ASH 2015: Brentuximab vedotin data shows durable CR five years on – is this cure? Dr Robert Chen, (City of Hope, Duarte, CA, USA) discusses the five year survival data presented at ASH; who of the CR patients to watch and wait and who to go onto allo-SCT; and whether these patients are now cured. Click video image to view.

by Thomas R. Collins: Five years after the last patient’s last treatment visit, the final results are in for brentuximab vedotin’s (BV) pivotal Phase 2 study, offering perhaps the clearest view yet of BV therapy in the long term for patients with relapsed or refractory Hodgkin lymphoma (R/R HL).

Median overall survival for the 102 patients enrolled in the study was 40.5 months and median progression-free survival was 9.3 months.¹

For the 34 patients who achieved a complete response, the median overall survival and progression-free survival are not yet reached. The median response duration for those patients is not reached, either, but it ranged from 2 months to more than 72 months. ¹

Of importance, 15 patients remained in follow-up and in remission at the end of the study with a median observation time of 69.5 months. ¹

The standard of care for those with R/R HL is salvage chemotherapy and autologous stem-cell transplantation, but about half of patients will relapse after transplant. At that point, they have a grim outlook, with a median overall survival from the time of relapse of 10 to 28 months.

Investigators in the study drew attention to the best responses that were seen in this difficult patient population, in which 71% were refractory to first-line therapy and had been through an average of 3.5 chemotherapy regimens before enrolling in the trial and starting on BV. ¹

“These end-of-study results, presenting over 60 months of follow-up data, demonstrate that among heavily pre-treated patients with R/R HL, 38% of patients who obtained CR with single-agent brentuximab vedotin” — which accounts for 13% of the patient pool — “have achieved long-term disease control and may potentially be cured,” they wrote in the presentation.

“I can’t say that this brentuximab data shows cure – I think it takes a long time (to make that statement),” Dr Kerry Savage, MD, Medical Oncologist at the British Columbia Cancer Agency, said at a lymphoma session, referring to the study results. “But it certainly is encouraging that that is possible, and certainly the side effect profile is favorable.” Dr. Savage was an investigator on the trial.

Compared to the overall patient population, the 13 patients who achieved a CR and were in remission at the end of the study skewed a bit younger, toward female and toward a better ECOG score.  Their median time from initial diagnosis to the first dose of BV was 37 months — 9 months sooner than that of the 21 others who reached a CR but were not still in remission. The remission group’s time from most recent relapse to the first dose of BV was shorter as well — 1.35 months compared to 2.7 months. ¹

Of the 34 total patients who achieved CR, 6 received an allogeneic stem cell transplant. Four of these patients remained in CR at the end of the study. Of the 28 patients who did not receive an allogeneic SCT, 9, or about a third, remained in CR with no subsequent therapy. ¹

The long-term results also show that, while a large number of patients experienced peripheral neuropathy — 55% — the problem tended to improve with time. In 88%, it resolved totally or showed improvement. In 73%, there was a complete resolution.

 

Reference

1. Chen R, Gopal A, Smith S, et al. Five-Year Survival Data Demonstrating Durable Responses from a Pivotal Phase 2 Study of Brentuximab Vedotin in Patients with Relapsed or Refractory Hodgkin Lymphoma. Presented at the 57th Annual Meeting of the American Society of Hematology. 2015 Dec 5-8. Orlando FL. Abstract 2736.