Elranatamab Plus Iberdomide Shows Early Efficacy in R/R Multiple Myeloma

The combination of elranatamab-bcmm (Elrexfio) and iberdomide (CC-220) demonstrated early efficacy in the form of responses with safety that aligned with known toxicities of the individual agents in patients with relapsed or refractory multiple myeloma, according to data from part 1 of the phase 1b MagnetisMM-30 trial (NCT06215118) presented during the 2025 ASH Annual Meeting.¹

At a median follow-up of 7.8 months (range, 0.7-11.3), the doublet induced an objective response rate (ORR) of 95.5% (95% CI, 77.2%-99.9%) in all evaluable patients (n = 22), which included a complete response (CR) or better rate of 45.5% and a very good partial response (VGPR) or better rate of 77.3%. Moreover, responses occurred early, with a median time to response of 1.4 months (range, 0.5-2.7).

When broken down by dose level, in those who received elranatamab at 76 mg once weekly plus 1.0 mg of iberdomide (DL1; n = 13), the ORR with the combination was 92.3% (95% CI, 64.0%-99.8%) at a median follow-up of 9.4 months (range, 0.7-11.3); the CR or better rate was 46.2% and the VGPR or better rate was 69.2%. In patients given elranatamab at 76 mg once every 2 weeks plus 1.0 mg of iberdomide (DL-1; n = 9), the ORR achieved with the doublet was 100.0% (95% CI, 66.4%-100.0%) with 44.4% of patients experiencing a CR or better and 88.9% of patients experiencing a VGPR or better. The median follow-up for this group was 5.2 months (range, 4.5-6.4).

When examining ORR by cytogenetic risk, those with standard risk (n = 11) experienced a confirmed ORR of 100% (95% CI, 71.5%-100.0%) by investigator assessment, which included CR or better and VGPR or better rates of 36.4% and 72.7%, respectively. In those determined to have high cytogenetic risk (n = 9), the ORR with the combination was slightly lower, at 88.9% (95% CI, 51.8%-99.7%); in this group, the CR or better rate was 44.4% and the VGPR or better rate was 77.8%. Two patients were noted to have missing cytogenetic risk data; these patients both experienced a CR with the regimen.

In evaluable patients (n = 17), 4 dose-limiting toxicities (DLTs) were observed; 2 occurred at DL1 (grade 3 anorexia and grade 4 neutropenia) and 2 at DL-1 (grade 3 febrile neutropenia and grade 4 neutropenia). The most common treatment-emergent adverse effects (TEAEs) experienced with the regimen included hematologic effects, particularly neutropenia (n = 17, 77.3%); infections (n = 9, 40.9%); and cytokine release syndrome (CRS) (n = 15, 68.2%). Notably, most infections were grade 2 or lower as were all cases of CRS and immune effector cell–associated neurotoxicity syndrome (ICANS) that were reported.

“[The data] demonstrate that the combination of elranatamab and iberdomide is effective and manageable in BCMA-naive patients with relapsed/refractory multiple myeloma,” Attaya Suvannasankha, MD, of Melvin and Bren Simon Comprehensive Cancer Center, Indiana University, in Indianapolis, Indiana, said in a presentation of the data. “Even with a median follow-up of just 7.8 months, the overall response rate of 95.5% and CR rate or better [rate] of 45.5% appears to favorably [compare with] the single-agent outcomes in a different population, as well as also some emerging combinations with CELMoDs.”

What inspired the launch of the phase 1b MagnetisMM-30 study?

