FDA Lifts Clinical Hold on Nivolumab Combinations for Multiple Myeloma

The FDA previously found that PD-1/PD-L1 inhibitors may increase the mortality risk for patients with multiple myeloma.

Bristol-Myers Squibb (BMS) recently announced that the FDA has lifted the partial clinical holds placed on the CheckMate-039 and CA204142 trials evaluating nivolumab (Opdivo) combination therapy for patients with relapsed/refractory multiple myeloma, according to a press release.

CheckMate-039 explored the tolerability of nivolumab and nivolumab plus daratumumab with or without promalidomide and dexamethasone. CA204142 investigated elotuzumab plus pomalidomide and low-dose dexamethasone and elotuzumab plus nivolumab in patients with multiple myeloma prior to lenalidomide treatment.

BMS reported that the decision to lift the clinical hold was based on discussions with the FDA and an agreement to change study protocols.

However, the partial clinical hold on CheckMate-602 remains and BMS said they plan to continue discussions with the FDA to determine next steps. While the study is not currently enrolling, patients who are benefiting are continuing therapy, according to the release.

In September 2017, FDA scrutiny of PD-1/PD-L1 inhibitors grew following risks observed in pembrolizumab (Keytruda) clinical trials for multiple myeloma. The FDA held the clinical trials due to evidence suggesting pembrolizumab plus immunotherapy can increase mortality risk compared with the control group.

Following the pembrolizumab trial holds, the FDA also placed a partial clinical hold on the nivolumab clinical trials for multiple myeloma. The FDA said that data from these trials showed that PD-1/PD-L1 inhibitors plus pomalidomide or lenalidomide, and PD-1/PD-L1 drugs as a monotherapy or in combination, may be harmful to these patients, BMS said in a previous press release.

At that time, Celgene also announced a partial clinical hold on 5 trials and a full clinical hold on 1 trial exploring durvalumab (Imfinizi), a PD-L1 inhibitor, in combination with immunomodulatory and chemotherapy agents in multiple myeloma and other blood cancers, such as chronic lymphocytic leukemia and diffuse large B cell lymphoma.