MELT-MM Regimen Yields Responses in Relapsed/Refractory Multiple Myeloma

Elranatamab-bcmm (Elrexfio) plus mezigdomide produced preliminary response signals in patients with relapsed/refractory multiple myeloma, according to results from the phase 1b portion of the MELT-MM trial (NCT06645678) presented at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition.¹

What was the efficacy of elranatamab plus mezigdomide?

At a data cutoff of July 31, 2026, and a median follow-up of 13.7 months (range, 8.6-19.3) from cycle 0, day 1, all 13 evaluable patients achieved a response for an overall response rate (ORR) of 100%, including a stringent complete response (sCR) in 12 patients (92.3%) and a very good partial response in 1 patient (7.7%). The median time to response was 17 days (range, 11-45), and the median time to best response was 5.6 months (range, 3.3-5.9). Responses were consistent across the mezigdomide 0.3-mg (n = 7) and 0.6-mg (n = 6) dose cohorts and across subgroups, including patients with prior T-cell engager exposure, triple-class–refractory disease, penta-refractory disease, and soft tissue extramedullary disease, all of which had a 100% ORR.

Among 11 patients with evaluable next-generation sequencing data, 10 (90.9%) achieved a measurable residual disease (MRD)–negative CR at a sensitivity of 10⁻⁵. Additionally, 10 of 13 patients remained on study, with 1 discontinuation due to patient decision and 2 due to physician decision.

What was the safety profile of the combination?

All 13 patients experienced treatment-related adverse events, including grade 3/4 events in all patients. Neutropenia was the most common hematologic event (84.6%; grade 3/4, 84.6%), followed by thrombocytopenia (53.8%). No febrile neutropenia occurred, and primary prophylaxis with pegylated granulocyte colony-stimulating factor was used.

Cytokine release syndrome (CRS) occurred in 76.9% of patients and was limited to grade 1/2, with no grade 3 or higher events. No immune effector cell–associated neurotoxicity syndrome (ICANS) was observed. The most common nonhematologic events included fatigue or weakness (84.6%), decreased appetite (53.8%), and infection (46.2%). Infections occurred in 6 patients (46.2%), with grade 3 or higher infections in 4 patients (30.8%); lower respiratory tract infection was most common (30.8%), and 2 patients (15.4%) had cytomegalovirus disease (retinitis).

What did the translational analyses show?

Patient-sample analyses supported the biological rationale for the combination. The investigators reported that mezigdomide augmented and sustained elranatamab-driven T-cell activation and effector function, with a shift toward an effector memory phenotype and renewed T-cell proliferation. Mezigdomide also counteracted elranatamab-associated checkpoint induction, with a marked reversal of TIGIT upregulation and attenuation of PD-1 upregulation, while preserving the activating receptor DNAM-1.

“Our part 1 data suggest that elranatamab with mezigdomide acts synergistically with encouraging preliminary response signals despite [our trial population] being only 13 patients,” lead study investigator Ja Min Byun MD, PhD, an associate professor at Seoul National University College of Medicine of Seoul National University Hospital, stated in the presentation.¹ “Based on our part 1 experience, we have changed the scheduling and the schema a bit for part 2, and we are actively enrolling patients from Singapore and [South Korea] right now.”

What is the MELT-MM trial design, and what comes next?

MELT-MM is a phase 1/2 trial evaluating elranatamab plus mezigdomide in patients with RRMM who had received at least 2 prior lines of therapy, including a proteasome inhibitor and lenalidomide, with an ECOG performance status of 0 to 2; prior anti-BCMA exposure was not allowed.² The phase 1b safety portion used a 3+3 dose-escalation design, with elranatamab administered at 76 mg weekly following step-up dosing and escalating doses of mezigdomide starting at 0.3 mg. Of 15 enrolled patients, 13 were treated and evaluable; 1 patient progressed during step-up dosing, and 1 withdrew consent.

The trial’s primary end point is ORR. Secondary end points include progression-free survival, overall survival, CR or better, time to response, and duration of response.

The median patient age was 69 years (range, 51-76); patients had received a median of 4 prior lines of therapy (range, 2-7) and 30.8% had prior T-cell engager exposure. Additionally, 61.5% of patients received prior autologous stem cell transplantation and 53.8% received prior treatment with anti-CD38 monoclonal antibodies.

References

1. Byun JM, Cho H, Min C-K, et al. Phase I/II study of mezigdomide and elranatamab for relapsed/refractory multiple myeloma patients (MELT-MM): updated results from part 1. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract OA-52.
2. Mezigdomide and elranatamab for relapsed and/​or refractory multiple myeloma (MELT-MM). ClinicalTrials.gov. Updated December 3, 2025. Accessed September 24, 2026. https://tinyurl.com/s29sjxec