Retreatment with a second BCMA-directed CAR T-cell therapy (ciltacabtagene autoleucel) after CELMoD-based bridging was feasible and produced early deep response in a heavily pretreated multiple myeloma patient who had previously progressed on idecabtagene vicleucel.
A 58-year-old male with high-risk IgA kappa multiple myeloma achieved a deep response lasting approximately one year after receiving idecabtagene vicleucel as sixth-line CAR T-cell therapy.
Whole genome sequencing confirmed preserved BCMA expression at relapse following prior BCMA-directed CAR T-cell therapy, supporting eligibility for a second BCMA-targeted approach.
Bridging therapy with mezigdomide, carfilzomib, and dexamethasone (a CELMoD-based regimen) was used prior to the second CAR T-cell infusion with ciltacabtagene autoleucel.
Early post-infusion assessment demonstrated a rapid and profound response, with marked declines in serum IgA and free kappa light chains following ciltacabtagene autoleucel infusion.
Treatment-related toxicities from the second CAR T-cell therapy were manageable, including grade II cytokine release syndrome and prolonged cytopenias, with no evidence of neurotoxicity.
This case supports the feasibility and clinical effectiveness of retreatment with BCMA-directed CAR T-cell therapy in heavily pretreated multiple myeloma, particularly after a durable initial CAR T-cell response.
This research describes the case of a 58-year-old man with an aggressive and difficult-to-treat form of multiple myeloma (a blood cancer) who had already received six different lines of treatment. He was given a type of gene-modified immune cell therapy called CAR T-cell therapy (using a product called idecabtagene vicleucel, or ide-cel) that initially worked well, keeping his cancer in check for about a year. When his cancer returned, his doctors faced a difficult situation: options after a second CAR T-cell failure are very limited and the outlook is generally poor. The medical team first confirmed using advanced genetic testing (whole genome sequencing) that his cancer cells still displayed the target protein (BCMA) that CAR T-cells are designed to attack — an important check, because some patients lose this target after initial CAR T-cell therapy. They then gave him a preparatory 'bridging' treatment regimen combining a newer drug called mezigdomide (a CELMoD agent) with carfilzomib and dexamethasone, before infusing a second, different CAR T-cell product called ciltacabtagene autoleucel (cilta-cel). Shortly after this second infusion, the patient showed a strong and rapid drop in cancer markers in his blood, alongside robust expansion of the new CAR T-cells. Side effects, including a moderate immune reaction (grade II cytokine release syndrome) and low blood counts, were manageable, and he did not develop neurological complications. This research suggests that receiving a second, different BCMA-targeting CAR T-cell therapy may be a viable option for carefully selected multiple myeloma patients who responded well to their first CAR T-cell treatment. The choice of bridging therapy and switching to an alternative CAR T-cell product may both play roles in achieving a good outcome. However, this is a single patient case report, so larger prospective studies are needed before firm conclusions about the best way to select patients and sequence these treatments can be drawn.
Niklas H, Bold A, Völkl S, Lang N, Truger M, Wendelin K, et al.. (2026). Early deep response to cilta-cel as 2nd CAR T-Cell therapy after CELMoD-based bridging for advanced multiple myeloma.. Annals of hematology. https://doi.org/10.1007/s00277-026-07278-5