Elranatamab Shows Strong Efficacy Signal in Smoldering Multiple Myeloma

Early intervention with elranatamab-bcmm (Elrexfio) demonstrated responses and activity among patients with high-risk smoldering multiple myeloma, according to a presentation on findings from the phase 2 ERASMM (EMN34) study (NCT06183489) presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

After 6 cycles of treatment with elranatamab, the overall response rate (ORR) was 90%, which included complete responses (CRs) in 30%, very good partial responses (VGPRs) in 44%, and PRs in 16%. With a median follow-up of 14 months, the best ORR was 92%, with CRs, VGPRs, and PRs reported in 72%, 16%, and 4%, respectively. Among 29 patients with evaluable minimal residual disease (MRD) status, 90% had undetectable MRD at a threshold of 10^–6.

All patients were alive at the time of data cutoff. The progression-free survival (PFS) rate was 96% at the time of analysis, as 2 patients experienced biochemical progression; there were no instances of progression to active myeloma. Although 5 patients discontinued therapy due to toxicity, all still responded to elranatamab.

“With a median follow-up of 14 months, elranatamab demonstrated a strong efficacy signal, with an ORR of 92% and a 72% CR [rate],” presenting study author Cyrille Touzeau, MD, PhD, a professor of hematology at the University Hospital of Nantes, France, stated in the presentation. “Overall, these results support further evaluation of elranatamab in high-risk smoldering multiple myeloma.”

As part of the phase 2 ERASMM study, 50 patients with smoldering multiple myeloma and at least 2 high-risk features per 2/20/20 criteria were assigned to receive fixed-duration elranatamab subcutaneously for 2 years. Dosing consisted of 12 mg starting on cycle 1, day 1; 32 mg starting on cycle 1, day 4; and 76 mg starting on cycle 1, day 8.

The trial’s primary end point was the CR rate after 6 cycles of treatment. Safety was a secondary end point, and secondary objectives included ORR, MRD, PFS, time to SLiM/CRAB, PFS2, and overall survival. Patients 18 years and older with a diagnosis of smoldering multiple myeloma of no longer than 5 years plus measurable disease, an ECOG performance status of 0 or 1, and adequate laboratory parameters were eligible for enrollment on the trial.²

Of 50 patients who received elranatamab, 86% (n = 43) had ongoing treatment at the time of analysis. Seven (14%) patients discontinued treatment due to biochemical progression (n = 2) or adverse effects (AEs; n= 5).

The median age was 65 years (range, 42-89), and the median time from smoldering multiple myeloma diagnosis to study enrollment was 7 months (range, 3-16). Of note, 2 elements of 2/20/20 criteria were observed 76% of patients, and 24% met 3 criteria. Additionally, 19% of patients had high-risk cytogenetics per International Myeloma Society International Myeloma Working Group (IMS-IMWG) 2025 criteria, although 81% had high-risk factors per IMWG smoldering multiple myeloma 2020 criteria.

Investigators observed no new safety signals with elranatamab in the ERASMM trial. The most common non-hematologic AEs of any grade included cytokine release syndrome (CRS; 70%), infections (54%), skin rash (38%), fatigue (32%), and diarrhea (26%). The most common grade 3 toxicities were infections (14%). The most common hematologic toxicity was neutropenia, which occurred at any grade in 44% of the study population and at grade 3/4 in 40%. Five patients (10%) discontinued elranatamab due to AEs, which included Guillain-Barré syndrome (n = 1), hypertransaminasemia (n = 1), infections (n = 2), and peripheral neuropathy (n = 1).

Safety data revealed no instances of immune effector cell-associated neurotoxicity syndrome (ICANS). CRS mainly occurred at grades 1 (46%) and 2 (20%) following step-up dosing, with events lasting for a median duration of 1 day (range, 0-1). Prophylactic tocilizumab (Actemra) was given to 70% of patients; per protocol, 22 patients received pre-emptive tocilizumab.

There were no grade 4/5 infections, and 86% of patients received prophylactic Ig replacement. Additionally, 20% of patients had IgG levels that did not dip below 400 mg/dL. Overall, the rates of infections with elranatamab in smoldering multiple myeloma compared favorably with previous reports in relapsed/refractory multiple myeloma.

Disclosures: Touzeau noted receiving honoraria from AbbVie; Bristol Myers Squibb; GlaxoSmithKline; Johnson & Johnson; Menarini; Pfizer; and Sanofi. He also disclosed consulting or advisory roles with AbbVie; Bristol Myers Squibb; GlaxoSmithKline; Johnson & Johnson; Menarini; Pfizer; and Sanofi. He also noted receiving research funding from Sanofi (Inst).

References

1. Touzeau C, Schjesvold F, Cerchione C, et al. Safety and efficacy of elranatamab as early intervention in patients with high-risk smoldering myeloma: first results from the phase 2 ERASMM (EMN34) study. J Clin Oncol. 2026;44(suppl 16):7500. doi:10.1200/JCO.2026.44.16_suppl.7500
2. Use of elranatamab in patients with high-risk smoldering multiple myeloma (ERASMM). ClinicalTrials.gov. Updated October 18, 2024. Accessed May 29, 2026. https://tinyurl.com/34dx35ky