Initial early results were seen for the use of chimeric antigen receptor (CAR) T-cell therapy in patients with relapsed or refractory amyloid light-chain (AL) amyloidosis in the NEXICART-2 trial. This was the first U.S. trial of CAR T-cell therapy for patients with AL amyloidosis, demonstrating safety and feasibility for this approach in this difficult-to-treat patient population. These study findings were presented at the 2025 ASCO Annual Meeting (Abstract 7508).
“For the first time, we’ve been able to see how CAR T-cell therapy can be used to treat patients with relapsed or refractory AL amyloidosis,” stated principal study investigator Shahzad Raza, MD, of the Cleveland Clinic Cancer Institute. “This early-phase study demonstrates that CAR T-cell therapy can be safely given to these patients.”
Study Methods and Results
Currently, no approved treatments exist to treat patients with relapse or refractory AL amyloidosis.
The phase Ib/II dose-escalation and –expansion NEXICART-2 study is expected to enroll 40 patients with relapsed or refractory AL amyloidosis who have received prior treatment with bortezomib and an anti-CD38 monoclonal antibody and had suboptimal responses. All patients are to receive lymphodepletion with fludarabine and cyclophosphamide prior to treatment with an autologous B-cell maturation antigen–targeted CAR T-cell product, NXC-201. The manufacturing time for the CAR T-cell product was 14 days.
Phase I has been completed with three patients treated at the 150 x 106 dose and seven treated with the 450 x 106 dose. Dose expansion for phase II continues with the 450 x 106 dose.
Of the first 10 patients, all patients achieved a rapid and deep hematologic response, with 7 achieving a complete response. Two others achieved a very good partial response, with measurable residual disease (MRD) negativity, and the last patient had a partial response. One of the nine evaluable patients had positive MRD, and all but one patient has an ongoing response; one patient died of reasons unrelated to treatment with the CAR T-cell agent. Organ responses, including cardiac responses, were observed in four of five evaluable patients.
No neurotoxicity was reported in these initial study findings, and low-grade events of cytokine-release syndrome were observed. Grade 4 neutropenia was observed in a majority of patients, and one patient reported grade 4 acute kidney injury plus grade 5 infection; however, this patient had preexisting conditions.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.
