Hodgkin Lymphoma Monotherapy Improves Survival

Phase 2 clinical trial of brentuximab vedotin (Adcetris) monotherapy in relapsed or refractory classical Hodgkin lymphoma treatment shows improved survival.

Final data from a pivotal phase 2 clinical trial of brentuximab vedotin (Adcetris) monotherapy in relapsed or refractory classical Hodgkin lymphoma recently published in Blood showed promising results.

The manuscript summarized the 5-year, end-of-study results, and highlighted patients who had a complete response and were able to achieve long-term disease control. The pivotal, single-arm phase 2 trial enrolled 102 patients with relapsed or refractory classical Hodgkin lymphoma who previously received an autologous stem cell transplant (ASCT).

Participants received a median of more than 3 prior chemotherapy regimens, as the study examined the safety and efficacy of the single-agent Adcetris. The results showed that median overall survival (OS) and progression-free survival (PFS) were 40.5 months (95% confidence interval [CI]: 28.7, 61.9) and 9.3 months (95% CI: 7.1, 12,2), respectively.

Additionally, the estimated 5-year OS and PFS rates were 41% and 22%, respectively. Out of 102 patients treated with Adcetris, 34 patients (33%) achieved a complete remission, with the median response duration not reached.

The estimated 5-year OS rate in patients who had a complete remission was 64% (95% CI: 48, 50) and 52% (95% CI: 34, 69) for the estimated 5-years PFS rate.

“At the time of trial initiation, historical outcomes for Hodgkin lymphoma patients who relapsed after an autologous stem cell transplant were poor, with median post-progression survival of 1.3 years, and the only long-term disease control option for these patients was considered to be an allogeneic stem cell transplant,” said lead study author Robert Chen, MD. “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.”

Of the 34 patients who had achieved a complete remission, 13 (38%) continued to be followed and remained in remission for more than 5 years at the study closure. Out of 13 patients, 4 underwent consolidative allogeneic stem cell transplants while in remission, and 9 did not receive any further therapy.

“The positive final results from this trial of Adcetris demonstrated that of the patients who had a complete response, 38% achieved long-term disease control for the duration of the study,” said Dirk Huebner, MD, executive medical director, Oncology Therapeutic Area Unit at Takeda Pharmaceutical Company. “In addition, the median overall survival of 40.5 months and progression-free survival of 9.3 months observed across the trial further establish the role of Adcetris in improving outcomes for patients with relapsed Hodgkin lymphoma.”

The most common adverse events of any grade in the study was sensory neuropathy, fatigue, nausea, neutropenia, and diarrhea. Treatment-induced peripheral neuropathy affected 56 patients (55%), but 88% of these patients experienced improvements in their peripheral neuropathy symptoms, including 73% with complete resolution.

“For over a decade, we have demonstrated out commitment to improve treatment outcomes in Hodgkin lymphoma through numerous clinical trials evaluating novel therapeutic approaches,” said Jonathan Drachman, MD, chief medical officer and executive vice president, Research and Development at Seattle Genetics. “Today’s final publication of the Adcetris monotherapy pivotal study in Hodgkin lymphoma patients represents a significant milestone for the trial that supported approval in more than 60 countries globally and established current use as a standard-of-care in the relapsed setting. The long-term safety and efficacy data from the pivotal trial are supportive of our ongoing development of Adcetris for other classical Hodgkin lymphoma settings, including the frontline setting. Our broad clinical program is investigating Adcetris as a foundation of care for Hodgkin lymphoma and potentially other CD30-expressing malignancies.”