Iberdomide Pairs With Isatuximab to Rescue MRD-Positive Patients After Transplant

For the growing share of patients with newly diagnosed multiple myeloma (NDMM) being monitored by measurable residual disease (MRD) rather than conventional response criteria alone, the hardest question has never been whether to test—it's what to do with a positive result after transplant.

First-year data from the phase 3 MIDAS trial, presented at the 23rd International Myeloma Society (IMS) Annual Meeting, offer the first real answer: Pairing itatuximab (Sarclisa; Sanofi) with the oral CELMoD iberdomide (Zenbexus; BMS) as maintenance therapy converted a meaningful share of MRD-positive patients to MRD-negative status within 12 months, with a safety profile investigators called manageable.¹

An Induction Trial That Became an MRD-Adaptation Trial

MIDAS (NCT04934475) enrolled transplant-eligible patients with NDMM (TE-NDMM) and started everyone on 6 cycles of isatuximab, carfilzomib (Kyprolis; Amgen), lenalidomide (Revlimid; BMS), and dexamethasone (Isa-KRd)—a quadruplet induction regimen whose efficacy and tolerability were reported in a separate MIDAS analysis published earlier this year in Blood.²

Patients who converted to MRD-negativity after induction went on to a response-adapted, de-escalated pathway. The patients who remained MRD-positive after Isa-KRd induction were randomized to single autologous stem cell transplant (ASCT) plus Isa-KRd consolidation (Arm C) or tandem ASCT (Arm D) and then moved to maintenance with monthly isatuximab plus daily iberdomide for up to 3 years.¹

Daratumumab plus lenalidomide maintenance already has strong randomized evidence behind it from PERSEUS (NCT03710603) and AURIGA (NCT03901963) trials, and lenalidomide alone remains the default maintenance backbone in most of the world.³ But no prior phase 3 data existed for an anti-CD38 monoclonal antibody combined with a cereblon E3 ligase modulator (CELMoD)—the newer drug class that includes iberdomide and its more potent sibling mezigdomide (BMS)—specifically in patients known to be carrying residual disease after transplant.

Iberdomide itself is still a relatively new addition to the pharmacy shelf, having earned FDA accelerated approval in combination with daratumumab and hyaluronidase-fihj and dexamethasone for relapsed/refractory disease based on deep Ikaros/Aiolos degradation and enhanced immune stimulation relative to older IMiDs.⁴

What Isa-Iber Maintenance Actually Did to MRD Status

Of 219 patients who started Isa-Iber maintenance (108 in Arm C, 111 in Arm D), 203 completed the first year of treatment. Fifty-five patients converted from MRD-positive to MRD-negative at the stringent 10⁻⁶ sensitivity threshold during that single year of maintenance.¹

Broken out by arm, MRD-negativity at 10⁻⁶ improved from 40% post-consolidation to 58% after one year of maintenance in the single-ASCT arm and from 32% to 48% in the tandem-ASCT arm. At the more commonly used 10⁻⁵ threshold, rates moved from 67% to 76% (Arm C) and from 62% to 70% (Arm D).¹

For a population defined entirely by having failed to clear disease after an already-intensive Isa-KRd induction and transplant, converting roughly a quarter of patients to deep MRD-negativity within a year is a substantial signal—particularly because MRD status, not just response category, is increasingly the metric that predicts long-term progression-free survival in this disease.

Efficacy held up regardless of transplant strategy: disease control during the first year was similar between arms, with 5 progressions and 1 death recorded in each. Investigators noted no significant safety differences between single and tandem ASCT patients going into maintenance and no unexpected toxicity signals from the isatuximab-iberomide combination itself.¹

The Safety Profile Pharmacists Will Actually Manage

The adverse event pattern during maintenance is one an oncology pharmacy team will recognize from other CELMoD- and anti-CD38-based regimens, but the specifics matter for counseling and monitoring¹:

• Neutropenia: 46% all-grade, 42% grade 3 or higher—the dominant hematologic toxicity, consistent with iberdomide's mechanism and warranting the same proactive CBC monitoring and growth-factor support algorithms used with lenalidomide- and pomalidomide-based regimens.
• Infections: 72% all-grade, 18% grade 3 or higher—a rate that underscores the importance of infection prophylaxis discussions and prompt evaluation of fever in patients on long-term anti-CD38 antibody therapy, which itself carries known hypogammaglobulinemia risk.
• Diarrhea: 19% all-grade, only 1% grade 3 or higher—generally manageable with standard antidiarrheal counseling.
• Rash: 16% all-grade, 2% grade 3 or higher.
• Peripheral neuropathy: 18% all-grade, with no grade 3 or higher events reported—a reassuring finding given how often neuropathy limits long-term maintenance adherence with other agents.

No unexpected toxicity signals emerged, and the profile was consistent across both transplant arms.

The Pharmacist's Stake In This Data

This is a maintenance-phase trial, which means it lands in the part of the treatment course that community and health-system oncology pharmacists manage most directly—refill cycles, adherence counseling, dose modifications for cytopenias, and infection surveillance over what is meant to be up to three years of continuous therapy. A few practical takeaways:

First, this is a patient-selection story as much as a drug story. Isa-Iber maintenance was tested specifically in patients who remained MRD-positive after an already aggressive quadruplet induction—arguably the population with the most to gain from treatment intensification, and the population where a pharmacist flagging a persistently positive MRD result to the treating physician could open the door to a different maintenance conversation than "continue lenalidomide as usual."

Second, the combination adds a second oral agent (iberdomide, dosed at 1 mg daily on days 1-21 of a 28-day cycle) onto a monthly subcutaneous isatuximab backbone—a regimen structure pharmacists will need to track for adherence and cycle-timing purposes distinct from standard lenalidomide maintenance dosing.

Third, with grade 3-plus neutropenia in over 40% of patients and grade 3-plus infections in nearly 1 in 5, this maintenance regimen is not a "set it and forget it" long-term therapy. It will require the same active hematologic and infectious-disease monitoring infrastructure pharmacists have built around induction-phase quadruplets, sustained over a multi-year maintenance window rather than a few months.

MIDAS remains ongoing, and these are first-year results in a trial designed to run maintenance for 3 years. But for a field that has spent the last several years establishing MRD as a decision point, this is the first randomized data showing a concrete, tolerable next step for the patients who test MRD-positive after transplant—and a preview of how CELMoD-antibody combinations may reshape the maintenance phase of myeloma care.

REFERENCES

1. Perrot A, Lambert J, Hulin C, et al. First-year results of isatuximab-iberdomide maintenance in MRD-positive newly diagnosed multiple myeloma patients included in the phase 3 MIDAS trial. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland.

2. Perrot A, Lambert J, Hulin C, et al. Isatuximab, carfilzomib, lenalidomide, and dexamethasone induction in newly diagnosed myeloma: analysis of the MIDAS trial. Blood. 2025;146(1):52-64.

3. Perrot A, Facon T, Karlin L, et al. Measurable residual disease-guided therapy in newly diagnosed myeloma. N Engl J Med. 2025. doi:10.1056/NEJMoa2505133.

4. FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma. FDA. August 16, 2026. Accessed September 24, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-iberdomide-daratumumab-and-hyaluronidase-fihj-and-dexamethasone