Photo by Larry Young
SAN FRANCISCO—A combination treatment regimen can produce durable remissions in patients newly diagnosed with peripheral T-cell lymphoma (PTCL), results of a phase 1 study suggest.
The patients received brentuximab vedotin plus cyclophosphamide, doxorubicin, and prednisolone (BV+CHP). In some cases, this was followed by BV monotherapy.
The estimated 3-year progression-free survival (PFS) for these patients was 52%, and the overall survival (OS) was 80%.
There was a high rate of peripheral neuropathy (73%), but most cases resolved or improved over time.
Steven Horwitz, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, and his colleagues presented these data as a poster at the 8th Annual T-cell Lymphoma Forum. The study was supported by Seattle Genetics and Millennium Pharmaceuticals.
The researchers presented data on 26 patients newly diagnosed with PTCL. Nineteen patients had systemic anaplastic large-cell lymphoma (ALCL; 16 ALK- and 3 ALK+), 2 had PTCL not otherwise specified, 2 had angioimmunoblastic T-cell lymphoma, 2 had adult T-cell leukemia/lymphoma, and 1 had enteropathy-associated T-cell lymphoma.
The patients’ median age was 56 (range, 21-82). Sixty-nine percent of patients had an IPI score of 2 or higher, and 73% had stage III/IV disease.
The patients received BV+CHP every 3 weeks for 6 cycles. Those who achieved at least a partial remission could go on to receive up to 10 additional cycles of single-agent BV at 1.8 mg/kg every 3 weeks.
Twenty-three patients (88%) completed all 6 cycles of BV+CHP, and 21 patients (81%) went on to receive BV monotherapy, 11 of whom (42%) received all 10 cycles.
Fifteen patients (58%) discontinued treatment, 3 due to progressive disease, 3 due to investigator decision, 6 due to adverse events, and 3 due to patient decision.
After a median observation period of 38.7 months (range, 4.6 to 44.3), 77% of patients (n=20) remained on study.
The most common adverse events (occurring in at least 30% of patients) were nausea (69%), peripheral sensory neuropathy (69%), diarrhea (62%), fatigue (58%), alopecia (54%), dyspnea (46%), constipation (35%), myalgia (31%), peripheral edema (31%), chills (31%), anemia (31%), insomnia (31%), and febrile neutropenia.
The most common grade 3 or higher adverse events (occurring in at least 10% of patients) were febrile neutropenia (31%), neutropenia (23%), anemia (15%), and pulmonary embolism (12%).
There were 6 adverse events resulting in treatment discontinuation—peripheral sensory neuropathy (n=3), abdominal pain (n=1), asthenia (n=1), and peripheral motor neuropathy (n=1).
Seventy-three percent of patients (19/26) experienced peripheral neuropathy. Thirty-seven percent (n=7) had a complete resolution of neuropathy, and 58% (n=11) had some improvement. The median time to resolution was 1.3 months. Twelve patients (63%) had ongoing neuropathy at last follow-up, but most had grade 1 (n=10).
Response and survival
The objective response rate was 100%, and the complete response rate was 88% (n=23). One patient who had a partial response at the end of combination therapy achieved a complete response after going on to single-agent BV.
Twenty-one of the 26 patients are still alive—15 with ALCL and 6 with other PTCLs. Sixteen patients have not progressed—9 with ALCL and 5 with other PTCLs.
After progression, 5 patients received BV again, and 3 received stem cell transplants (2 allogeneic and 1 autologous).
The estimated 3-year PFS was 52%, and the estimated OS was 80%. The researchers noted that these rates compare favorably with the historical 3-year PFS and OS rates of 30% and 40%, respectively.
Researchers are currently conducting a phase 3 trial comparing BV+CHP with CHOP as frontline treatment of CD30+ mature T-cell lymphomas (ECHELON-2, NCT01777152).