transplant, on the other hand, doesn’t seem to prolong PFS or overall survival.”
This research is sponsored by the Czech Lymphoma Study Group. Dr. Trneny did not disclose any conflicts of interest.
The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – Data from the Czech National Lymphoma Registry (NiHiL) suggest the CHOEP regimen (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) prolongs survival in newly diagnosed patients with peripheral T-cell lymphoma (PTCL), but consolidation with autologous stem cell transplant (ASCT) does not.
“We failed to show that there is a real benefit for the patient to undergo autologous stem cell consolidation, so, nowadays, in the majority of the centers in our group, CHOEP is the chemotherapy of choice, and the patients are not consolidated,” said Marek Trneny, MD, of Charles University General Hospital in Prague.
Dr. Trneny presented results from NiHiL on behalf of the Czech Lymphoma Study Group at the annual T-cell Lymphoma Forum.
The NiHiL project is a prospective, observational study (NCT03199066) of patients newly diagnosed with non-Hodgkin lymphoma in the Czech Republic.
Dr. Trneny presented data on 838 PTCL patients who were diagnosed between 1999 and 2018, 462 of whom were included in a survival analysis (1999-2016).
The 462 patients had a median age of 61 years and more than half were men.
Patients had PTCL not otherwise specified (NOS, 43.9%), Anaplastic lymphoma kinase (ALK)–negative Anaplastic large-cell lymphoma (ALCL, 20.8%), ALK-positive ALCL (7.6%), unclassified ALCL (0.9%), angioimmunoblastic T-cell lymphoma (AITL, 10.6%), and other subtypes (16.2%).
Most patients (79.1%) had tumors measuring less than 7.5 cm, about half of patients (52.3%) had B symptoms, most (70.5%) had a performance status of 0-1, and most (68.5%) had stage III-IV disease. Half of patients were low or low/intermediate risk according to the International Prognostic Index.
For the entire cohort, the median progression-free survival (PFS) was 1.15 years, and the 5-year PFS rate was 34.2%. The median overall survival (OS) was 2.83 years, and the 5-year OS rate was 43.3%.
There was no significant difference in PFS or OS for patients diagnosed from 1999 to 2007 and those diagnosed from 2008 to 2016. The median PFS was 1.05 years and 1.23 years, respectively (P= .4487), and the median OS was 2.15 years and 3.39 years, respectively (P = .176).
Patients with ALK-positive ALCL had superior PFS and OS when compared to patients with the other disease subtypes (P = .0002 for PFS and P = .0009 for OS).
Treatment comparison
When Dr. Trneny and his colleagues compared the 223 patients who received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and the 65 patients who received CHOEP, the researchers found that patients who received CHOEP had superior PFS and OS.
In the CHOP group, the median PFS was 1.18 years and the 5-year PFS rate was 34.2%. In the CHOEP group, the median PFS was 3.67 years and the 5-year PFS rate was 49.0% (hazard ratio, 0.6781; P = .0373).
In the CHOP group, the median OS was 3.74 years and the 5-year OS was 45.5%. In the CHOEP group, the median OS was 7.46 years and the 5-year OS was 56.4% (HR, 0.6475; P = .0381).
Dr. Trneny noted that patients who received CHOP were significantly younger (P less than .0001), more likely to have AITL or ALK-positive ALCL (P = .0152), and more likely to have a performance status of 2-4 (P = .0385).
Dr. Trneny and his colleagues also compared survival in 56 ASCT recipients and 189 patients who received chemotherapy alone (either CHOP or CHOEP).
Patients who underwent ASCT were significantly younger (P less than .0001) and more likely to have stage III or IV disease (P = .0345).
However, the researchers found no significant survival differences between patients who underwent ASCT and those who did not.
ASCT recipients had a median PFS of 7.50 years and a 5-year PFS rate of 56.0%, while patients who received chemotherapy alone had a median PFS of 4.69 years and a 5-year PFS rate of 47.3% (P = .6537).
In ASCT recipients, the median OS was not reached, and the 5-year OS rate was 63.3%. Among patients who received chemotherapy alone, the median OS was 6.78 years, and the 5-year OS was 63.0% (P = .6201).
