Usmani SZ, et al. - In patients with previously untreated multiple myeloma, lenalidomide and dexamethasone with and without pembrolizumab were tested for efficacy and safety in a randomized, open-label, phase 3 trial. Researchers undertook this unplanned, Food and Drug Administration-requested, interim analysis to evaluate the benefit–risk of these regimens. KEYNOTE-185 was run at 95 medical centers across 15 countries (Australia, Canada, France, Germany, Ireland, Israel, Italy, Japan, New Zealand, Norway, Russia, South Africa, Spain, UK, and US). Eligible patients were randomly administered either pembrolizumab plus lenalidomide and dexamethasone or lenalidomide and dexamethasone alone at a 1:1 ratio. Findings revealed an unfavorable benefit–risk profile of pembrolizumab plus lenalidomide and dexamethasone for patients with newly diagnosed, previously untreated multiple myeloma. Serious adverse events were reported in 54% of patients in the pembrolizumab plus lenalidomide and dexamethasone group vs 39% of patients in the lenalidomide and dexamethasone group; pneumonia was the most common adverse event in both groups. There were six treatment-related deaths in the pembrolizumab plus lenalidomide and dexamethasone group and two in the lenalidomide and dexamethasone group; the FDA stopped the study because of the imbalance in the mortality numbers between groups. Long-term safety and survival follow-up are ongoing.