Daratumumab for relapsed AL amyloidosis—When cumulative real‐world data precedes clinical trials: A multisite study and systematic literature review
Tamir Shragai, Moshe E. Gatt, Noa Lavie, Iuliana Vaxman, Tamar Tadmor, Ory Rouvio, Miri Zektser, Nethanel A. Horowitz, Hila Magen, Mouna Ballan, Celia Suru, Efrat Luttwak, Shai Levi, Tomer Ziv‐Baran, Irit Avivi, Yaël C. Cohen
Abstract
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.