A US Food and Drug Administration (FDA)-requested, unplanned, interim analyses of 2 randomized phase 3 trials that evaluated the safety and efficacy of adding the programmed cell death-1 (PD-1) inhibitor pembrolizumab to standard-of-care therapy for either previously untreated, transplant-ineligible patients with multiple myeloma or those with relapsed/refractory disease resulted in the early termination of both studies. The results of the interim analyses were published in separate reports in Lancet Haematology.1,2

In the open-label multicenter KEYNOTE-185 study (ClinicalTrials.gov Identifier: NCT02579863), 301 treatment-naïve patients had been randomly assigned 1:1 to receive either pembrolizumab plus lenalidomide and dexamethasone or lenalidomide/dexamethasone alone. Median patient age was 74 years in both study arms and all patients had Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.

With a median follow-up of 6.6 months at the time of the interim analysis, median progression-free survival (PFS), the primary endpoint of the study, had not been reached in either study arm. However, 6 treatment-related deaths attributed to cardiac arrest, cardiac failure, myocarditis, large intestine perforation, pneumonia, or pulmonary embolism were reported in patients receiving treatment with the immune checkpoint inhibitor. In contrast, only 2 patient deaths — due to upper gastrointestinal hemorrhage and respiratory failure — occurred in patients receiving lenalidomide/dexamethasone alone. The rates of serious adverse events were 54% and 39% in the experimental and control arms, respectively,

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In the open-label multicenter KEYNOTE-183 study (ClinicalTrials.gov Identifier: NCT02576977), 249 patients had been randomly assigned 1:1 to receive pomalidomide and dexamethasone with or without pembrolizumab at the time of the interim analysis. The co-primary endpoints of the study were PFS and overall survival (OS).

All study patients had received prior treatment with a least 2 lines of therapy (excluding pomalidomide), and had an ECOG performance status of 0 or 1. The median follow-up was 8.1 months, and the median patient age was 65 years in the pembrolizumab-containing arm, and 67 years for those receiving pomalidomide/dexamethasone alone.

Although no treatment-related deaths occurred in the pomalidomide/dexamethasone arm alone, 4 patient deaths were attributed to treatment of pembrolizumab-containing therapy, and in 2 cases, these were associated with myocarditis and Stevens-Johnsons syndrome. The serious adverse event rate was 63% and 46% in patients receiving treatment with and without the immune checkpoint inhibitor, respectively.

Estimated rates of 6-month PFS were 48% for patients receiving pembrolizumab-containing therapy, and 60% for those treated with pomalidomide/dexamethasone alone. Corresponding estimates of 6-month OS rates were 82% and 90%.

Following the findings of early mortality in these analyses that were not specified in the clinical trial protocols, a data monitoring committee halted enrollment in both studies, and the studies were subsequently terminated by the FDA.


  1. Usmani SZ, Schjesvold F, Oriol A, et al.  Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial [published online July 18, 2019]. Lancet Haematol. doi: 10.1016/S2352-3026(19)30109-7
  2. Mateos MV, Blacklock H, Schjesvold F, et al. Pembrolizumab plus pomalidomide and dexamethasone for patients with relapsed or refractory multiple myeloma (KEYNOTE-183): a randomised, open-label, phase 3 trial. Lancet Haematol. doi: 10.1016/S2352-3026(19)30110-3

This article originally appeared on Oncology Nurse Advisor