Etentamig Displays Durable Responses, Tolerability in R/R Multiple Myeloma

Additional benefit was seen among those treated with 3 prior lines or 4 or more prior lines of therapy, with respective ORRs of 64% and 67%, sCR/CR rates of 24% and 29%, and VGPR rates of 27% and 27%.

Differentiated B-cell maturation antigen and CD3 bispecific T-cell engager etentamig (ABBV-383) exhibited durable responses, tolerability, and low cytokine release syndrome (CRS) incidence among patients with heavily pretreated relapsed/refractory multiple myeloma, according to long-term efficacy findings from a first-in-human phase 1 study (NCT03933735) and arm A of a phase 1b study (NCT05650632) presented at the European Hematology Association 2025 Congress.

Efficacy data revealed that the objective response rate (ORR) was 66% among efficacy-evaluable patients with relapsed/refractory multiple myeloma who were treated with 40 mg or 60 mg of etentamig (n = 145). Additionally, a very good partial response (VGPR) or better rate of 54% was observed in the study. After a median duration of follow-up of 13 months (range, 1-48), the median duration of response (DOR) was not reached (NR; 95% CI, NR-NR) among responders, with a Kaplan-Meier (KM)–estimated 12-month rate of 71% (95% CI, 58.5%-80.5%).

Furthermore, responses were observed consistently across prespecified subgroups of patients with multiple myeloma. Notable benefits were observed in those 75 years or older, with an ORR of 72%, a stringent complete response (sCR)/CR rate of 33%, and a VGPR rate of 31%; Black patients had an ORR of 63%, an sCR/CR rate of 25%, and a VGPR rate of 29%; and those with high-risk cytogenetics had an ORR of 55%, an sCR/CR rate of 24%, and a VGPR rate of 24%. In each respective group, the median DOR was NR (95% CI, 8.6-NR), NR (95% CI, 6.5-NR), and NR (95% CI, 6.5-NR), with KM-estimated 12-month rates of 73% (95% CI, 45%-88%), 66% (95% CI, 31%-86%), and 57% (95% CI, 30%-78%).

Additional benefit was seen among those treated with 3 prior lines or 4 or more prior lines, with respective ORRs of 64% and 67%, sCR/CR rates of 24% and 29%, and VGPR rates of 27% and 27%. The median DOR was NR (95% CI, 11.4-NR) and NR (95% CI, NR-NR), respectively, with KM-estimated 12-month rates of 70% (95% CI, 46%-85%) vs 75% (95% CI, 57%-83%).

“Etentamig with 1 step-up dose demonstrated a low CRS incidence, durable response, and tolerability in patients with heavily pretreated [relapsed/refractory multiple myeloma],” lead author Muhamed Baljevic, MD, associate professor of Medicine in the Division of Hematology Oncology at Vanderbilt University Medical Center and director of the Multiple Myeloma Program and Vanderbilt Amyloidosis Multidisciplinary Program of Vanderbilt-Ingram Cancer Center, wrote in the presentation with study coinvestigators. “Efficacy across all subgroups was comparable and maintained, suggesting therapeutic benefits across a broad population. These results support further exploration in the ongoing phase 3 CERVINO study (NCT06158841).”

The overall median progression-free survival (PFS) was NR (95% CI, 8.7-NR). The KM estimate at 12 months was 55% (95% CI, 44.9%-63.1%). Of note, those with high-risk cytogenetics experienced a median PFS of 7.4 months (95% CI, 2.8-NR), with an estimated 12-month rate of 36% (95% CI, 18%-54%).

The pooled analysis of 2 phase 1 studies included patients 18 years or older with multiple myeloma with relapsed/refractory disease following 3 or more prior lines of therapy, including proteasome inhibition, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Patients also had an ECOG performance status of 0 to 2 and documented progression during or following the most recent treatment for the phase 1b trial.

Patients in the phase 1 trial received etentamig at a dose of 60 mg every 4 weeks or 40 mg every 3 weeks with no step-up dosing. Those in arm A of the 1b trial received one 2-mg or 4-mg step-up dose of the investigational agent and began the 60-mg dose regimen on day 4.

Patients assessed in the pooled analysis (n = 146) had a median age of 68 years (95% CI, 40-87); 60% were men. They were most commonly White (77%) or Black/African American (17%), 87% had an ECOG performance status of 1, and 53% had Revised International Staging System stage II disease at study entry. Furthermore, a total of 26% of patients had high-risk cytogenetics, 78% did not have extramedullary plasmacytoma, and 77% of patients had triple-class refractory disease. The median number of prior lines was 4 (range, 3-23).

The pooled analysis assessed long-term efficacy, safety, and tolerability. Tumor response was assessed via International Myeloma Working Group 2016 criteria. Adverse effects (AEs) were graded according to National Cancer Institute Common Terminology Criteria for Adverse Events v5.0.

Safety data revealed treatment-emergent AEs (TEAEs) occurring in 99% of patients, with 79% experiencing grade 3/4 TEAEs. The most common hematologic TEAEs included neutropenia (any grade, 51%; grade 3/4, 38%), anemia (42%; 23%), lymphopenia (29%; 25%), and thrombocytopenia (32%; 16%). The most common nonhematologic TEAEs included fatigue (32%; 0%), diarrhea (33%; 1%), and cough (25%; 1%).

Grade 3/4 infections were observed in 22% of patients, the most common of which included pneumonia (12%) and sepsis (5%). TEAEs leading to treatment discontinuation occurred in 9% of patients, with TEAEs leading to death in 9% of patients.

The CRS incidence in arm A of the phase 1b study was 30%, with 4% experiencing grade 2 CRS; no grade 3 or higher CRS events were observed. The median time to CRS onset was 22.3 hours (range, 5.5-29.6), with a median time to resolution of 20.7 hours (range, 1.8-131.7). Only 1 instance of recurring CRS was observed during step-up dosing, with no occurrences observed in cycle 2 or beyond.

Reference

Baljevic M, Voorhees P, Rodriguez C, et al. Long-term efficacy and safety of etentamig (ABBV-383), a B-cell maturation antigen (BCMA) bispecific antibody in patients with relapsed/refractory multiple myeloma (RRMM). Abstract presented at: European Hematology Association 2025 Congress; June 12-15, 2025; Milan, Italy. Abstract PF722.