Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis.
Systemic immunoglobulin light-chain (AL) amyloidosis is characterized by deposition of amyloid fibrils of light chains produced by clonal CD38+ plasma cells. Daratumumab, a human CD38-targeting antibody, may improve outcomes for this disease.We randomly assigned patients with newly diagnosed AL amyloidosis to receive six cycles of bortezomib, cyclophosphamide, and dexamethasone either alone (control group) or with subcutaneous daratumumab followed by single-agent daratumumab every 4 weeks for up to 24 cycles (daratumumab group). The primary end point was a hematologic complete response.A total of 388 patients underwent randomization. The median follow-up was 11.4 months. The percentage of patients who had a hematologic complete response was significantly higher in the daratumumab group than in the control group (53.3% vs. 18.1%) (relative risk ratio, 2.9; 95% confidence interval [CI], 2.1 to 4.1; P<0.001). Survival free from major organ deterioration or hematologic progression favored the daratumumab group (hazard ratio for major organ deterioration, hematologic progression, or death, 0.58; 95% CI, 0.36 to 0.93; P = 0.02). At 6 months, more cardiac and renal responses occurred in the daratumumab group than in the control group (41.5% vs. 22.2% and 53.0% vs. 23.9%, respectively). The four most common grade 3 or 4 adverse events were lymphopenia (13.0% in the daratumumab group and 10.1% in the control group), pneumonia (7.8% and 4.3%, respectively), cardiac failure (6.2% and 4.8%), and diarrhea (5.7% and 3.7%). Systemic administration-related reactions to daratumumab occurred in 7.3% of the patients. A total of 56 patients died (27 in the daratumumab group and 29 in the control group), most due to amyloidosis-related cardiomyopathy.Among patients with newly diagnosed AL amyloidosis, the addition of daratumumab to bortezomib, cyclophosphamide, and dexamethasone was associated with higher frequencies of hematologic complete response and survival free from major organ deterioration or hematologic progression. (Funded by Janssen Research and Development; ANDROMEDA ClinicalTrials.gov number, NCT03201965.).
Authors: Efstathios Kastritis, Giovanni Palladini, Monique C Minnema, Ashutosh D Wechalekar, Arnaud Jaccard, Hans C Lee, Vaishali Sanchorawala, Simon Gibbs, Peter Mollee, Christopher P Venner, Jin Lu, Stefan Schönland, Moshe E Gatt, Kenshi Suzuki, Kihyun Kim, M Teresa Cibeira, Meral Beksac, Edward Libby, Jason Valent, Vania Hungria, Sandy W Wong, Michael Rosenzweig, Naresh Bumma, Antoine Huart, Meletios A Dimopoulos, Divaya Bhutani, Adam J Waxman, Stacey A Goodman, Jeffrey A Zonder, Selay Lam, Kevin Song, Timon Hansen, Salomon Manier, Wilfried Roeloffzen, Krzysztof Jamroziak, Fiona Kwok, Chihiro Shimazaki, Jin-Seok Kim, Edvan Crusoe, Tahamtan Ahmadi, NamPhuong Tran, Xiang Qin, Sandra Y Vasey, Brenda Tromp, Jordan M Schecter, Brendan M Weiss, Sen H Zhuang, Jessica Vermeulen, Giampaolo Merlini, Raymond L Comenzo, ANDROMEDA Trial Investigators