Nivolumab, Pomalidomide, and Elotuzumab Combination for Patients With R/R Multiple Myeloma

Phase 3 Results from the Checkmate 602 Study

According to phase 3 data from the Checkmate 602 study, nivolumab plus pomalidomide and dexamethasone with or without elotuzumab treatment did not demonstrate a clinical benefit among patients with relapsed/refractory (R/R) multiple myeloma (MM) compared with pomalidomide and dexamethasone treatment.

“Preclinical studies suggest that combining nivolumab, a programmed death-1 (PD-1) immune checkpoint inhibitor, with pomalidomide/dexamethasone with or without elotuzumab, an anti-signaling lymphocytic activation molecule F7 monoclonal antibody, may improve MM treatment efficacy,” hypothesized lead study author Albert Oriol, MD, PhD, Josep Carreras Leukemia Research Institute, Barcelona, Spain, and coauthors.

Eligible patients included those aged ≥ 18 years and had measurable MM after ≥ 2 prior lines of therapy, that included an immunomodulatory drug (IMiD) and proteasome inhibitor (PI), each for ≥ 2 consecutive cycles, alone or combined, and were refractory to their last line of therapy. Trial participants were randomized on a 3-to-3-to-1 basis to receive nivolumab plus pomalidomide/dexamethasone, pomalidomide/dexamethasone, or nivolumab plus pomalidomide/dexamethasone with elotuzumab. The primary end point was progression-free survival (PFS). Additionally, overall response rate (ORR) was a key secondary end point of this trial.

Results demonstrated that at a median follow-up of 16.8 months, the PFS was similar between treatment cohorts (pomalidomide/dexamethasone, 7.3 months [95% (confidence interval) CI, 6.5 to 8.4]; nivolumab plus pomalidomide/dexamethasone, 8.4 months [95% CI, 5.8 to 2.1]; nivolumab plus pomalidomide/dexamethasone with elotuzumab, 6.3 months [95% CI, 2.4 to 11.1]). Investigators also determined the ORR was similar in the pomalidomide/dexamethasone (55%), nivolumab plus pomalidomide/dexamethasone (48%), and nivolumab plus pomalidomide/dexamethasone with elotuzumab (42%) arms.

When examining the safety profile, researchers found that the nivolumab-containing arms were associated with a less favorable safety profile versus pomalidomide/dexamethasone, including a higher rate of thrombocytopenia (nivolumab plus pomalidomide/dexamethasone, 25%; nivolumab plus pomalidomide/dexamethasone with elotuzumab, 16.7%; pomalidomide/dexamethasone, 15.7%), any-grade immune-mediated adverse events (nivolumab plus pomalidomide/dexamethasone, 13.9%; nivolumab plus pomalidomide/dexamethasone with elotuzumab, 16.7%; pomalidomide/dexamethasone, 2.9%), and adverse events leading to discontinuation (nivolumab plus pomalidomide/dexamethasone, 25%; nivolumab plus pomalidomide/dexamethasone with elotuzumab, 33.3%; pomalidomide/dexamethasone, 18.6%). No new safety signals were identified.

“CheckMate 602 did not demonstrate clinical benefit of nivolumab (+/- elotuzumab) plus [pomalidomide/dexamethasone] versus [pomalidomide/dexamethasone] for patients with relapsed/refractory MM,” concluded Dr Oriol and colleagues.

Source:

Oriol A, Hájek R, Spicka I, et al. Nivolumab, pomalidomide, and elotuzumab combination regimens for treatment of relapsed and refractory multiple myeloma: results from the phase 3 CheckMate 602 study. Clin Lymph Myel & Leuk. Published online May 18, 2024. doi: 10.1016/j.clml.2024.05.014