The Efficacy and Safety of Daratumumab-Based Regimens in the Initial Treatment of Amyloid Light-Chain Amyloidosis

Amyloid light-chain (AL) amyloidosis is a rare plasma cell dyscrasia. The first-line treatment options recommended in current guidelines are bortezomib-based regimens and autologous stem cell transplantation. Daratumumab's (a biologic targeting CD38) endorsement for AL amyloidosis treatment is still pending. The ANDROMEDA global multicenter phase III clinical trial confirmed the efficacy and safety of CD38 monoclonal antibodies in patients with AL amyloidosis. The CD38 monoclonal antibody used in the clinical trial was administered via the subcutaneous route with a fixed dose of 1,800 mg/dose. However, the efficacy and safety of the intravenous dosage route in the treatment of AL in the real world have rarely been reported. This study aims to contribute valuable insights to guide future treatment approaches.

This retrospective study analyzed the efficacy and safety of daratumumab-based regimens in AL amyloidosis treatment in 24 patients (median age: 68 years; male-to-female ratio: 3:1) admitted to our hospital between January 20, 2021, and August 7, 2023. Analyses included hematologic and organ responses, outcomes, and adverse effects. All patients underwent daratumumab-based therapy, wherein daratumumab was administered intravenously at a fixed dose of 16 mg/kg or 800 mg once weekly for the initial 8 weeks, every 2 weeks for weeks 9-16, and subsequently on a monthly basis from week 17 onward. Daratumumab combination therapy regimens included the VCD (bortezomib, cyclophosphamide, and dexamethasone), VD (bortezomib and dexamethasone), ID (ixazomib and dexamethasone), RD (lenalidomide and dexamethasone), PD (pomalidomide and dexamethasone), MP (melphalan and dexamethasone), and MTD regimens (melphalan, thalidomide, and dexamethasone).

Patients underwent a median of 7 treatment cycles (range: 2-12), with a hematologic overall response rate (ORR), complete response (CR) rate, median time to response (TTR), and median time to maximal response (TMR) of ≥95.4%, 47.7%, 40 days, and 90 days, respectively. The hematologic ORR was 90, 100, and 100% for patients undergoing 2, 4, and 6 courses of treatment, with ≥CR rates of 30, 50, and 61.4%, respectively. Cardiac and renal response rates, were 71.5% and 62%, with a median TTR of 57 and 112 days, and a median TMR of 90 and 135 days, respectively . Hematologic response and CR rates were significantly different between the DVCD and D+PI+DXM regimen rates (100% vs. 92.4%, p < 0.01; and 66.7% vs. 38.3%, p < 0.01, respectively). Patients were classified using the revised Mayo staging system for AL amyloidosis with 14 patients at stages I/II and 10 at III/IV. Lymphopenia was the most common hematologic adverse reaction of ≥grade 3, with no non-hematologic adverse reactions of ≥grade 3.

In the present study, Daratumumab-based regimens rapidly induce high-level hematologic responses in AL amyloidosis, significantly surpassing conventional chemotherapy regimens in cardiac and renal response rates and response speed. The treatment was well-tolerated by patients, and there were no unintended adverse reactions observed outside of clinical trials and no cases of discontinuation of either intravenous daratumumab or the chemotherapy regimen drugs it was combined with due to adverse drug reactions. In conclusion, our results indicate promising efficacy of a daratumumab-based regimen for first-line treatment of AL amyloidosis.

No relevant conflicts of interest to declare.