NXC-201, a novel anti-BCMA CAR T-cell therapy, has shown promising results in patients with relapsed/refractory amyloid light chain (AL) amyloidosis, according to data from a phase 1/2 trial (NCT04720313) presented at the 2023 International Myeloma Society (IMS) Annual Meeting.
Efficacy and Response Rates
The trial demonstrated a 100% hematologic overall response rate (ORR) among evaluable patients (n = 9), with 6 achieving complete responses (CR), 2 very good partial responses (VGPR), and 1 partial response (PR). Notably, at day 30, all 6 patients in CR were minimal residual disease (MRD) negative. Organ responses were observed in 5 patients, suggesting potential for broader clinical benefit.
Safety Concerns and Mortality
Despite the encouraging response rates, the study also revealed significant safety concerns. During the follow-up period, 5 patients died due to cardiac disease, including 3 with progressive disease, 1 in VGPR, and 1 in PR. An additional patient died from COVID-19 while in CR. Overall survival (OS) ranged from 3.3 months to 12.2 months among those who died.
Adverse Events
Regarding safety, 7 patients experienced cytokine release syndrome (CRS), with grades ranging from 1 to 3. The median time to CRS onset was 2 days, and the median duration was 1 day. Six of the 7 patients with CRS received tocilizumab. No instances of immune effector cell–associated neurotoxicity syndrome (ICANS) were reported. Other adverse events included neutropenia, anemia, thrombocytopenia, febrile neutropenia, infections, and hypogammaglobulinemia.
Patient Population and Treatment Protocol
The study enrolled patients with relapsed/refractory AL amyloidosis who had received at least three prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Key inclusion criteria included a platelet count of 30 x 109/L, a creatinine clearance of at least 20 mL/min, a left ventricular ejection fraction of 40% or higher, and an ECOG performance status of 0 to 2. Patients underwent lymphodepletion with fludarabine and cyclophosphamide prior to NXC-201 infusion.
Context and Implications
While BCMA-targeted CAR T-cell therapies have shown efficacy in relapsed/refractory multiple myeloma, their application in AL amyloidosis is relatively new. Eyal Lebel, MD, a senior physician and researcher at Hadassah Medical Center in Jerusalem, Israel, noted that BCMA expression on AL plasma cells is lower compared to multiple myeloma plasma cells, and patients with AL amyloidosis are often frailer due to cardiac, kidney, and multi-organ involvement. The high rate of cardiac-related deaths in this study underscores the need for careful patient selection and management when using CAR T-cell therapy in this population.
The FDA previously granted orphan drug designations to NXC-201 for multiple myeloma and AL amyloidosis.