“For those patients who are eligible for a CHOP-like regimen, CHOEP gives a higher chance for longer progression-free survival and overall survival, at least in our ... analysis,” Dr. Trneny said. “Autologous stem cell transplant, on the other hand, doesn’t seem to prolong PFS or overall survival.”
This research is sponsored by the Czech Lymphoma Study Group. Dr. Trneny did not disclose any conflicts of interest.
The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
LA JOLLA, CALIF. – Data from the Czech National Lymphoma Registry (NiHiL) suggest the CHOEP regimen (cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone) prolongs survival in newly diagnosed patients with peripheral T-cell lymphoma (PTCL), but consolidation with autologous stem cell transplant (ASCT) does not.
“We failed to show that there is a real benefit for the patient to undergo autologous stem cell consolidation, so, nowadays, in the majority of the centers in our group, CHOEP is the chemotherapy of choice, and the patients are not consolidated,” said Marek Trneny, MD, of Charles University General Hospital in Prague.
Dr. Trneny presented results from NiHiL on behalf of the Czech Lymphoma Study Group at the annual T-cell Lymphoma Forum.
The NiHiL project is a prospective, observational study (NCT03199066) of patients newly diagnosed with non-Hodgkin lymphoma in the Czech Republic.
Dr. Trneny presented data on 838 PTCL patients who were diagnosed between 1999 and 2018, 462 of whom were included in a survival analysis (1999-2016).
The 462 patients had a median age of 61 years and more than half were men.
Patients had PTCL not otherwise specified (NOS, 43.9%), Anaplastic lymphoma kinase (ALK)–negative Anaplastic large-cell lymphoma (ALCL, 20.8%), ALK-positive ALCL (7.6%), unclassified ALCL (0.9%), angioimmunoblastic T-cell lymphoma (AITL, 10.6%), and other subtypes (16.2%).
Most patients (79.1%) had tumors measuring less than 7.5 cm, about half of patients (52.3%) had B symptoms, most (70.5%) had a performance status of 0-1, and most (68.5%) had stage III-IV disease. Half of patients were low or low/intermediate risk according to the International Prognostic Index.
For the entire cohort, the median progression-free survival (PFS) was 1.15 years, and the 5-year PFS rate was 34.2%. The median overall survival (OS) was 2.83 years, and the 5-year OS rate was 43.3%.
There was no significant difference in PFS or OS for patients diagnosed from 1999 to 2007 and those diagnosed from 2008 to 2016. The median PFS was 1.05 years and 1.23 years, respectively (P= .4487), and the median OS was 2.15 years and 3.39 years, respectively (P = .176).
Patients with ALK-positive ALCL had superior PFS and OS when compared to patients with the other disease subtypes (P = .0002 for PFS and P = .0009 for OS).
Treatment comparison
When Dr. Trneny and his colleagues compared the 223 patients who received CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone) and the 65 patients who received CHOEP, the researchers found that patients who received CHOEP had superior PFS and OS.
In the CHOP group, the median PFS was 1.18 years and the 5-year PFS rate was 34.2%. In the CHOEP group, the median PFS was 3.67 years and the 5-year PFS rate was 49.0% (hazard ratio, 0.6781; P = .0373).
In the CHOP group, the median OS was 3.74 years and the 5-year OS was 45.5%. In the CHOEP group, the median OS was 7.46 years and the 5-year OS was 56.4% (HR, 0.6475; P = .0381).
Dr. Trneny noted that patients who received CHOP were significantly younger (P less than .0001), more likely to have AITL or ALK-positive ALCL (P = .0152), and more likely to have a performance status of 2-4 (P = .0385).
Dr. Trneny and his colleagues also compared survival in 56 ASCT recipients and 189 patients who received chemotherapy alone (either CHOP or CHOEP).
Patients who underwent ASCT were significantly younger (P less than .0001) and more likely to have stage III or IV disease (P = .0345).
However, the researchers found no significant survival differences between patients who underwent ASCT and those who did not.
ASCT recipients had a median PFS of 7.50 years and a 5-year PFS rate of 56.0%, while patients who received chemotherapy alone had a median PFS of 4.69 years and a 5-year PFS rate of 47.3% (P = .6537).
In ASCT recipients, the median OS was not reached, and the 5-year OS rate was 63.3%. Among patients who received chemotherapy alone, the median OS was 6.78 years, and the 5-year OS was 63.0% (P = .6201).
