Patients with light chain (AL) amyloidosis who were previously treated found encouraging efficacy and a good safety profile based on preliminary results from a phase 2 study of isatuximab.
In a prospective multicenter, phase 2 study of previously treated patients with immunoglobulin AL amyloidosis, the efficacy and safety of isatuximab, an IgG1k monoclonal antibody that binds with high affinity to CD38 expressed on plasma cells, were analyzed. Results from this analysis are provided in this preliminary report.
The study’s primary objective was hematologic response. Secondary objectives included safety, organ response, progression-free survival, and overall survival. Eligible patients were required to be aged ≥18 years, have relapsed or refractory systemic AL amyloidosis, ≥1 previous lines of therapy, measurable disease activity (positive monoclonal serum immunofixation electrophoresis or urine immunofixation electrophoresis, a serum-free light chain ratio outside of the normal range [0.25-1.65], and a difference in the involved vs uninvolved serum-free light chain of ≥4.5 mg/dL), ≥1 involved organs, not refractory to daratumumab, Eastern Cooperative Oncology Group performance status of 0-2, creatinine clearance ≥25 mL/min (assessed by 24-hour urine collection or estimated by the Cockcroft-Gault formula), and NT-proBNP ≤8500 pg/mL. In the first 28-day cycle, patients were treated with isatuximab intravenously 20 mg/kg weekly followed by treatment every other week for cycles 2 to 24; the maximum number of cycles was 24.
Between March 2018 and September 2019, a total of 43 patients were registered across 14 institutions (data cutoff: July 24, 2020). Among the 36 eligible patients, 35 received ≥1 doses of isatuximab. Median age of eligible patients was 70 years. Previous therapies included proteasome inhibitors (32 patients; 89%), high-dose therapy followed by autologous stem-cell transplantation (17; 47%), immunomodulatory therapy (9; 25%), and anti-CD38 monoclonal antibody therapy (2; 6%). In 53% of patients, single-organ involvement was found; the remaining patients had ≥2 organ systems involved. Sixteen (44%) patients had renal involvement, and 24 (67%) had cardiac involvement. Of patients with cardiac involvement, 29% had cardiac biomarker stage II and 38% had stage III disease as determined with the Revised Mayo Staging system. A total of 17 of 36 eligible patients (47%) at data cutoff were still receiving therapy. The current median treatment duration was 11.8 months (range, 0.3-22.1 months). In 19 patients (53% of eligible) who discontinued treatment, adverse events (26%), disease progression (21%), suboptimal response (11%), and concerns related to COVID-19 (11%) were the most common reasons for discontinuation. For this preliminary data analysis, median follow-up was 16.3 months. The most common adverse events determined to be drug-related included infusion-related reactions (50%; majority [89%] were grade I or II), anemia (25%; majority [89%] were grade I), and lymphopenia (22%). Overall hematologic response rate was 77%. Of the patients receiving ≥1 doses of isatuximab, hematologic complete response, very good partial response, and partial response were observed in 3%, 54%, and 20% of patients, respectively.
Preliminary analysis study results showed encouraging efficacy for isatuximab use in patients with AL amyloidosis who were treated previously. The use of isatuximab among these patients was associated with a good safety profile, which was similar to other CD38 monoclonal antibodies.
Reference
Abstract 728. ASH 2020. December 7, 2020. A phase II Study of isatuximab for patients with previously treated AL amyloidosis.