Chief Physician Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University Hangzhou, Zhejiang, China (People's Republic)
Introduction: In recent years, daratumumab has been widely applied in the treatment of systemic light-chain (AL) amyloidosis, significantly improving the prognosis of patients. As the number of CD38+ plasma cells and tumor burden in patients with AL amyloidosis is significantly lower compared to those in patients with multiple myeloma, it is crucial to determine the appropriate dose and frequency tailored for these patients. Therefore, in the present prospective, multicenter clinical trial (ChiCTR2100049253), we evaluated the efficacy and safety of low-frequency daratumumab in AL amyloidosis.
Methods: This study enrolled 48 patients with AL amyloidosis who received low-frequency daratumumab in multiple hospitals from July 2021 to May 2024. Among them, 38 were newly diagnosed patients and 10 were relapsed and refractory patients.
The dosage frequency of daratumumab was once every 2 weeks for weeks 1–8 and once every 4 weeks for weeks 9–24, with a treatment cycle of 4 weeks. After week 25, daratumumab monotherapy was maintained every 8 weeks for at most 2 years.
Results: Among the 48 patients, 60.4% had kidney involvement, 81.3% had heart involvement, and 22 (45.8%) had Mayo 2004 stage III AL amyloidosis. The percentage of patients with hematologic response ≥ very good partial response (VGPR) at 3 months was 72.1%, including 37.2% complete response (CR) and 34.9% VGPR, with an overall response rate (ORR) of 86.0%. The percentage of hematologic response ≥VGPR at 6 months was 82.1%, including 56.4% CR and 25.6% VGPR, with an ORR of 87.2%. The best hematologic ORR was 93.8%, with 56.3% (27/48) of patients achieving CR. The median time to first hematologic response was 15 days. The percentage of patients who had a cardiac response and a renal response at 6 months was 53.8% and 47.1%, respectively, and the best cardiac and renal response rates were 64.1% and 73.9%, respectively. With a median follow-up of 26.0 months (range, 1.6-39.4 months), the median overall survival (OS) and progression-free survival (PFS) were not reached in either newly diagnosed patients or relapsed and refractory patients. The 2-year OS and PFS rates of all patients were 89.6% and 83.3%, respectively. Considering the safety endpoints, 83.3% of patients experienced at least one treatment-related adverse event (AE). The most common AEs in this group were infection (23/48, 47.9%), fatigue (22/48, 45.8%), and fever (18/48, 37.5%). Constipation occurred in 12 patients (25.0%), infusion reactions in 9 patients (18.8%), and peripheral neuropathy in 8 patients (16.7%).
Conclusions: Low-frequency daratumumab regimen is an effective and safe treatment strategy for AL amyloidosis.