“For those patients who are eligible for a CHOP-like regimen, CHOEP gives a higher chance for longer progression-free survival and overall survival, at least in our ... analysis,” Dr. Trneny said. “Autologous stem cell transplant, on the other hand, doesn’t seem to prolong PFS or overall survival.”
This research is sponsored by the Czech Lymphoma Study Group. Dr. Trneny did not disclose any conflicts of interest.
The T-cell Lymphoma Forum is held by Jonathan Wood & Associates, which is owned by the same company as this news organization.
REPORTING FROM TCLF 2019
Key clinical point:
Major finding: The 5-year progression free survival rate was 49.0% in the group receiving CHOEP, compared with 34.2% in the group receiving CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone).
Study details: A survival analysis of 462 patients with PTCL who were part of the Czech National Lymphoma Registry.
Disclosures: This research is sponsored by the Czech Lymphoma Study Group. Dr. Trneny did not disclose any conflicts of interest.
ECHELON-2: BV-CHP boosts survival 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 new research presented at the annual meeting of the American Society of Hematology.
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 with 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.
“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, with locations in New York and New Jersey.
Dr. Horwitz presented data from this trial at the ASH meeting. Results were simultaneously published in the Lancet (2018 Dec 3. doi: 10.1016/S0140-6736[18]32984-2).
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive or ALK-negative systemic anaplastic large-cell lymphoma, PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and adult T-cell leukemia/lymphoma.
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 the BV-CHP arm and the CHOP arm. 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.
In all, 89% of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P = .0032). The complete response rates were 68% and 56%, respectively (P = .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 = .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 (HR = 0.66, P = .0244).
Dr. Horwitz noted that this study was not powered to determine differences in PFS or OS by PTCL subtypes.
BV-CHP had a safety profile comparable with that of 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 study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.
SOURCE: Horwitz S et al. ASH 2018, Abstract 997.
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 new research presented at the annual meeting of the American Society of Hematology.
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 with 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.
“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, with locations in New York and New Jersey.
Dr. Horwitz presented data from this trial at the ASH meeting. Results were simultaneously published in the Lancet (2018 Dec 3. doi: 10.1016/S0140-6736[18]32984-2).
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive or ALK-negative systemic anaplastic large-cell lymphoma, PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and adult T-cell leukemia/lymphoma.
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 the BV-CHP arm and the CHOP arm. 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.
In all, 89% of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P = .0032). The complete response rates were 68% and 56%, respectively (P = .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 = .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 (HR = 0.66, P = .0244).
Dr. Horwitz noted that this study was not powered to determine differences in PFS or OS by PTCL subtypes.
BV-CHP had a safety profile comparable with that of 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 study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.
SOURCE: Horwitz S et al. ASH 2018, Abstract 997.
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 new research presented at the annual meeting of the American Society of Hematology.
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 with 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.
“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, with locations in New York and New Jersey.
Dr. Horwitz presented data from this trial at the ASH meeting. Results were simultaneously published in the Lancet (2018 Dec 3. doi: 10.1016/S0140-6736[18]32984-2).
ECHELON-2 (NCT01777152) enrolled 452 patients with previously untreated, CD30-positive PTCL. Subtypes included ALK-positive or ALK-negative systemic anaplastic large-cell lymphoma, PTCL not otherwise specified, angioimmunoblastic T-cell lymphoma, enteropathy-associated T-cell lymphoma, and adult T-cell leukemia/lymphoma.
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 the BV-CHP arm and the CHOP arm. 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.
In all, 89% of patients in the BV-CHP arm and 81% in the CHOP arm completed six or more cycles of their assigned treatment.
The overall response rate was 83% in the BV-CHP arm and 72% in the CHOP arm (P = .0032). The complete response rates were 68% and 56%, respectively (P = .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 = .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 (HR = 0.66, P = .0244).
Dr. Horwitz noted that this study was not powered to determine differences in PFS or OS by PTCL subtypes.
BV-CHP had a safety profile comparable with that of 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 study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.
SOURCE: Horwitz S et al. ASH 2018, Abstract 997.
REPORTING FROM ASH 2018
Key clinical point:
Major finding: The rate of death or progression was 42% in the BV-CHP arm and 55% in the CHOP arm (hazard ratio = 0.71, P = .011), while the rate of death alone was 23% and 32%, respectively (HR = 0.66, P = .0244).
