First CAR T-cell therapy for AL amyloidosis

A research team investigated a novel B-cell maturation antigen (BCMA)-directed CAR T-cell product designed specifically for patients with relapsed or refractory light-chain (AL) amyloidosis. The first results were encouraging, demonstrating clinically meaningful benefit in this population.

“NXC-201 is an investigational, sterically optimised BCMA-targeting CAR T-cell therapy which can be manufactured in 10 days,” said Dr Heather J. Landau (Memorial Sloan Kettering Cancer Center, NY, USA). In the phase 1/2 NEXICART-2 trial (NCT06097832) [1], 40 participants with relapsed or refractory AL amyloidosis will receive the investigational therapy. “Participants were exposed to at least 1 prior line of therapy, including a CD38 monoclonal antibody plus a proteosome inhibitor, and had measurable haematologic disease,” Dr Landau outlined. The current analysis evaluated the safety and efficacy of NXC-201 in the first 20 treated participants.

Most participants experienced cytokine release syndrome (CRS), all of grade 1 or 2. CRS events were predictable, occurring on days 1–3 and resolving after a median of 1 day. “We did not observe ICANS or any other form of neurotoxicity,” noted Dr Landau. Although nearly all participants developed neutropenia, only 1 case of febrile neutropenia occurred. One patient died 6 months after dosing, but this was deemed unrelated to treatment. Importantly, no unexpected cardiac events were observed, an essential consideration in AL amyloidosis.

After a median follow-up of 7.8 months, 95% of the analysed participants had normalisation of disease markers. The haematologic complete response rate was 75%, with potential for improvement. “There is the potential to get this rate up to 95%,” said Dr Landau. “Also, the median time to response was only 7 days.” Organ responses were documented in 70% of the evaluable participants.

In summary, initial results with the investigational CAR T-cell product NXC-201 are promising for patients with AL amyloidosis. The trial is ongoing, and further outcomes are anticipated.

1. Landau H, et al. Initial safety and efficacy data from nexicart-2, the first US trial of a CAR T (NXC-201) in relapsed or refractory (R/R) light chain (AL) amyloidosis, nxc-201. Abstract 696, American Society of Hematology (ASH) annual meeting 2025, 6–9 December, Orlando, Florida, USA.

Medical writing support was provided by Robert van den Heuvel.
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Posted on 11 December 202522 December 2025