Refractory/Relapsed HL after ASCT: New data from the phase II trial with brentuximab vedotin

This article was recently published in the Journal Blood, written by the lead author Robert Chen, M.D, from City of Hope National Medical Centre, California describing data from a five year follow-up demonstrating patients with R/R HL who obtained complete remission with single-agent brentuximab vedotin (ADCETRIS), have achieved long-term disease control.

This article summarizes the five year, end-of-study results highlighted as below:

• The data shows median overall survival and progression-free survival to be 40.5 months and 9.3 months respectively; estimated five year overall survival and progression-free survival was 41% and 22% respectively, hence the data aids in establishing the role of ADCETRIS in improving outcomes of patients with relapsed HL
• Thirty four patients out of 102 (33%) demonstrated complete remission, with the median response duration not reached. In patients who achieved complete remission; the estimated five year overall survival and progression-free survival rate was 64% and 52% respectively.
• Thirteen of the 34 patients (38%) who achieved a complete remission were continued to be followed and were reported to remain in remission for over five years at study closure. Of these patients, four underwent consolidative hematopoietic allogeneic-SCT (allo-SCT),while in remission, and nine received no further therapy.
• The most common adverse events of any grade were peripheral sensory neuropathy, fatigue, nausea, neutropenia and diarrhea. Of the patients who experienced treatment-emergent peripheral neuropathy, 73% experienced complete resolution and 14% show improvement in symptoms.

Conclusions

The results of the trial represent a significant milestone in establishing the use of brentuximab vedotin as a standard-of-care in the relapsed or refractory classical HL setting who have previously received ASCT. The long-term safety and efficacy data from this trial lays the groundwork and supports the development of brentuximab vedotin for other classical HL settings, including the front-line setting.

The press release article can be found here.

Five-year survival and durability results of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma.

Abstract

Presented here are the 5-year, end-of-study results from the pivotal phase 2 trial of brentuximab vedotin in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) after failed hematopoietic autologous stem cell transplantation (auto-SCT). At 5 years, the overall patient population (N=102) had an estimated overall survival (OS) rate of 41% (95% CI: 31, 51) and progression-free survival (PFS) rate of 22% (95% CI: 13, 31). Patients who achieved a complete response (CR) to brentuximab vedotin (N=34) had estimated OS and PFS rates of 64% (95% CI: 48%, 80%) and 52% (95% CI: 34%, 69%), respectively. The median OS and PFS were not reached in CR patients, with 13 patients (38% of all CR patients) remaining in follow-up and in remission at study closure. Of the 13 patients, 4 received consolidative hematopoietic allogeneic-SCT (allo-SCT), and 9 (9% of all enrolled patients) remain in sustained CR without receiving any further anti-cancer therapy after treatment with brentuximab vedotin. Of the patients who experienced treatment-emergent peripheral neuropathy (PN), 88% experienced either resolution (73%) or improvement (14%) in symptoms. These 5-year follow-up data demonstrate that a subset of patients with R/R HL who obtained CR with single-agent brentuximab vedotin have achieved long-term disease control and may potentially be cured. The trial was registered at www.clinicaltrials.gov as #NCT00848926.

Press release

Seattle Genetics Inc. and Takeda Pharmaceutical Company Limited (TSE:4502) recently announced the publication and final data of ADCETRIS (brentuximab vedotin) as a single agent in an open label multicentre pivotal phase II clinical trial, evaluating its antitumor activity (safety and efficacy) in patients (n=102) with relapsed or refractory classical Hodgkin’s lymphoma (HL) in the journal Blood.ADCETRIS is an antibody-drug conjugate (ADC) directed to CD30, known to be a key driver of classical HL tumor pathogenesis. ADCETRIS is currently being evaluated in more than 70 ongoing clinical trials.

Robert Chen, M.D., from City of Hope National Medical Centre, California  and lead author of Blood manuscript said “At the time of the trial initiation, historical outcomes for HL patients who relapsed after an autologous stem cell transplant were poor, with median post progression survival of 1.3 years and for these patients allogeneic stem cell transplant (ASCT) was considered to be the only option for long term disease control. The median survival of the patients on ADCETRIS monotherapy in this pivotal phase 2 trial exceeds these historic figures and I am pleased to see the publication of the final data.”

Dirk Huebner, M.D., Executive Medical Director, Oncology Therapeutic Area Unit, of Takeda Pharmaceutical Company said “The positive final results from this trial of ADCETRIS demonstrated that of the patients who had a complete response, 38 percent achieved long-term disease control for the duration of the study.”

The press release article can be found here.