Dr Voorhees on the Mechanism of Action of Etentamig in Multiple Myeloma

“If we want to adapt this into the community setting more broadly, I think driving down those [cytokine release syndrome] rates to as close to zero as possible with prophylactic tocilizumab is a very useful thing to do.”

Peter Voorhees, MD, chief of the Plasma Cell Disorders Division at Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, discussed safety 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.

Etentamig was designed with a low-affinity CD3-binding domain intended to mitigate the risk of cytokine release syndrome (CRS), particularly higher-grade events, while potentially preserving T-cell fitness and reducing infection risk, Voorhees explained. Although 2 BCMA-directed CAR T-cell therapies and 3 BCMA-directed bispecific antibodies are FDA approved in the United States, room for improvement remains regarding infection and CRS, Voorhees noted.

In heavily pretreated patients enrolled in a first-in-human phase 1 trial (NCT03933735) and a phase 1b dose-optimization study (NCT05650632), etentamig monotherapy produced an overall response rate (ORR) of 66%, most of which were very good partial responses or better, and a 12-month duration of response rate exceeding 70%, according to Voorhees. Grade 3/4 infections occurred in 23% of patients, and the CRS rate was 30% without prophylactic tocilizumab (Actemra) and 0% with it, he said.

In CERVINO, presented at the 23rd International Myeloma Society (IMS) Annual Meeting & Exposition, etentamig improved ORR vs SAT (74.0% vs 45.7%; difference, 28.3 percentage points; 95% CI, 18.49%-37.46%; P < .0001) and progression-free survival (median, not reached vs 6.2 months; HR, 0.40; 95% CI, 0.29-0.54; P < .0001). Among patients who received a single step-up dose followed by full dosing 3 days later and every 4 weeks thereafter (n = 113), the CRS rate was 28.3%, nearly all grade 1, Voorhees noted. Grade 2 CRS occurred in 4.4% of patients, which he called the lowest grade 2 signal seen with any BCMA-directed bispecific antibody in this population, and no grade 3 or higher events occurred. None of the 22 patients who also received prophylactic tocilizumab developed CRS.

Prophylactic tocilizumab is not required and adds cost, Voorhees acknowledged. “[I]f we’re able to [bring] more patients to these highly effective therapies, then I think we’ve won the game,” he concluded.