This prospective, multicenter phase 2 study of previously treated patients with amyloid light-chain (AL) amyloidosis aimed to examine the efficacy and safety of isatuximab, an immunoglobulin G1 kappa monoclonal antibody. Preliminary results from this analysis are reported here.
The primary objective of this trial was hematologic response. Secondary objectives included safety, organ response, progression-free survival (PFS), and overall survival (OS). Patients were required to be at least 18 years of age, have relapsed or refractory systemic AL amyloidosis, and must have received ≥1 previous lines of therapy. In addition, trial subjects must have had an Eastern Cooperative Oncology Group performance status of 0 to 2, ≥1 involved organs, not be refractory to daratumumab, N-terminal pro-B-type natriuretic peptide ≤8500 pg/mL, measurable disease activity (positive monoclonal serum immunofixation electrophoresis [IFE] or urine IFE, a serum free light chain [FLC] ratio outside the normal range [0.25-1.65], and a difference in the involved versus the uninvolved serum FLC of ≥4.5 mg/dL), and creatinine clearance ≥25 mL/min. Patients were treated with isatuximab intravenously 20 mg/kg weekly in the first 28-day cycle, followed by treatment every other week for cycles 2 to 24. The maximum number of cycles was 24.
A total of 43 patients were enrolled into the study between March 2018 and September 2019 (data cutoff, July 24, 2020). Among the 36 eligible patients, 35 received at least 1 dose of isatuximab. Previous therapies included immunomodulatory therapy (9; 25%), proteasome inhibitors (n = 32; 89%), anti-CD38 monoclonal antibody therapy (2; 6%), and high-dose therapy followed by autologous stem-cell transplant (17; 47%). Single-organ involvement was found in 56% of patients, with the remainder having ≥2 organ systems involved. Sixteen (44%) of the patients had renal involvement, and 24 (67%) had cardiac involvement. Eleven of 36 (31%) eligible patients were still receiving therapy at the data cutoff (November 12, 2020). Fifty-four (19) patients discontinued treatment. The most common reasons for discontinuation of therapy were adverse events (AEs; 21%), disease progression (26%), suboptimal response (11%), and concerns related to COVID-19 (11%). The most common AEs determined to be drug-related were infusion-related reactions (49%) of which 94% were determined to be grade 1/2; anemia (26%), the majority (89%) being grade 1; and lymphopenia (26%). The overall hematologic response rate was 77% in the patients who received at least 1 dose of isatuximab. The hematologic complete response, very good partial response (PR), and PR were observed in 3%, 54%, and 20% of patients, respectively. The 1-year estimated duration of response is 89%. One-year estimated OS is 97%, and 1-year estimated PFS is 85%.
The results from this preliminary analysis demonstrated encouraging efficacy for isatuximab use in patients with AL amyloidosis who were previously treated. Isatuximab was associated with a good safety profile, which was similar to other CD38 monoclonal antibody agents.
Abstract 728. ASH 2020. December 7, 2020. A phase II study of isatuximab (SAR650984) (NSC-795145) for patients with previously treated AL amyloidosis (SWOG S1702; NCT#03499808).