In August 2023, the FDA granted accelerated approval to the bispecific BCMA-directed CD3 T-cell engager elranatamab for use in adult patients with relapsed or refractory multiple myeloma who have previously received at least 4 lines of therapy, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 monoclonal antibody.² The decision was supported by data from the phase 2 MagnetisMM-3 trial (NCT04649359) in which the agent induced an ORR of 57.7% (95% CI, 47.3%-67.7%) in evaluable patients (n = 97), with 82% remaining in response for at least 9 months. Updated data showed an ORR of 61.0% with a CR or better rate of 37.4%, as well as a median progression-free survival of 17.2 months and a median overall survival of 24.6 months.^3,4

Suvannasankha added that iberdomide is an oral CELMoD that has been shown to lead to better immunomodulatory activity and antiproliferative and proapoptotic activity in myeloma cells compared with IMiDs.¹ Preclinical data have shown that the agent promotes the activation and proliferation of T cells and leads to stronger T-cell engagement and better T-cell fitness, she added.

“So, based on the complementary mechanism of action, it would be rational to think that the combination may improve efficacy—particularly in patients with relapsed/refractory multiple myeloma,” Suvannasankha said. “This provided a scientific rationale for the MagentisMM-30 study.”

What is the design of the MagnetisMM-30 study?

The phase 1b, open-label, multicenter, prospective study is comprised of 2 parts: the dose-escalation and dose-optimization portions of the research. The trial enrolled patients aged 18 years or older with multiple myeloma per International Myeloma Working Group criteria and who had an ECOG performance status ranging from 0 to 1. These patients had previously received 2 to 4 lines of therapy, including at least 1 IMiD and at least 1 PI, and were relapsed or refractory to their last line of therapy. “Of note, all patients were BCMA naive,” Suvannasankha said.

Those who underwent stem cell transplant within 12 weeks of enrollment or who had active graft-vs-host disease were excluded, as were those with ongoing peripheral sensory or motor neuropathy that was grade 2 or higher or a history of peripheral motor neuropathy that was grade 3 or higher.

“In all of the dose levels, patients would first receive the standard step-up dosing of subcutaneous elranatamab according to the approved protocol,” she explained. “Then, after they completed the step-up dosing, the combination would start.” For DL1, patients received elranatamab at 76 mg once weekly paired with iberdomide at 1.0 mg once daily for 21 days out of a 28-day cycle. For DL-1, the dose of elranatamab was reduced to 76 mg every 2 weeks and the iberdomide dose was the same.

The primary end point for part 1 is DLTs during the DLT observation period. Key secondary end points include safety in the form of adverse effects (AEs) and laboratory abnormalities, ORR, CR rate, time-to-event end points, minimal residual disease negativity rate, and immunogenicity. Part 2 is designed to further examine the safety and preliminary efficacy of the combination at 2 dosing regimens.

At the ASH Annual Meeting, Suvannasankha shared preliminary findings from part 1 of the trial.

What should be known about the MagnetisMM-30 patient population?

At a data cutoff date of September 19, 2025, a total of 22 patients who have been enrolled at centers throughout the United States, Canada, and Australia. The median patient age was 68.0 years (range, 46-83); 45.5% of patients were male, more than half (68.2%) were White, and 54.5% had an ECOG performance status of 1. Moreover, patients had stage I (22.7%), II (63.6%), or III (4.5%) disease by Revised International Staging System criteria.

“Key characteristics also include 40.9% of patients with high-risk cytogenetics, 18.2% had extramedullary disease, 50% of patients were already triple-class refractory, [and] a high proportion, 77.3% of patients, had had high-dose chemotherapy and [prior] stem cell transplantation,” Suvannasankha noted. “Also, 86.4% were refractory to their prior line of therapy.”

Of the 22 patients, 13 received elranatamab at DL1 and 9 received it at DL-1. In the DL1 group, 5 patients discontinued treatment due to an AE (n = 2), progressive disease (n = 2), or death (n = 1), which was noted to not be associated with study treatment. A total of 8 patients in the DL1 group were still receiving treatment at cutoff. In the DL-1 group, all patients were still receiving treatment.

The relative dose intensity for elranatamab and iberdomide in the overall population was 78.2% (range, 33.3%-100.4%) and 74.3% (range, 36.1%-100.0%) respectively. Dose interruptions for elranatamab were required in 81.8% of patients; 81.8% of patients also required dose interruptions of iberdomide. Moreover, 54.5% of patients required dose reductions of iberdomide.

