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

Eur J Haematol. 2021 Feb;106(2):184-195. doi: 10.1111/ejh.13535. Epub 2020 Nov 9.

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.

Keywords: cardiac amyloidosis; daratumumab; light-chain amyloidosis.

Publication types

  • Multicenter Study
  • Systematic Review

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal / adverse effects
  • Antibodies, Monoclonal / therapeutic use*
  • Antineoplastic Agents, Immunological / administration & dosage
  • Antineoplastic Agents, Immunological / adverse effects
  • Antineoplastic Agents, Immunological / therapeutic use*
  • Biomarkers
  • Clinical Trials as Topic
  • Disease Management
  • Female
  • Humans
  • Immunoglobulin Light-chain Amyloidosis / diagnosis
  • Immunoglobulin Light-chain Amyloidosis / drug therapy*
  • Immunoglobulin Light-chain Amyloidosis / etiology
  • Immunoglobulin Light-chain Amyloidosis / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Recurrence
  • Retrospective Studies
  • Sensitivity and Specificity
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • Biomarkers
  • daratumumab