Study details: A phase 3 trial of 452 patients with peripheral T-cell lymphoma.
Disclosures: The study was funded by Seattle Genetics, Millennium Pharmaceuticals, and the National Institutes of Health. Dr. Horwitz reported relationships with Seattle Genetics, Millennium Pharmaceuticals, and other companies.
Source: Horwitz S et al. ASH 2018, Abstract 997.
FDA expands approval of brentuximab vedotin to PTCL
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
The , marking the first FDA approval of a treatment for newly-diagnosed PTCL.
The drug, which is marketed by Seattle Genetics as Adcetris, is a monoclonal antibody that binds to CD30 protein found on some cancer cells.
It was previously approved for adult patients with untreated stage III or IV classical Hodgkin lymphoma (cHL), cHL after relapse, cHL after stem cell transplant in patients at high risk for relapse or progression, systemic anaplastic large cell lymphoma (ALCL) after other treatments fail, and primary cutaneous ALCL or CD30-expressing mycosis fungoides after other treatments fail.
The expanded approval, which followed the granting of Priority Review and Breakthrough Therapy designations for the supplemental Biologic License Application, was made using the FDA’s new Real-Time Oncology Review pilot program (RTOR). This program allows for data review and communication with a sponsor prior to official application submission with the goal of speeding up the review process.
The brentuximab vedotin approval now extends to previously untreated systemic ALCL and other CD30-expressing PTCLs in combination with chemotherapy.
Approval was based on the ECHELON-2 clinical trial involving 452 patients, which demonstrated improved progression-free survival (PFS) in patients with certain types of PTCL who were treated first-line with either brentuximab vedotin plus chemotherapy with cyclophosphamide, doxorubicin, prednisone (CHP), or standard chemotherapy with CHP and vincristine (CHOP). Median PFS was 48 months vs. 21 months in the groups, respectively (hazard ratio, 0.71).
The FDA advises health care providers to “monitor patients for infusion reactions, life-threatening allergic reactions (anaphylaxis), neuropathy, fever, gastrointestinal complications, and infections,” according to a press release announcing the approval, which also states that patients should be monitored for tumor lysis syndrome, serious skin reactions, pulmonary toxicity, and hepatotoxicity.
The drug may cause harm to a developing fetus or newborn and should not be used in women who are pregnant or breastfeeding. A Boxed Warning regarding risk of progressive multifocal leukoencephalopathy is also included in the prescribing information.
The current standard of care for initial treatment of PTCL is multiagent chemotherapy – a treatment that “has not significantly changed in decades and is too often unsuccessful in leading to long-term remissions, underscoring the need for new treatments, ” Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center, New York, said in a statement issued by Seattle Genetics.
“With this approval, clinicians have the opportunity to transform the way newly diagnosed CD30-expressing PTCL patients are treated,” Dr. Horwitz said.
The ECHELON-2 data will be presented at the American Society of Hematology annual meeting in San Diego on Monday, Dec. 3, 2018.
When to choose stem cell transplant in PTCL
DUBROVNIK, CROATIA – , according to one expert.
The success of HSCT varies according to the subtype of PTCL and the type of transplant, Ali Bazarbachi, MD, PhD, of the American University of Beirut, Lebanon, said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL–not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.
On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).
Both auto-HSCT and allogeneic (allo) HSCT are options for patients with nonlocalized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
State of PTCL treatment
Patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired, Dr. Bazarbachi said.
He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable – localized ENKTL and anaplastic lymphoma kinase–positive (ALK-positive) ALCL.
Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
PTCL-NOS, AITL, and ALCL
For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.
In a study published in 2012, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival – compared with previous results with CHOP – in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma (J Clin Oncol. 2012 Sep 1;30[25]:3093-9; ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924).
Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.
“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients – those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”
Results from the COMPLETE study showed improved survival in patients who received consolidation with auto- or allo-HSCT, compared with patients who did not receive a transplant (Blood. 2017;130:342).
COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.
Allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, Dr. Bazarbachi said.
However, chemosensitive patients who have relapsed should receive auto-HSCT only if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.
