Daratumumab yields rapid and deep hematologic responses in patients with heavily pretreated AL amyloidosis

• Published in: Blood 2017-08, Vol.130 (7), p.900-902
• Main Authors: Kaufman, Gregory P., Schrier, Stanley L., Lafayette, Richard A., Arai, Sally, Witteles, Ronald M., Liedtke, Michaela
• Format: Article
• Language: English
• Subjects: Aged; Amyloidosis - blood; Amyloidosis - drug therapy; Antibodies, Monoclonal - therapeutic use; Female; Humans; Immunoglobulin Light Chains - metabolism; Male; Middle Aged
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood-2017-01-763599

The majority of patients with immunoglobulin light chain amyloidosis (AL) fail to achieve a complete response (CR) to standard light chain suppressive chemotherapy, and almost all patients eventually experience hematologic relapse and progression of organ involvement. Additional well-tolerated treatment options are needed. We present our retrospective experience of 25 consecutive previously treated AL patients who received daratumumab, a CD38-directed monoclonal antibody approved for the treatment of multiple myeloma. Daratumumab was administered at 16 mg/kg weekly for 8 weeks, then every 2 weeks for 8 doses, and then every 4 weeks. Patients had received a median of 3 prior lines of therapy, with a previous hematologic CR in only 5 patients. The overall hematologic response rate to daratumumab was 76%, including CR in 36% and very good partial response in 24%. Median time to response was 1 month. Therapy was well tolerated, even among the 72% of patients with cardiac AL involvement. Grade 1-2 infusion reactions occurred in 15 patients, but no grade 3 or 4 reactions were observed. Daratumumab is a highly effective agent that produced rapid and deep hematologic responses without unexpected toxicity in our cohort of heavily pretreated AL patients. •Daratumumab is highly active in AL amyloidosis.