Isatuximab for Relapsed and/or Refractory AL Amyloidosis: Results of a Prospective Phase 2 Trial (SWOG S1702)

Isatuximab is an IgG1k monoclonal antibody that binds with high affinity to CD38 expressed on plasma cells. Anti-CD38 antibodies have shown efficacy as monotherapy and in combination in a variety of settings for patients with multiple myeloma and light chain (AL) amyloidosis. This multi-center, cooperative group phase 2 trial was designed to evaluate hematologic response, organ response, and safety of isatuximab monotherapy for the treatment of relapsed AL amyloidosis. Isatuximab at 20 mg/kg was administered intravenously weekly during the first 28-day cycle and then every other week during cycles 2-24. Forty-three patients were registered, with 35 patients being evaluable for response. The overall hematologic response rate was 77.1%, with 57% of patients achieving a VGPR or better. The median time to partial response or better was 1.1 months. Renal response occurred in 50% (7/14) of patients with renal involvement and cardiac response occurred in 57% (8/14) of patients who were evaluable utilizing NT-pro-BNP with cardiac involvement. The most common treatment related grade ≥3 adverse events included lymphopenia (n=3, 8.5%) and infection (n=2, 6%). Isatuximab demonstrated substantial efficacy in previously treated patients with AL amyloidosis and was associated with a good safety profile. This trial was registered at www.clinicaltrials.gov as NCT#03499808.