Daratumumab for relapsed or refractory AL amyloidosis with high plasma cell burden

Hematol Oncol. 2019 Dec;37(5):595-600. doi: 10.1002/hon.2677. Epub 2019 Nov 6.

Abstract

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) are limited. We report retrospective data of 10 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 noninvolved 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, eight (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.

Keywords: AL; amyloidosis; daratumumab; light chain; organ; plasma cell; response.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • 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*
  • Bone Marrow / metabolism
  • Bone Marrow / pathology
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Immunoglobulin Light-chain Amyloidosis / diagnosis*
  • Immunoglobulin Light-chain Amyloidosis / drug therapy*
  • Immunoglobulin Light-chain Amyloidosis / mortality
  • Infections / etiology
  • Infections / therapy
  • Lymphocyte Count*
  • Male
  • Middle Aged
  • Plasma Cells / pathology*
  • Recurrence
  • Retreatment
  • Severity of Illness Index
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents, Immunological
  • daratumumab

Grants and funding