Brentuximab Vedotin: Changing the Landscape for Relapsed/Refractory Hodgkin Lymphoma Patients?

For the approximately 50 percent of patients with relapsed/refractory Hodgkin lymphoma who do not respond to autologous stem cell  transplantation (auto-SCT), the antibody-drug conjugate brentuximab vedotin produced durable response and survival, according to results from a pivotal phase 2 study reported in Blood. The observed median overall survival (OS), the study authors noted, is particularly promising because these heavily treated patients – who relapsed a median of only 6.7 months from their transplant – are a particularly vulnerable population.

Study investigators, led by Ajay K. Gopal, MD, from the University of Washington and Fred Hutchinson Cancer Research Center in Seattle, evaluated the impact of brentuximab vedotin on survival and durability of response in 102 patients with relapsed/refractory HL following auto-SCT.

Brentuximab vedotin comprises an anti-CD30 antibody conjugated by a protease cleavable linker to monomethyl auristatin E, a microtubule-disrupting agent.

Patients were followed for a median of nearly three years (33.3 months) from their first dose of the study drug.

Patients responded quickly to the drug, with a median time to first response (assessed by investigators) of 5.7 weeks and a median time to complete response of 12.2 weeks. Median OS and progression-free survival (PFS) were estimated at 40.5 months and 9.3 months, respectively.

Notably, patients’ median PFS on brentuximab vedotin was longer than the median PFS on their most recent prior therapy – by a measure of more than three months (9.3 months vs. 6.1 months). Overall, 73 patients (72%) achieved an objective response, as determined by the investigators – 34 patients (33%) achieved complete remission and 39 (38%) achieved partial remission.

Achieving complete remission on brentuximab vedotin appeared to be critical for prolonged disease control: for the 34 patients who achieved a complete remission, 16 (47%) remained progression-free after a median of 53.3 months of observation. Estimated three-year OS and PFS rates in this group were 73 percent (95% CI 57%-88%) and 58 percent (95% CI 41%-76%), respectively, as well.

At the time of last follow-up, 18 patients were still on study and in remission without starting new therapy. Of those, 15 had been followed for more than four years, or more than a year after the last progression event.

“Ongoing remissions of more than four years are particularly noteworthy for a single agent in patients who had relapsed or progressed after both combination therapy and auto-SCT,” Dr. Gopal and colleagues wrote.

The investigators were also able to nail down factors that were predictive of longer survival: younger age, less functional impairment, and lower disease burden at baseline. “The associations [of these factors] with improved survival could suggest that lymphoma may best be treated with brentuximab vedotin in the minimal residual disease state, rather than waiting until frank relapse,” the authors stated, but admitted that these associations could simply reflect younger, healthier patients starting treatment earlier in their disease course relative to other patients.

Results from upcoming trials including the AETHERA trial (evaluating PFS with brentuximab vedotin relative to best supportive care in patients at risk of relapse after transplant) and the randomized, phase 3 Echelon-1 trial (evaluating brentuximab vedotin in combination with AVD versus ABVD for frontline treatment) will help inform whether use of brentuximab vedotin earlier in the disease course of HL improves outcome in a larger percentage of patients.


Reference

    Gopal AK, Chen R, Smith SE, et al. Durable remissions in a pivotal phase study of brentuximab vedotin in relapsed or refractory Hodgkin lymphoma. Blood. 2014 December 22. [Epub ahead of print]

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