Treatment of Relapsed/Refractory Myeloma (excluding T-cell redirection therapy)

Category: Treatment of Relapsed/Refractory Myeloma (excluding T-cell redirection therapy)

Infection rate profile of etentamig monotherapy in patients with relapsed/refractory multiple myeloma

(PA-508) Infection Rate Profile of Etentamig Monotherapy in Patients with Relapsed/refractory Multiple Myeloma

Friday, September 19, 2025

Cesar Rodriguez Valdes, MD

Associate Professor of Medicine
Icahn School of Medicine at Mount Sinai, New York, NY, USA

Introduction: Patients (pts) with relapsed/refractory multiple myeloma (RRMM) require novel immunotherapies with improved infection profiles. Etentamig is a differentiated B-cell maturation antigen (BCMA) x CD3 bispecific T-cell engager composed of a high-avidity bivalent BCMA-binding domain, a low-affinity CD3-binding domain to reduce cytokine release syndrome, and a silenced Fc tail for extended half-life to enable convenient dosing. The infection rates of pts treated with etentamig were evaluated in a pooled analysis from 2 ongoing studies: the first-in-human phase 1 study (NCT03933735) and the phase 1b study (NCT05650632).

Methods: Both multicenter, open-label trials enrolled adults with RRMM with ≥3 prior lines of therapy (LoT), including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. This pooled analysis includes data from pts who received etentamig 60 mg every 4 weeks (Q4W) or 40 mg Q3W.

Results: Of 146 pts enrolled from 2022–2024, 60% (n=87) were male; median (range) age, prior LoT, and duration of follow-up was 68 (40–87) years, 4 (3–23), and 13 (1–48) months, respectively. Utilization of intravenous immunoglobulin (Ig) and anti-microbial prophylaxis was per institutional guidelines. In this cohort, 99 (68%) pts experienced all-grade infections, with upper respiratory infection (n=26 [18%]) and pneumonia (n=25 [17%]) the most common. Grade 3/4 infections were reported in 32 (22%) pts; pneumonia (n=18 [12%]) and sepsis (n=7 [5%]) were the most common. Dose interruptions and discontinuations due to infection were reported in 48 (41%) and 6 (4%) pts, respectively. Within the combined term of serious infections, 35 (24%) pts experienced treatment-emergent adverse events (TEAEs), with pneumonia (n=17 [12%]) and sepsis (n=8 [6%]) being the most common; median (range) time to onset of first serious infection was 120 (3–647) days. Median (range) time to onset of first infective pneumonia was 101 (3–272) days. One (0.7%) TEAE of opportunistic infection (cytomegalovirus reactivation) was reported. Neutropenia (n=56 [38%]) was the most common Grade 3/4 hematologic TEAE. Overall, hypogammaglobulinemia (≥1 postbaseline IgG level < 400 mg/dL) was reported in 127 (87%) pts. Deaths from infections without intervening post myeloma treatment were reported in 4 (3%) pts with 1 considered related to study drug.

Conclusions: Etentamig demonstrated a manageable infection profile. Low incidence of Grade 3/4 infections suggests low-affinity CD3 binding may improve the toxicity profile of etentamig. Pts with RRMM should receive appropriate screening, prophylaxis, and be carefully monitored at frequent intervals for effective management of infections.