CELMoD-Based Maintenance Deepens Responses After ASCT in Multiple Myeloma

Iberdomide (Zenbexus) plus subcutaneous daratumumab (Darzalex Faspro) as post–autologous stem cell transplant (ASCT) maintenance therapy was generally well tolerated and produced improvements in International Myeloma Working Group (IMWG) response and measurable residual disease (MRD) status in patients with multiple myeloma, according to an initial safety analysis and interim efficacy results from the phase 2 IBEX trial (NCT06107738) presented at the 23rd Annual International Myeloma Society (IMS) Meeting & Exposition.¹

What were the interim efficacy and MRD outcomes?

Among the first 21 patients treated, 5 improved their IMWG response category after starting iberdomide plus daratumumab maintenance. Of 11 patients who were MRD positive at baseline, 8 became MRD negative at some point over the course of monitoring. Among 9 patients with at least 1 year of follow-up—all of whom were MRD positive at the start of maintenance—6 (67%) were MRD negative at their most recent assessment, and 3 (33%) had sustained MRD negativity.

What was the safety profile of the combination?

Neutropenia was the most common hematologic adverse event (AE), occurring in 76% of patients, followed by anemia (48%), thrombocytopenia (29%), and 1 thromboembolic event (5%). The severity of neutropenia was most pronounced during cycles 1 and 2, coinciding with weekly daratumumab dosing, and became less frequent by cycles 5 and 6.

Regarding non-hematologic AEs, infections occurred in 43% of patients but were mostly grade 1/2, with only 1 hospitalization; new or worsening neuropathy occurred in 38% (5 attributed to iberdomide), diarrhea in 24%, and rash in 24%. Dose reductions of iberdomide for hematologic toxicity were uncommon (15%), and the investigators noted that diarrhea was less common and less severe than is typically seen with lenalidomide (Revlimid) maintenance.

“[I]berdomide and daratumumab as maintenance therapy was generally well tolerated. The toxicities we have seen are consistent with the data that have already been reported,” lead study investigator Jeffrey A. Zonder, MD, the leader of the Barbara Ann Karmanos Cancer Institute's Multiple Myeloma and Amyloidosis Program and a professor in the Department of Oncology at Wayne State University, concluded in the presentation.¹ “We saw improvements in IMWG response and MRD status over the course of the study, and enrollment is ongoing.”

What is the IBEX trial design and population?

IBEX is a multicenter, phase 2 trial evaluating iberdomide plus subcutaneous daratumumab as post-ASCT maintenance therapy, with a planned enrollment of 42 patients evaluable for the primary end point of sustained MRD negativity. Eligible patients had received anti-CD38 antibody–containing induction, achieved at least a partial response, undergone ASCT, and remained MRD positive for 90 to 150 days after transplant. Among the first 21 patients (data cutoff, July 17, 2026), the median age was 61 years (range, 26-72), and 8 had high-risk myeloma (7 by high-risk FISH, 1 with elevated lactate dehydrogenase). The median time from ASCT was 127 days, and the starting iberdomide dose was 1.0 mg in 10 patients and 0.75 mg in 11 patients. Enrollment is ongoing, and the investigators expect to complete accrual by the end of the first quarter of 2027.

What is the significance of these findings?

Lenalidomide is a standard post-ASCT maintenance therapy; according to the investigators, adding an anti-CD38 antibody improves myeloma control. Iberdomide is a CELMoD with greater cereblon affinity than lenalidomide. The iberdomide/daratumumab combination was approved by the FDA for relapsed/refractory multiple myeloma in August 2026, and IBEX is evaluating the regimen in the post-transplant maintenance setting.²

The investigators concluded that iberdomide plus daratumumab maintenance is generally well tolerated, with a toxicity profile consistent with the individual agents, and that improvements in IMWG response and MRD status were observed. Zonder noted that longer follow-up and full enrollment will further define the regimen’s activity as maintenance therapy.

References

1. Zonder JA, Kin A, Cole CE, et al. Multi-center phase II trial of iberdomide and SC daratumumab as post-ASCT maintenance therapy in patients with multiple myeloma (the IBEX trial): initial safety analysis and interim efficacy results. Presented at: 23rd International Myeloma Society Annual Meeting; September 23-26, 2026; Glasgow, Scotland. Abstract OA-43.
2. FDA grants accelerated approval to iberdomide with daratumumab and hyaluronidase-fihj and dexamethasone for multiple myeloma. News release. August 13, 2026. Accessed September 26, 2026. https://tinyurl.com/38258auk