A prospective phase 2 trial of daratumumab in patients with previously treated systemic light-chain amyloidosis

Murielle Roussel, Giampaolo Merlini, Sylvie Chevret, Bertrand Arnulf, Anne Marie Stoppa, Aurore Perrot, Giovanni Palladini, Lionel Karlin, Bruno Royer, Antoine Huart, Margaret Macro, Pierre Morel, Laurent Frenzel, Cyrille Touzeau, Eileen Boyle, Véronique Dorvaux, Fabien Le Bras, David Lavergne, Frank Bridoux, Arnaud Jaccard

Research output: Contribution to journalArticlepeer-review


Daratumumab is a human monoclonal antibody targeting CD38, an antigen uniformly expressed by plasma cells in multiple myeloma and light-chain amyloidosis (AL). We report the results of a prospective multicenter phase 2 study of daratumumab monotherapy in AL (NCT02816476). Forty previously treated AL patients with a difference between involved and uninvolved free light chains (dFLC) >50 mg/L were included in 15 centers between September of 2016 and April of 2018. Patients received 6 28-day cycles of IV daratumumab, every week for cycles 1 and 2 and every 2 weeks for cycles 3 through 6. Median age was 69 years (range, 45-83). Twenty-six patients had ≥2 organs involved, with heart in 24 and kidney in 26. Median time from diagnosis to enrollment was 23 months (interquartile range, 4-122), with a median of 3 prior therapies (range, 1-5). At data cutoff (September of 2019), all patients discontinued therapy; 33 received the planned 6 cycles. Overall, 22 patients had hematological response, and 19 patients (47.5%) achieved very good partial response (dFLC <40 mg/L) or better. Median time to hematological response was 1 week. Patients with no response after 4 doses were unlikely to respond further. Renal and cardiac responses occurred in 8 and 7 patients, respectively. Daratumumab was well tolerated, with no unexpected adverse events. With a median follow-up of 26 months, the 2-year overall survival rate was 74% (95% confidence interval, 62-81). Daratumumab monotherapy is associated with deep and rapid hematological responses in previously treated AL patients, with a good safety profile. Further studies of daratumumab in combination regimens are warranted.

Original languageEnglish
Pages (from-to)1531-1540
Number of pages10
Issue number18
Publication statusPublished - Apr 30 2020


  • Aged
  • Antibodies, Monoclonal/administration & dosage
  • Biomarkers
  • Combined Modality Therapy
  • Female
  • Humans
  • Immunoglobulin Light-chain Amyloidosis/diagnosis
  • Male
  • Middle Aged
  • Prognosis
  • Retreatment
  • Severity of Illness Index
  • Treatment Outcome


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