He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
ATLL
ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative, Dr. Bazarbachi said. It is most effective in patients who have achieved a complete or partial response to induction (Blood. 2012 Aug 23;120[8]:1734-41).
However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.
Also, allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.
Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time, as frontline consolidation, after relapse, or if they have refractory disease.
Auto-HSCT “does not work in this disease,” he said. In a study published in 2014, all four ATLL patients who underwent auto-HSCT “rapidly” died (Bone Marrow Transplant. 2014 Oct;49[10]:1266-8).
ENKTL
Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.
Auto-HSCT has been shown to improve survival in these patients, and it is most effective when patients have achieved a complete response to induction (Biol Blood Marrow Transplant. 2008 Dec;14[12]:1356-64).
Allo-HSCT also is an option for frontline consolidation in patients with nonlocalized ENKTL, nasal type, Dr. Bazarbachi said.
He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should receive auto-HSCT only if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.
Patients with refractory, nonlocalized ENKTL, nasal type, should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.
Dr. Bazarbachi did not declare any conflicts of interest.
The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
DUBROVNIK, CROATIA – , according to one expert.
The success of HSCT varies according to the subtype of PTCL and the type of transplant, Ali Bazarbachi, MD, PhD, of the American University of Beirut, Lebanon, said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL–not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.
On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).
Both auto-HSCT and allogeneic (allo) HSCT are options for patients with nonlocalized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
State of PTCL treatment
Patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired, Dr. Bazarbachi said.
He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable – localized ENKTL and anaplastic lymphoma kinase–positive (ALK-positive) ALCL.
Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
PTCL-NOS, AITL, and ALCL
For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.
In a study published in 2012, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival – compared with previous results with CHOP – in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma (J Clin Oncol. 2012 Sep 1;30[25]:3093-9; ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924).
Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.
“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients – those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”
Results from the COMPLETE study showed improved survival in patients who received consolidation with auto- or allo-HSCT, compared with patients who did not receive a transplant (Blood. 2017;130:342).
COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.
Allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, Dr. Bazarbachi said.
However, chemosensitive patients who have relapsed should receive auto-HSCT only if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.
He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
ATLL
ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative, Dr. Bazarbachi said. It is most effective in patients who have achieved a complete or partial response to induction (Blood. 2012 Aug 23;120[8]:1734-41).
However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.
Also, allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.
Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time, as frontline consolidation, after relapse, or if they have refractory disease.
Auto-HSCT “does not work in this disease,” he said. In a study published in 2014, all four ATLL patients who underwent auto-HSCT “rapidly” died (Bone Marrow Transplant. 2014 Oct;49[10]:1266-8).
ENKTL
Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.
Auto-HSCT has been shown to improve survival in these patients, and it is most effective when patients have achieved a complete response to induction (Biol Blood Marrow Transplant. 2008 Dec;14[12]:1356-64).
Allo-HSCT also is an option for frontline consolidation in patients with nonlocalized ENKTL, nasal type, Dr. Bazarbachi said.
He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should receive auto-HSCT only if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.
Patients with refractory, nonlocalized ENKTL, nasal type, should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.
Dr. Bazarbachi did not declare any conflicts of interest.
The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
DUBROVNIK, CROATIA – , according to one expert.
The success of HSCT varies according to the subtype of PTCL and the type of transplant, Ali Bazarbachi, MD, PhD, of the American University of Beirut, Lebanon, said at Leukemia and Lymphoma, a meeting jointly sponsored by the University of Texas MD Anderson Cancer Center and the School of Medicine at the University of Zagreb, Croatia.
For example, autologous (auto) HSCT given as frontline consolidation can be considered the standard of care for PTCL–not otherwise specified (NOS), angioimmunoblastic T-cell lymphoma (AITL), and certain patients with anaplastic large-cell lymphoma (ALCL), according to Dr. Bazarbachi.
On the other hand, auto-HSCT should never be used in patients with adult T-cell leukemia/lymphoma (ATLL).
Both auto-HSCT and allogeneic (allo) HSCT are options for patients with nonlocalized, extranodal natural killer T-cell lymphoma (ENKTL), nasal type, but only at certain times.
State of PTCL treatment
Patients with newly diagnosed PTCL are no longer treated like patients with B-cell lymphoma, but treatment outcomes in PTCL still leave a lot to be desired, Dr. Bazarbachi said.
