Safety, tolerability, and response rates of daratumumab in relapsed AL amyloidosis: results of a phase 2 study

Abstract

Daratumumab, a monoclonal CD38 antibody, is approved in the treatment of myeloma, but its efficacy and safety in light-chain (AL) amyloidosis has not been formally studied. This prospective phase 2 trial of daratumumab monotherapy for the treatment of AL amyloidosis was designed to determine the safety, tolerability, and hematologic and clinical response. Daratumumab 16 mg/kg was administered by IV infusion once weekly for weeks 1 to 8, every 2 weeks for weeks 9 to 24, and every 4 weeks thereafter until progression or unacceptable toxicity, for up to 24 months. Twenty-two patients with previously treated AL amyloidosis were enrolled. The majority of the patients had received high-dose melphalan and stem cell transplantation and/or treatment with a proteasome inhibitor. The median time between prior therapy and trial enrollment was 9 months (range, 1-180 months). No grade 3-4 infusion-related reactions occurred. The most common grade ≥3 adverse events included respiratory infections (n = 4; 18%) and atrial fibrillation (n = 4, 18%). Hematologic complete and very-good-partial response occurred in 86% of patients. The median time to first and best hematologic response was 4 weeks and 3 months, respectively. Renal response occurred in 10 of 15 patients (67%) with renal involvement and cardiac response occurred in 7 of 14 patients (50%) with cardiac involvement. In summary, daratumumab is well tolerated in patients with relapsed AL amyloidosis and leads to rapid and deep hematologic responses and organ responses. This trial was registered at www.clinicaltrials.gov as #NCT02841033.

Conflict of interest statement

Conflict-of-interest disclosure: The authors declare no competing financial interests.

Figures

Graphical abstract

Figure 1.

Hematologic response analysis by subject number over time. (A) The number of cycles of protocol treatment is shown on the x-axis and the subject number is shown on the y-axis; hematologic response analysis is shown on individual subject bars at the end. (B) Hematologic dFLC response after 1 dose of daratumumab in relapsed AL amyloidosis.

Figure 2.

Hematologic and organ response. (A) Hematologic response by an intention-to-treat analysis. (B) Organ response.