The U.S. Food and Drug Administration (FDA) placed a clinical hold on and ordered discontinuation of three clinical trials that were evaluating the PD-1 inhibitor pembrolizumab in multiple myeloma (MM):
- KEYNOTE-183 compared pembrolizumab in combination with pomalidomide and low-dose dexamethasone with pomalidomide and low-dose dexamethasone alone in patients with relapsed/refractory MM who had undergone at least two lines of prior treatment.
- KEYNOTE-185 compared pembrolizumab, lenalidomide, and low-dose dexamethasone with lenalidomide and low-dose dexamethasone alone in patients with newly diagnosed and treatment-naïve MM who were ineligible for autologous hematopoietic cell transplantation.
- KEYNOTE-023 evaluated pembrolizumab in combination with lenalidomide or carfilzomib and low-dose dexamethasone in patients with relapsed/refractory MM. (Enrollment of the carfilzomib arm will continue.)
Despite positive results in recent studies of pembrolizumab for Richter’s transformation and relapsed/refractory primary mediastinal large B-cell lymphoma, enrollment in the trials has stopped after independent safety monitors observed more deaths in the pembrolizumab combination groups than in the control groups.
The clinical hold applies only to the three combination trials and does not apply to other studies with the drug.
Pembrolizumab was FDA approved for treatment of classical Hodgkin lymphoma in May 2017.
Sources: Reuters, July 5, 2017; Merck press release, July 5, 2017.