Elranatamab Demonstrates High Response Rates and Manageable Safety in High-Risk Smoldering Multiple Myeloma

The treatment landscape for high-risk smoldering multiple myeloma (SMM) has undergone significant evolution over recent years, with growing evidence suggesting that early intervention may delay progression to active multiple myeloma. While present therapy strategies, such as lenalidomide (Revlimid; Bristol Myers Squibb) and daratumumab (Darzalex; Janssen Biotech, Inc), have demonstrated clinical benefit in this setting, there remains a growing interest in evaluating more potent immune-based approaches earlier in the disease course. Results from the phase 2 ERASMM trial (NCT06183489), presented at the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting, suggest that the BCMA × CD3 bispecific antibody elranatamab may offer substantial clinical activity in patients with high-risk SMM, producing deep responses while maintaining a manageable safety profile.¹

Moving Bispecific Antibodies Into Earlier Disease Stages

Elranatamab is a BCMA × CD3 bispecific antibody that redirects T cells to target malignant plasma cells. Previously, the agent demonstrated meaningful efficacy in relapsed or refractory multiple myeloma (RRMM), where heavily pretreated patients have often exhausted conventional treatment options.¹

ERASMM researchers hypothesized that administering a T-cell–engaging therapy earlier in the disease course, before extensive immune dysfunction develops, could improve treatment efficacy. The trial was designed to evaluate fixed-duration elranatamab monotherapy in patients with previously untreated high-risk SMM.¹

Study Design and Patient Characteristics

The ERASMM study is an international, multicenter, open-label trial enrolling adults with high-risk SMM, characterized through the presence of at least 2 Mayo Clinic 2018 20-2-20 risk criteria. Patients received subcutaneous elranatamab for a fixed treatment duration of 2 years, beginning with step-up dosing followed by maintenance administration every 4 weeks beginning in cycle 4.¹

In total, 50 patients were enrolled across 17 European Myeloma Network centers between May 2024 and September 2025. The median age was 65 years, and all patients met the criteria for high-risk disease. Most patients exhibited multiple high-risk features, including elevated M-protein levels, increased bone marrow plasma cell involvement, or abnormal free light-chain ratios.¹

Deep Responses Observed With Single-Agent Therapy

With a median follow-up of 10 months, elranatamab demonstrated substantial antimyeloma activity. The overall response rate was 92%, with 82% of patients achieving a very good partial response or better and 45% achieving a complete response or better.¹

These findings are particularly notable given that all enrolled patients had smoldering disease rather than symptomatic multiple myeloma; this highlights the potential impact of early immune-directed intervention before disease progression.¹

Early efficacy outcomes also suggested durable disease control. The 9-month progression-free survival rate was 95%, and overall survival was 100% at the time of analysis.¹

Safety Profile Consistent With Bispecific Antibody Therapy

The safety profile of elranatamab was generally consistent with prior experience in multiple myeloma and reflected known toxicities associated with BCMA-directed bispecific antibodies.¹

Cytokine release syndrome (CRS) had occurred in 68% of patients, although nearly all events were grade 1 or 2. Only 2 patients experienced grade 3 CRS, and no cases of immune effector cell-associated neurotoxicity syndrome were reported.¹

Infections occurred in 50% of patients, with grade 3 or 4 infections in 14%. Other commonly reported adverse events included skin rash, diarrhea, elevated liver enzymes, fatigue, and peripheral neuropathy, most of which were low grade.¹

Treatment discontinuation due to adverse events occurred in 4 patients and included cases related to infection, liver enzyme elevation, and Guillain-Barré syndrome.¹

Expanding the Treatment Paradigm for High-Risk Smoldering Myeloma

Prior data indicate that patients with SMM have been managed with observation until progression to symptomatic disease. Despite this, an accumulation of evidence suggests that selected high-risk patients may benefit from earlier intervention to delay or potentially prevent progression.¹

The robust response rates observed in ERASMM support continued investigation of BCMA-directed bispecific antibodies in earlier-stage disease settings. If a longer follow-up confirms durable responses and favorable outcomes, elranatamab may expand the treatment paradigm beyond relapsed disease and into high-risk precursor states.¹

A Promising Early Intervention Strategy

The initial findings from ERASMM demonstrated that fixed-duration single-agent elranatamab produced deep responses in patients with high-risk SMM, with an overall response rate of 92% and a complete response or better achieved in nearly half of treated patients.¹

Although additional follow-up is currently needed to better define long-term efficacy and safety, these results provide early evidence that BCMA-directed bispecific antibody therapy may delay disease progression when initiated before the onset of active multiple myeloma.¹

REFERENCE

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. Presented at: 2026 American Society of Clinical Oncology Annual Meeting; May 29-June 2, 2026; Chicago, IL. Abstract 7500.