World Health Matters: Researchers explore therapy and outcomes in PTCL

Dr Andrei Shustov (University of Washington School of Medicine, Seattle, USA) summarises the advances in T-Cell lymphoma therapy at ASH 2016, including long term data in PTCL and ALCL.

Brentuximab vedotin continues to show durable responses in the relapsed setting and as initial therapy in patients with peripheral T-cell lymphomas according to studies presented here at the Annual Meeting of the American Society of Haematology. But PTCL patients who are refractory or suffer early relapse still have a grim prognosis, research shows.

End-of-study results for a pivotal phase 2 study of brentuximab vedotin for relapsed or refractory anaplastic large B-cell lymphoma show an estimated 5-year overall survival (OS) of 60% and 5-year progression-free survival (PFS) of 39%, investigators said. The trial took place at several centers in the U.S., U.K. and Canada.

A total of 58 patients, both ALK-positive and –negative, received 1.8 mg/kg of brentuximab vedotin every 3 weeks for up to 16 cycles.

At the study’s close 5 years after the last patient’s end-of-treatment visit, with a median observation time of 71 months, the median PFS was 20 months and the median OS was not reached. For patients who had a complete response (CR), neither the median OS or PFS was reached. The median OS for those with a partial response was 12 months, researchers said.

Sixteen patients, who had a median observation time of 75 months, stayed in remission with no new therapy other than a consolidation stem cell transplant. Of those, 8 stayed on the study and in remission with no other therapy after brentuximab vedotin.

Researchers found that 33 patients experienced peripheral neuropathy, which resolved or showed improvement in 30, with 67% of those patients reporting that it resolved completely.

“These end-of-study results demonstrate that among patients with relapsed/refractory systemic ALCL, the majority of patients have achieved clinically significant durable remissions, and a subset may have been cured with single-agent brentuximab vedotin,” researchers said. “Furthermore, associated toxicities are manageable.”

In another study, with 4-year results, 26 patients had good results after receiving brentuximab vedotin with CHP — cyclophosphamide, doxorubicin and prednisone — as initial therapy for several types of peripheral T cell lymphomas. The cohort included 19 anaplastic large B-cell lymphoma patients, 2 each with peripheral T-cell lymphoma not otherwise specified, angioimmunoblastic T-cell lymphoma and adult T-cell leukemia/lymphoma, and 1 with enteropathy-associated T-cell lymphoma.

In the trial, conducted at several centers in the U.S. and U.K. and led by investigators at M.D. Anderson Cancer Center in Texas, 21 of the 26 patients on combination therapy continued to receive single-agent brentuximab vedotin, with the 26 patients overall getting a median dose of 13 cycles of BV.

A total of 18 patients remained on the study after a median observation time of 52 months. The estimated 4-year PFS was 52% and the 4-year OS was 80%. At last follow-up, 15 of 19 ALCL patients and 6 of 7 non-ALCL patients were still alive.

Nineteen, or 73%, of patients on combination therapy experienced peripheral neuropathy, with 95% having it resolve completely or improve by at least one grade.

“These 4-year durability results demonstrate that among patients with PTCL, initial therapy with BV in combination with CHP can induce long-term remissions with a tolerable safety profile,” researchers said.

An analysis of data from a 74-center, worldwide prospective database shows just how poor the outlook continues to be for patients with relapsed or refractory peripheral T-cell lymphomas. Of 937 patients who received active treatment, 47% were considered refractory and 21% relapsed. All but 3 patients received combination chemotherapy and 34 were consolidated with high-dose therapy during their first remission. Also, 99 received high-dose therapy as part of their salvage treatment.

Using what they call the largest cohort of prospectively collected data on patients with aggressive T-cell lymphomas, researchers found that, after a median follow-up of 38 months, 440 patients had died, with a median survival after relapse or refractory disease (SAR) of 5.8 months. The 3-year SAR for relapse was 28% and 21% for refractory disease.

Patients who responded to salvage therapy and were consolidated with autologous stem cell transplant (ASCT) had a 3-year SAR of 48%. Researchers found that refractory disease was associated with a higher death risk, while relapse after 12 months and salvage therapy with ASCT were associated with a better outcome.

“We demonstrate that the SAR of patients with relapsed/refractory PTCL remains dismal,” researchers said. “Relapsed patients had a better outcome than those with primary refractory disease. While ASCT appeared to be beneficial for relapsed/refractory patients, only a small percentage of patients were able to undergo transplant.”

 

1. Pro B, Advani R, Brice P, et al. Five-Year Survival Data from a Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Systemic Anaplastic Large Cell Lymphoma. ASH 2016. Abstract 4144.
2. Fanale M, Horwitz S, Forero-Torres A, et al. Four-Year Survival and Durability Results of Brentuximab Vedotin in Combination with CHP in the Frontline Treatment of Patients with CD30-Expressing Peripheral T-Cell Lymphomas. ASH 2016. Abstract 2993.
3. Bellei M, Foss F, Horwitz S, et al. The Outcome of Patients with Primary Refractory or Relapsed Peripheral T-Cell Lymphoma: Analysis of 1020 Cases Registered in the Prospective T-Cell Project. ASH 2016. Abstract 921.