Daratumumab plus bortezomib, cyclophosphamide, and dexamethasone in Asian patients with newly diagnosed AL amyloidosis: subgroup analysis of ANDROMEDA

• Published in: Annals of hematology Vol. 102; no. 4; pp. 863 - 876
• Main Authors: Suzuki, Kenshi, Wechalekar, Ashutosh D., Kim, Kihyun, Shimazaki, Chihiro, Kim, Jin Seok, Ikezoe, Takayuki, Min, Chang-Ki, Zhou, Fude, Cai, Zhen, Chen, Xiaonong, Iida, Shinsuke, Katoh, Nagaaki, Fujisaki, Tomoaki, Shin, Ho-Jin, Tran, NamPhuong, Qin, Xiang, Vasey, Sandra Y., Tromp, Brenda, Weiss, Brendan M., Comenzo, Raymond L., Kastritis, Efstathios, Lu, Jin
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.04.2023; Springer Nature B.V
• Subjects: Amyloidosis; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Bortezomib - adverse effects; Cyclophosphamide - adverse effects; Dexamethasone - adverse effects; Hematology; Hepatitis B; Humans; Immunoglobulin Light-chain Amyloidosis - drug therapy; Immunoglobulin Light-chain Amyloidosis - etiology; Immunotherapy; Inhibitor drugs; Medicine; Medicine & Public Health; Multiple Myeloma - drug therapy; Oncology; Original; Original Article; Steroids; Efficacy; Safety; Light-chain amyloidosis; Asian; Daratumumab; Body weight
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-023-05090-z

Subcutaneous daratumumab plus bortezomib/cyclophosphamide/dexamethasone (VCd; D-VCd) improved outcomes versus VCd for patients with newly diagnosed immunoglobulin light-chain (AL) amyloidosis in the phase 3 ANDROMEDA study. We report a subgroup analysis of Asian patients (Japan; