Etentamig Improves Response, PFS in Triple-Class Exposed Myeloma

Peter Voorhees, MD, professor of cancer medicine at Atrium Health Levine Cancer Institute and associate director of Clinical Research at the Atrium Health Wake Forest Baptist Comprehensive Cancer Center, discusses the study design and outcomes of the randomized, phase 3 CERVINO study (NCT06158841) that he is presenting at the International Myeloma Society Annual Meeting this year.

The trial evaluated etentamig against standard available therapy in patients with relapsed/refractory multiple myeloma who were triple-class exposed (proteasome inhibitor, immunomodulatory drug, and anti-CD38 antibody) but anti-BCMA treatment naive, with a minimum of 2 prior lines of therapy. Patients were randomly assigned on a 1:1 basis to etentamig or investigator's choice of carfilzomib (Kyprolis) plus dexamethasone, elotuzumab (Empliciti) with pomalidomide (Pomalyst) and dexamethasone, or selinexor (Xpovio) with bortezomib (Velcade) and dexamethasone. Coprimary end points were overall response rate (ORR) and progression-free survival (PFS); key secondary end points included overall survival (OS), depth of response, and safety.

Voorhees emphasized that the population was heavily pretreated: median age was 70 years, median time from diagnosis was 5.2 years, and patients had received a median of 3 prior lines. Additionally, 52% had triple-class refractory disease, 90% were refractory to their last prior line, and 86% were refractory to CD38-directed therapy.

Both primary end points were met. ORR was 74% with etentamig vs 45.7% with standard therapy. PFS favored etentamig (HR, 0.40) at a median follow-up of approximately 11.5 months; median PFS was not reached with etentamig vs 6.2 months with standard therapy. OS data are immature, but trends favor etentamig, with 12-month OS rates of 88% vs 72% (P = .0012).

Safety findings were notable. Cytokine release syndrome (CRS) occurred in 39.5% of patients overall, dropping to 28.3% among those who received a protocol-amended single step-up dose; no grade 3 or higher CRS occurred with either strategy. Immune effector cell–associated neurotoxicity syndrome occurred in 3.6% of patients overall (0.9% with the step-up dose). Grade 3/4 infections were more frequent with etentamig (27.7% vs 19.2%), but fatal infections (1.5% vs 3.1%) and fatal treatment-emergent adverse events overall (2.6% vs 5.7%) were both lower than with standard therapy.

Voorhees noted the safety profile, including the low CRS and ICANS rates and comparatively favorable infection-related mortality for a bispecific antibody that can be easily given every 4 weeks may support use of etentamig in community and outpatient settings from the outset of treatment.