What’s Next in CAR T? Emerging Therapies Potentially Reshaping R/R MM

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Anito-cel represents a promising advancement in BCMA-targeted CAR T therapy with its unique small D domain design, enabling higher transduction efficiency and CAR density while reducing tonic signaling and T-cell exhaustion. The iMMAGINE-1 study demonstrated impressive efficacy with a 97% overall response rate and a 79.3% progression-free survival at 12 months in a similar patient population to CARTITUDE-1, though with fewer prior lines of therapy (median 3 vs 6). The toxicity profile appears superior with only 6% to 7% immune effector cell-associated neurotoxicity syndrome incidence, predominantly grade 1 to 2, and no observed cranial nerve palsies, demyelinating neuropathies, or parkinsonism.

Arla-cel (arlocabtagene autoleucel) targets GPRC5D, the same antigen as the bispecific antibody talquetamab, showing comparable efficacy in patients with or without prior BCMA exposure. This alternative targeting approach offers potential solutions for BCMA-resistant disease and expands treatment options for heavily pretreated patients. The dual-targeting CD19/BCMA CAR T approaches show early promise, with theoretical advantages in targeting potential myeloma stem cells expressing CD19.

The development of multiple CAR T platforms with different targets and improved safety profiles suggests a future where CAR T therapy becomes more widely applicable across diverse patient populations. If anito-cel can maintain efficacy comparable to cilta-cel while offering superior tolerability, it could represent a significant advancement in the field. The emergence of non-BCMA targets such as GPRC5D and dual-targeting strategies may address resistance mechanisms and improve long-term outcomes, potentially revolutionizing multiple myeloma treatment paradigms in the coming years.