Checkpoint Inhibition in Multiple Myeloma After Pembrolizumab-related Clinical Trial Deaths

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Does the failure of pembrolizumab in multiple myeloma clinical trials imply checkpoint inhibition is unlikely to work for patients with the disease?
Does the failure of pembrolizumab in multiple myeloma clinical trials imply checkpoint inhibition is unlikely to work for patients with the disease?

The US Food and Drug Administration (FDA)'s clinical hold on 2 phase 3 clinical trials on pembrolizumab for multiple myeloma led the studies' sponsor, Merck, to suspend participant recruitment in both studies.

“This decision follows a review of data by the Data Monitoring Committee in which more deaths were observed in the [pembrolizumab] arms of KEYNOTE-183 and KEYNOTE-185 and which led to the pause in new patient enrollment, as announced on June 12, 2017,” a press release from Merck states.1

The risks of pembrolizumab were determined to “outweigh any potential benefit for patients with multiple myeloma,” according to the release and, as such, all patients enrolled in both trials will discontinue investigational treatment with the agent.

Does this imply checkpoint inhibition is unlikely to work in multiple myeloma?

“Anti-PD-1 alone doesn't work in myeloma,” Alexander M. Lesokhin, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, told Cancer Therapy Advisor. “Data on targeting other immune checkpoints are not yet available.”

Dr Lesokhin noted that data from a phase 2 trial of pembrolizumab with pomalidomide and dexamethasone show “an encouraging response, suggesting that combinations of multiple myeloma drugs with anti-PD-1 have value.”2

The study was the first to investigate the combination of pembrolizumab with the immunomodulatory (IMiD) drug, pomalidomide, in patients with relapsed/refractory multiple myeloma.

The 48 patients enrolled in the study had a median of 3 prior lines of therapy, a median age of 64 years, and had received both an immunomodulatory (IMiD) and a proteasome inhibitor, 73% of which were refractory to both. Seventy percent had received an autologous transplant and 62% had high-risk cytogenetics.

RELATED: Phase 2 Dendritic Cell Vaccine Trial for Multiple Myeloma

At a median follow-up of 15.6 months, progression-free survival was 17.4 months and overall survival was not reached.

Regarding the pembrolizumab studies, “it is not clear why the excess deaths occurred in the phase 3 trials,” Dr Lesokhin stated. “I think we will have to wait and see what additional analysis of the data reveals.”

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