7500 Background: Early intervention with lenalidomide or daratumumab significantly delays disease progression to active disease in high-risk (HR) smoldering multiple myeloma (SMM) patients (pts). The BCMAxCD3 bispecific antibody elranatamab (Elra) demonstrated strong anti-MM activity with favorable safety profile in relapsed MM. Using T-cell engagers in the early stage of the disease, with a potentially less exhausted immune system, may lead to improved efficacy. Here we report initial efficacy and safety results of Elra monotherapy in HR SMM pts enrolled in the phase 2 ERASMM Study (EMN34; NCT06183489). Methods: ERASMM is an international open-label multicenter phase 2 study of Elra as single agent in adult pts with HR SMM, defined as the presence of ≥2 Mayo 2018 “20-2-20” criteria. Treatment consisted of a fixed duration (2 years) of single-agent SC Elra with priming doses of 12 mg (C1D1) and 32 mg (C1D4), followed by 76 mg on days 8 and 15 during cycle 1, 1 and 15 during cycles 2–3, and 1 during cycles 4–24 (28-day cycle). The primary objective was the rate of complete response (CR). Safety was a key secondary endpoint. Other secondary objectives included overall response rate (ORR), measurable residual disease (MRD), progression-free survival (PFS), PFS2, time to active MM, and overall survival (OS). Results: Fifty pts with previously untreated HR SMM were included from May 2024 to September 2025 in 17 centers collaborating with the European Myeloma Network. Median age was 65 years (range 58–71). All pts had HR SMM, including M-spike >20 g/L in 42 (84%), bone marrow plasma cells >20% in 36 (72%), or free-light chain ratio >20 in 33 (66%). As of December 4, 2025, the median follow-up was 10 months (range 2.3–18.23). Thirty-four (68%) patients experienced a cytokine release syndrome event, all grade 1–2, except for grade 3 events in 2 pts. No ICANS events were observed. Infections occurred in 25 (50%) pts, including 14% grade 3–4. Other common (≥20%) non-hematologic adverse events (AEs) were skin rash (34%), diarrhea (26%), AST/ALT increase (28%), fatigue (20%), and peripheral neuropathy (20%), mostly grade 1–2. Four patients discontinued treatment due to AEs, including AST/ALT increase (n=1), Guillain–Barré syndrome (n=1), and infections (n=2). The ORR was 92%, including a very good partial response or better (≥VGPR) in 82% of pts, and a complete response or better (≥CR) in 45%. The 9-month PFS and OS rates were 95% and 100%, respectively. Conclusions: In HR SMM pts, single-agent Elra was highly active, with a 92% ORR, 45% of pts achieving ≥CR, and a favorable safety profile. Data on safety and efficacy (response, MRD, PFS) will be updated for the meeting. These data support further investigation of Elra as a therapeutic option for HR SMM. Clinical trial information: NCT06183489 .
Touzeau et al. (Thu,) studied this question.