Safety of IMiD-Based Holding Therapy Before CAR T-Cell Therapy in Multiple Myeloma

Al-Ola Abdallah, MD, of the University of Kansas Medical Center, discusses a retrospective analysis from the US Myeloma Innovations Research Collaborative (USMIRC). The study asked whether immunomodulatory imide drug (IMiD)–based holding therapy can control multiple myeloma before leukapheresis without compromising T-cell collection for CAR T-cell therapy. The findings were presented at the International Myeloma Society 23rd Annual Meeting & Exposition.

Abdallah first distinguishes holding therapy from bridging therapy. Holding therapy is given before leukapheresis to maintain disease control, often while a patient waits for a manufacturing slot. Bridging therapy is given after leukapheresis, until the CAR T-cell product is ready. The study examined only holding therapy.

The analysis included 363 patients across 7 academic centers who received a commercially available CAR T-cell product: 164 received idecabtagene vicleucel (ide-cel; Abecma) and 199 received ciltacabtagene autoleucel (cilta-cel; Carvykti). Within each group, outcomes were compared by whether patients received IMiD-containing holding therapy.

Abdallah explains that preclinical data suggest agents such as lenalidomide (Revlimid) may activate T cells and natural killer cells and enhance CAR T-cell function. Some clinicians worry, however, that IMiD exposure could affect blood counts, T-cell collection, and CAR T-cell efficacy. He notes that the study found no increase in toxicity with IMiD-containing holding therapy, supporting its safe use in patients whose disease is IMiD sensitive.

Per the poster, IMiD-containing holding therapy was associated with an overall survival advantage among ide-cel recipients (HR, 0.52; 95% CI, 0.28-0.94; P = .032). Progression-free survival improvements in both cohorts were not statistically significant, and no overall survival difference was seen with cilta-cel (HR, 1.12; P = .70).

Abdallah stresses the need for larger validation cohorts to clarify the effect on safety, progression-free survival, and overall survival. He also raises a potential future role for CELMoD agents such as iberdomide (Zenbexus) and mezigdomide, either as holding therapy or as maintenance after CAR T-cell therapy.