Dr Voorhees on Eligibility Criteria for the CERVINO Trial in Multiple Myeloma

“When you see something that’s highly effective and, just as importantly, extremely safe in a more heavily pretreated patient population, you’re going to want [to] bring that earlier into the treatment continuum.”

Peter Voorhees, MD, chief of the Plasma Cell Disorders Division at Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, discussed efficacy data from the phase 3 CERVINO trial (NCT06158841) evaluating the BCMA x CD3 bispecific T-cell engager etentamig vs standard available therapies (SAT) in patients with triple-class–exposed relapsed/refractory multiple myeloma.

Eligible patients had received at least 2 prior lines, with no upper limit, and were triple-class exposed to a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, without prior BCMA-directed therapy, Voorhees explained. Patients (N = 393) were randomized to etentamig every 4 weeks or investigator’s choice of carfilzomib (Kyprolis) plus dexamethasone; selinexor (Xpovio), bortezomib (Velcade), and dexamethasone; or elotuzumab (Empliciti), pomalidomide (Pomalyst), and dexamethasone. Overall response rate (ORR) and progression-free survival (PFS) were co-primary end points.

Data from the 23rd International Myeloma Society (IMS) Annual Meeting & Exposition showed that, at a median follow-up of 11.4 months, the ORR was 74.0% with etentamig (n = 196) vs 45.7% with SAT (n = 197; difference, 28.3 percentage points; 95% CI, 18.49%-37.46%; P < .0001). Very good partial response or better rates were 63% vs 20%, and complete response or better rates were 40% vs 7%, Voorhees noted. Etentamig reduced the risk of disease progression or death by 60% (HR, 0.40; 95% CI, 0.29-0.54; P < .0001), he said.

A subset of heavily pretreated patients progresses early on BCMA-directed bispecific antibodies, and the mechanism needs clarification, Voorhees said, citing IMS data suggesting antigen escape is not the driver. Response rates rise as these agents move into earlier lines, he added.

If approved, etentamig could suit any triple-class–exposed patient with at least 2 prior lines, including frail patients and those with multiple comorbidities, according to Voorhees. With single step-up dosing, the rate of cytokine release syndrome was 28.3%, and immune effector cell–associated neurotoxicity syndrome occurred in 1 patient (0.9%). The arm’s grade 3/4 infection rate of 27.7% compares favorably with other BCMA-directed bispecific antibodies, he said.

A phase 3 trial (NCT07728188) evaluating etentamig plus pomalidomide in early relapse will launch soon, and a phase 2/3 study (NCT07095452) is exploring etentamig-based therapy in less-fit patients with newly diagnosed disease, Voorhees concluded.