A Prospective Phase II Clinical Study of Low-Frequency Daratumumab for the Treatment of Systemic Light Chain Amyloidosis

Abstract

Purpose: Systemic light chain (AL) amyloidosis is a disease caused by the misfolding of monoclonal immunoglobulins light chain to form amyloid, which is deposited in tissues and organs, resulting in structural destruction of tissues, organ dysfunction, and progressive progression. Daratumumab is a human CD38-targeting antibody that has been used for the treatment of patients with AL amyloidosis. This is a prospective, single-arm phase II clinical study designed to explore the efficacy and safety of low-frequency Daratumumab in patients with AL amyloidosis. Methods: A total of 47 patients are expected to be enrolled in this study. As of May. 01, 2023, a total of 38 patients with AL amyloidosis meeting the inclusion criteria were included. Low-frequency Daratumumab was administered at 16 mg/kg every two weeks for weeks 1-8 and every four weeks for weeks 9-24, either alone or in combination with bortezomib. The regimen may be discontinued after week 25, or Daratumumab monotherapy every eight weeks for up to two years for maintenance therapy. The efficacy of the previous treatment was assessed before each regimen of Daratumumab. Follow-up was performed every three months after treatment cessation until disease progression or death of the patient from any cause. Results: Of the included patients, 27 (71.1%) were male, with a median age of 64 years (59-71). The median number of involved organs was 2 (1-3), of which 27 (71.1%) had renal involvement, 34 (89.5%) cardiac involvement, and 6 (15.8%) hepatic involvement. 28 (73.7%) were newly diagnosed patients and 10 (26.3%) were recurrent and refractory patients. There were 25 (65.8%) Mayo 2004 stage III patients and 23 (60.6%) Mayo 2012 stage III/IV patients. The median number of treatment cycles was 5 (2-8). All patients (100%) achieved hematologic very good partial response or above (≥VGPR), of which 18 (48.6%) patients achieved hematologic complete response or above (≥CR). The median time to hematologic remission was 15.0 days (14.0-29.0 days) and the median time to hematologic CR was 92.5 days (28.0-119.3 days). 9 (40.9%) patients achieved renal remission, with a median response time of 41.0 days (29.0-87.0 days).11 (33.3%) patients achieved cardiac remission, with a median response time of 145.0 days (30.0-223.0 days). And 1 (16.7%) patient achieved hepatic remission. At a median follow-up of 11.8 months (9.8-13.7 months), median progression-free survival (PFS) and overall survival (OS) were not reached, with a 6-month PFS of 91.0% and a 6-month survival OS of 91.0%. In terms of safety, the most common adverse events were fatigue (22 cases, 57.9%), infection (18 cases, 47.4%), and fever (16 cases, 42.1%). 7 (18.4%) patients had Daratumumab-related infusion reactions. Conclusion: The results of this study showed that the low-frequency daratumumab regimen demonstrated good hematological and organ efficacy in the treatment of patients with AL amyloidosis. Patients had a high early survival rate and better safety profile.