No FDA approved drugs exist for relapsed/refractory (RR) AL Amyloidosis. CAR-T is a novel approach. We report safety and efficacy from the first 23 pts in NEXICART-2, the first U.S. clinical trial of any CAR-T in RR AL Amyloidosis.
NEXICART-2 (NCT06097832) is a single-arm, multi-site U.S. Phase 1/2 trial of autologous BCMA-targeted CAR-T NXC-201 in RR AL Amyloidosis. It will enroll 40 pts. Pts have been exposed to bortezomib and anti-CD-38 antibody with persistent or relapsed disease with measurable disease (dFLC >5mg/dl or dFLC >2mg/dl with abnormal k:l ratio, or M-spike >0.5g/dl). LD was Flu/Cy. Primary endpoint is complete hematologic response (CR) (Palladini 2012, 2020, 2021). Cardiac, renal and hepatic responses were assessed by consensus criteria (Comenzo 2012; Palladini 2014).
23 pts (13 F, 10 M), median (med) age 66 yrs (range: 49 – 82) included. Med follow-up 168 days (range 63 – 463). Med prior lines 4 (range: 1 - 12); 12 (52%) prior stem cell transplant. Med dFLC 5.7 mg/dl (range: 2.0 – 31.0). Med NT-proBNP 323 ng/L (range: 61 - 2,017). 61% (14/23) cardiac disease (Diagnosis: Mayo stage I, II, IIIa, IIIb N=1,7,5,1; Enrollment: I, II, IIIa N=5,6,3, respectively). NYHA was I (N=6) and II (N=8). 30% (7/23) kidney disease, med 3g/24h (range 2 – 10g) proteinuria.