Next‑Gen CAR‑T Advances and Myeloma Risk

Researchers reported multiple next‑generation CAR‑T advances: engineered CAR‑T cells secreting bifunctional fusion proteins that combine a PD‑L1 blocker with IL‑12, IL‑15 or a TGFβ trap showed PD‑L1 binding, local cytokine/receptor engagement and enhanced antitumor activity in prostate and ovarian mouse models without systemic toxicity. A separate manufacturing advance used base editing to produce universal allogeneic “BE‑CAR” products (BE‑CAR7, BE‑CAR33, BE‑CARCLL‑1) with high CAR expression, low residual TCRαβ, robust on‑target editing and defined memory/exhaustion phenotypes, advancing off‑the‑shelf CAR approaches. In multiple myeloma, validation of the International Myeloma Society’s Consensus Genomic Staging (CGS) found about 22.4% of newly diagnosed patients meet high‑risk genomic criteria, and each criterion independently predicted worse progression‑free survival. Clinically, intensive cytotoxic bridging before BCMA CAR‑T was associated with delayed neutrophil recovery, higher rates of severe late thrombocytopenia and infections, and shorter progression‑free survival, supporting consideration of less cytotoxic bridging strategies and enhanced supportive care.