Daratumumab for relapsed AL amyloidosis—When cumulative real‐world data precedes clinical trials: A multisite study and systematic literature review

Objectives Patients with relapsed/refractory AL amyloidosis (RRAL) have poor prognosis, but emerging data shows promising results with the use daratumumab. We evaluated daratumumab treatment in RRAL in real‐world setting. Methods A retrospective multisite study of RRAL patients treated with daratumumab alone and in combinations. Results Forty‐nine patients, diagnosed between 1.1.2008 and 1.2.2018 were included; 27% also had multiple myeloma (MM). Revised Mayo score was ≥ 3 in 67%. Hematologic overall response rate was 81%, 64% achieved very good partial response (VGPR) or better. Concurrent active MM was associated with lower rates of VGPR (OR 0.19, 95% CI 0.04‐0.81; P = .03) in a multi‐variate analysis. Cardiac and renal responses were 74% and 73%, respectively. Median progression‐free survival (PFS) was 28.4 months and median overall survival (OS) was not reached; 2‐year PFS and OS were 68.6 ± 7.5% and 90.4 ± 4.6%, respectively. Hematologic response correlated with prolonged PFS and OS. Daratumumab was safe and well tolerated, no patients discontinued therapy due to toxicity. Our data was aligned with outcomes from a systematic literature review, which identified 10 case series (n = 517) and 2 clinical trials (n = 62) meeting prespecified criteria. Conclusions Our data support favorable safety tolerability and efficacy of daratumumab among non‐selective RRAL patients in a real‐world setting.