The FDA placed a clinical hold on three trials evaluating the PD-1 inhibitor pembrolizumab in patients with multiple myeloma (MM) following reports of patient deaths and a review of the Data Monitoring Committee.
Two trials have been placed on full clinical hold:
- KEYNOTE-183: Patients with relapsed/refractory MM received pomalidomide and low-dose dexamethasone with or without pembrolizumab.
- KEYNOTE-185: Patients with newly diagnosed and treatment-naïve MM who were ineligible for autologous hematopoietic cell transplantation received lenalidomide and low-dose dexamethasone with or without pembrolizumab.
One trial has been placed on partial clinical hold:
- KEYNOTE-023: Patients who received prior anti-MM treatment with an immunomodulatory treatment (lenalidomide, pomalidomide, or thalidomide) received pembrolizumab in combination with lenalidomide and dexamethasone.
More deaths were observed in the pembrolizumab-treated arms of KEYNOTE-183 and KEYNOTE-185, which led to a pause in new patient enrollment. The FDA determined that available data indicated that the risks of pembrolizumab plus immunomodulatory treatment outweighed any potential benefits.
All patients enrolled in KEYNOTE-183 and KEYNOTE-185 and those in the pembrolizumab cohort of KEYNOTE-023 will discontinue investigational treatment with pembrolizumab, but the clinical hold does not apply to other studies evaluating pembrolizumab treatment.
Sources: Merck press release, June 12, 2017, and July 5, 2017.