He noted that, with any of the chemotherapy regimens used, typically, about a third of patients are primary refractory, a third relapse, and a quarter are cured. Only two forms of PTCL are frequently curable – localized ENKTL and anaplastic lymphoma kinase–positive (ALK-positive) ALCL.
Current treatment strategies for PTCL do include HSCT, but recommendations vary. Dr. Bazarbachi made the following recommendations, supported by evidence from clinical trials.
PTCL-NOS, AITL, and ALCL
For patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, auto-HSCT as frontline consolidation can be considered the standard of care in patients who responded to induction, Dr. Bazarbachi said.
In a study published in 2012, high-dose chemotherapy and auto-HSCT as consolidation improved 5-year overall survival – compared with previous results with CHOP – in patients with ALK-negative ALCL, AITL, PTCL-NOS, and enteropathy-associated T-cell lymphoma (J Clin Oncol. 2012 Sep 1;30[25]:3093-9; ISRN Hematol. 2011 Jun 16. doi: 10.5402/2011/623924).
Allo-HSCT may also be an option for frontline consolidation in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, according to Dr. Bazarbachi.
“Allo-transplant is not dead in this indication,” he said. “But it should be either part of a clinical trial or [given] to some selected patients – those with persistent bone marrow involvement, very young patients, or patients with primary refractory disease.”
Results from the COMPLETE study showed improved survival in patients who received consolidation with auto- or allo-HSCT, compared with patients who did not receive a transplant (Blood. 2017;130:342).
COMPLETE patients with AITL or PTCL-NOS had improvements in progression-free and overall survival with HSCT. The survival advantage was “less evident” in patients with ALCL, the researchers said, but this trial included both ALK-negative and ALK-positive patients.
Allo- and auto-HSCT can be options after relapse in patients with PTCL-NOS, AITL, or ALK-negative, non-DUSP22 ALCL, Dr. Bazarbachi said.
However, chemosensitive patients who have relapsed should receive auto-HSCT only if they did not receive it frontline. Patients who have already undergone auto-HSCT can receive allo-HSCT, Dr. Bazarbachi said.
He added that refractory patients should not undergo auto-HSCT and should receive allo-HSCT only within the context of a clinical trial.
ATLL
ATLL has a dismal prognosis, but allo-HSCT as frontline consolidation is potentially curative, Dr. Bazarbachi said. It is most effective in patients who have achieved a complete or partial response to induction (Blood. 2012 Aug 23;120[8]:1734-41).
However, allo-HSCT should not be given as consolidation to ATLL patients who have received prior mogamulizumab. These patients have an increased risk of morbidity and mortality if they undergo allo-HSCT.
Also, allo-HSCT should not be given to refractory ATLL patients, although it may be an option for relapsed patients.
Dr. Bazarbachi stressed that ATLL patients should not receive auto-HSCT at any time, as frontline consolidation, after relapse, or if they have refractory disease.
Auto-HSCT “does not work in this disease,” he said. In a study published in 2014, all four ATLL patients who underwent auto-HSCT “rapidly” died (Bone Marrow Transplant. 2014 Oct;49[10]:1266-8).
ENKTL
Dr. Bazarbachi said frontline consolidation with auto-HSCT should be considered the standard of care for patients with non-localized ENKTL, nasal type.
Auto-HSCT has been shown to improve survival in these patients, and it is most effective when patients have achieved a complete response to induction (Biol Blood Marrow Transplant. 2008 Dec;14[12]:1356-64).
Allo-HSCT also is an option for frontline consolidation in patients with nonlocalized ENKTL, nasal type, Dr. Bazarbachi said.
He added that chemosensitive patients who have relapsed can receive allo-HSCT, but they should receive auto-HSCT only if they did not receive it in the frontline setting. Both types of transplant should take place when patients are in complete remission.
Patients with refractory, nonlocalized ENKTL, nasal type, should not receive auto-HSCT, but allo-HSCT is an option, Dr. Bazarbachi said.
Dr. Bazarbachi did not declare any conflicts of interest.
The Leukemia and Lymphoma meeting is organized by Jonathan Wood & Associates, which is owned by the parent company of this news organization.
EXPERT ANALYSIS FROM LEUKEMIA AND LYMPHOMA 2018