“In comparing the DL-1 and the DL1, it was clear that elranatamab relative dose intensity according to plan, was better, suggesting a better safety profile and tolerability,” Suvannasankha said.

What was learned about the toxicity profile of elranatamab plus iberdomide in this population of patients with relapsed/refractory multiple myeloma?

Suvannasankha noted that 59.1% of patients were given granulocyte colony-stimulating factor at some point in their treatment course with the combination.

Any-grade TEAEs occurred in all patients, and 86.4% of cases were grade 3 or 4 in severity. The most common TEAEs were neutropenia (any grade, 77.3%; grade 3/4, 72.7%), CRS (68.2%; 0%), fatigue (63.6%; 0%), diarrhea (50.0%; 0%), headache (45.5%; 0%), cough (45.5%; 0%), nausea (40.9%; 0%), injection site reaction (40.9%; 0%), decreased appetite (36.4%; 4.5%), anemia (31.8%; 13.6%), and lymphopenia (18.2%; 18.2%). Broken down further, in terms of CRS, 54.5% of cases were grade 1 and 13.6% were grade 2; grade 1 or 2 ICANS occurred in 4.5% and 4.5% of patients, respectively.

Moreover, 40.9% of patients experienced any-grade infections; 2 cases were grade 3, with one patient experiencing gastroenteritis Escherichia coli and the other experiencing a skin infection. The most common infections included upper respiratory tract infection (27.3%), Candida infection (13.6%), and urinary tract infection (9.1%).

What was learned about response and PFS with elranatamab plus iberdomide in myeloma?

“It is clear that the responses occurred early and continue to deepen over time. Even with a short follow-up on the DL-1, there are already several patients who have, in fact, achieved complete remission. For the DL1 patients who achieved remission, [they] continue to sustain that remission,” Suvannasankha explained. “Patients who stopped therapy include those who had very early progression, who were not even able to start the combination and already passed away from progression of disease, patients who had pancreas cancer, and also patients who progressed and eventually died from the cancer. Two patients discontinued therapy for other reasons unrelated to progression, and they continue to enjoy remission.”

What is next for MagnetisMM-30 and elranatamab plus iberdomide in this disease?

The study is ongoing and continues to recruit patients for part 2. “[We] aim to incorporate a larger number of patients and also evaluate different dose and schedule of elranatamab and iberdomide to try to balance efficacy and toxicity,” Suvannasankha concluded.

Disclosures: Suvannasankha serves in a consultancy role for Karyopharm, Bristol Myer Squibb, GlaxoSmithKline, Regeneron, Sanofi, Jannsen, and Janssen Oncology. Research funding was provided by Bristol Myers Squibb, Regeneron, GlaxoSmithKline, Pfizer, Janssen, Janssen Oncology, and Sutro.

References

1. 1.Suvannasankha A, Kaufman JL, Badros A, et al. Safety and efficacy of elranatamab in combination with iberdomide in patients with relapsed or refractory multiple myeloma: results from the phase 1b MagentisMM-30 trial. Presented at: 2025 ASH Annual Meeting; December 6-9, 2025; Orlando, FL. Abstract #100.
2. 2.FDA grants accelerated approval to elranatamab-bcmm for multiple myeloma. FDA. August 14, 2023. Accessed December 6, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-elranatamab-bcmm-multiple-myeloma
3. 3.Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnestisMM-3 trial results. Nat Med. 2023;29(9):2259-2267. doi:10.1038/s41591-023-02528-9
4. 4.Tomasson MH, Ida S, Niesvizky R, et al. Long-term survival and safety of elranatamab in patients with relapsed or refractory multiple myeloma: Update from the MagnetisMM-3 study. Hemasphere. 2024;8(7):e136. doi:10.1002/hem3.136