Daratumumab for Relapsed or Refractory AL Amyloidosis with high Plasma Cell Burden.

Daratumumab, an anti-CD38 antibody, is effective in AL amyloidosis with low tumor burden. Data of daratumumab treatment in patients with AL amyloidosis but high tumor burden (≥ 10% bone marrow plasma cells) is limited. We report retrospective data of ten consecutive patients with high tumor burden treated with daratumumab for relapsed/refractory AL amyloidosis. The median age at diagnosis was 62.3 years, all patients had cardiac involvement, and six (60%) patients had renal involvement. Median bone marrow plasma cell infiltration was 15% (range 10%-40%), and the median difference between involved and non-involved free light-chains (dFLC) was 446 mg/L (range 102-1392 mg/L). Patients had a median of three prior lines of therapy, including bortezomib in all patients, and lenalidomide in seven (70%) patients. The median time to first hematological response was 14 days (range 7-28 days), and the median time to best hematological response was 64 days (range 7-301 days). The hematological overall response was 90%, with high-quality response (≥ very good partial remission (VGPR)) in 70% of the patients. Fifty percent of the patients had a cardiac response after a median of 3.8 months (range 0.7 - 9.1). Infusion-related adverse events ≤ grade 2 occurred in seven (70%) patients, and grade 3 adverse events in one patient. After a median follow-up time of 10 months 8 (80%) patients continued to receive daratumumab. We conclude that daratumumab is a very effective and safe treatment option in AL patients with relapsed/refractory disease, and high disease burden at diagnosis. Daratumumab leads to rapid disease control, and improvement of organ function.