Etentamig Shows Manageable Safety and Low Severe Infection Risk in RRMM

Pooled data from 2 phase 1 trials show that etentamig (ABBV-383; AbbVie Inc) has a manageable safety profile and low incidence of grades 3 and 4 infection in patients with relapsed/refractory multiple myeloma (RRMM). The findings, presented at the 2025 International Myeloma Society Annual Meeting, suggest that low-affinity CD3 binding may improve etentamig’s toxicity profile.

Infection is the leading cause of morbidity and mortality in patients with MM treated with bispecific antibodies (BsAb) and presents a persistent challenge that necessitates the development of novel therapies. BsAbs, particularly those targeting BCMA, significantly increase infection risk due to severe B-cell aplasia and T-cell exhaustion.¹

Etentamig is a differentiated, bispecific T-cell engager targeting BCMA and CD3 comprised of a high-avidity bivalent BCMA-binding domain, a low-affinity CD3-binding domain, and a silenced Fc tail. Its design allows for reduced cytokine release syndrome and an extended half-life for convenient dosing.²

To better elucidate the safety profile of the agent, researchers looked to 2 multi-center, open-label trials (NCT03933735; NCT05650632) Evaluating patients with RRMM who received 3 or more prior lines of therapy (LoT), including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monocloncal antibody. The pooled data analysis included patients (n = 146; 60% male; median age 68 years [range 40-87]; prior LoT 4 [range 3-23]; follow-up 13 months [range 1-48]) treated with etenamig at 60 mg of every 4 weeks or 40 mg every 3 weeks. Intravenous immunoglobulin (Ig) and anti-microbial prophylaxis were used per institutional guidelines.^2-4

All-grade infections occurred in 99 patients (68%), most commonly upper respiratory infections (n = 26; 18%) and pneumonia (n = 25; 17%). Grade 3 and 4 infections were observed in 32 patients (22%), with pneumonia (n = 18; 12%) and sepsis (n = 7; 5%) most frequent. Infections led to dose interruptions in 48 patients (41%) and discontinuations in 6 patients (4%). Serious infections were reported in 35 patients (24%), primarily pneumonia (n = 17; 12%) and sepsis (n = 8; 6%), with a median time to first serious infection of 120 days (range, 3–647). Median time to first infective pneumonia was 101 days (range, 3–272). One opportunistic infection TEAE (0.7%) occurred.²

Neutropenia was the most common grade 3 or 4 hematologic TEAE, affecting 56 patients (38%). Hypogammaglobulinemia (≥ 1 postbaseline IgG < 400 mg/dL) was observed in 127 patients (87%). Infection-related deaths without intervening post-myeloma treatment occurred in 4 patients (3%), with 1 considered related to the study drug.²

These data demonstrate that etentamig has a favorable safety profile and could address a critical limitation of BCMA-directed bispecific therapies. The agent’s differentiated design may help mitigate infection-related risk while maintaining antimyeloma activity, supporting further investigation in larger, later-phase studies.

REFERENCES

1. Gerlach A. Infection risk management in patients with multiple myeloma on T-cell engaging therapies. Pharmacy Times. September 19, 2025. Accessed September 24, 2025. https://www.pharmacytimes.com/view/infection-risk-management-in-patients-with-multiple-myeloma-on-t-cell-engaging-therapies

2. Valdes C, Lichtman E, Voorhees P, et al. Infection rate profile of etentamig monotherapy in patients with relapsed/refractory multiple myeloma. Presented at: 2025 International Myeloma Society Annual Meeting. September 17, 2025, to September 20, 2025. Toronto, Canada. Abstract PA-508

3. A study of TNB-383B in participants with relapsed or refractory multiple myeloma. Clinicaltrials.gov. Updated January 13, 2025. Accessed September 24, 2025. https://clinicaltrials.gov/study/NCT03933735

4. A study to assess adverse events of intravenously (IV) infused ABBV-383 in adult participants with relapsed or refractory multiple myeloma. Clinicaltrials.gov. Updated August 28, 2025. Accessed September 24, 2025. https://clinicaltrials.gov/study/NCT05650632