ASCO 2025: Adding Elranatamab to Daratumumab, Lenalidomide Induces Durable Responses in Newly Diagnosed Multiple Myeloma

Elranatamab (Elrexfio; Pfizer) plus daratumumab (Darzalex; Janssen Biotech, Inc) and lenalidomide (Revlimid; Celgene Corporation; EDR) induced deep, durable responses with manageable safety in patients with newly diagnosed multiple myeloma (NDMM) who are transplant-ineligible (TI) in the MagnetisMM-6 trial (NCT05623020). The initial data from part 1 dose level G (DLG) are to be presented at the 2025 ASCO Annual Meeting.¹

Visualization of bispecific antibody attacking cell | Image Credit: © miss irine - stock.adobe.com

Elranatamab is a humanized B-cell maturation antigen (BCMA)-CD3 bispecific antibody that activates and directs T-cells to induce cytotoxic responses against myeloma cells, which yielded promising patient outcomes in multiple MagnetisMM trials, including the MagnetisMM-1 (NCT03269136) and MagnetisMM-3 studies (NCT04649359). Data from the MagnetisMM-3 trial supported its accelerated approval by the FDA for treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.^2-5

MagnetisMM-6 is a phase 3, open-label, randomized study evaluating the efficacy and safety of EDR compared with daratumumab plus lenalidomide and dexamethasone (DRd) in patients with TI NDMM. The study consists of 2 parts in which part 1 will evaluate the optimal dose of EDR in patients with NDMM or relapsed/refractory MM to identify the recommended phase 3 dose for part 2. The main outcomes measured include safety and preliminary efficacy.⁶

In DLG, a total of 37 patients (median age 75.0 years [range, 67-83]; 37.8% male; 86.5% White, 13.5% Asian) were enrolled, of whom 34 received EDR. At the median follow-up of 4.6 months (range, 1.2-6.2), 33 patients were still receiving treatment.⁶

The confirmed overall response rate (ORR) was 91.9% (95% CI, 78.1–98.3), with 81.1% of patients achieving a very good partial response (VGPR) or better. Among patients who were enrolled at least 4 months prior to the data cutoff (n = 23), the confirmed ORR was 95.7% (95% CI, 78.1–99.9), with all patients achieving a VGPR or better.⁶

Treatment-emergent adverse events (TEAEs) were manageable. The researchers reported TEAEs in 97.3% of patients, hematological TEAEs in 78.4%, and infections in 64.9%. The most commonly reported AEs were neutropenia (any grade: 70.3%; grade 3 or 4: 67.6%), cytokine release syndrome (any grade: 62.2%; grade 3 or 4: 0%), pyrexia (any grade: 35.1%; grade 3 or 4: 0%), anemia (any grade: 32.4%; grade 3 or 4: 16.2%), injection site reaction (any grade: 29.7%; grade 3 or 4: 0%), nausea (any grade: 27%; grade 3 or 4: 0%), thrombocytopenia (any grade: 13.5%; grade 3 or 4: 10.8%), and asthenia (any grade: 16.2%; grade 3 or 4: 10.8%). There was one reported case of grade 5 Candida pneumonia.⁶

The EDR regimen demonstrated manageable safety that was consistent with the known safety profile and toxicities of the agents. Enrollment is ongoing in the dose level H cohort evaluating the ER combination. Additional safety and efficacy data, including longer-term follow-up, will be presented as the study continues.

REFERENCES

1. A study to learn about the effects of the combination of elranatamab (PF-06863135), daratumumab, lenalidomide or elranatamab and lenalidomide compared with daratumumab, lenalidomide, and dexamethasone in patients with newly diagnosed multiple myeloma who are not candidates for transplant (MagnetisMM-6). Updated May 13, 2025. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT05623020

2. Lesokhin A.M., Tomasson M.H., Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. August 15, 2023. Doi:10.1038/s41591-023-02528-9

3. PF-06863135 as single agent and in combination with immunomodulatory agents in relapse/​refractory multiple myeloma. Updated March 18, 2025. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT03269136

4. MagnetisMM-3: Study of elranatamab (PF-06863135) monotherapy in participants with multiple myeloma who are refractory to at least one PI, one IMiD and one anti-CD38 mAb. Updated January 27, 2025. Accessed May 28, 2025. https://clinicaltrials.gov/study/NCT04649359

5. FDA grants accelerated approval to elranatamab-bcmm for multiple myeloma. FDA. August 14, 2023. Accessed May 28, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-elranatamab-bcmm-multiple-myeloma

6. Quach H, Pour L, Grosicki S, et al. Elranatamab in combination with daratumumab and lenalidomide (EDR) in patients with newly diagnosed multiple myeloma (NDMM) not eligible for transplant: Initial results from MagnetisMM-6 part 1. 2025 ASCO Annual Meeting. May 30, 2025, to June 3, 2025. Chiacgo, IL. Abstract 7504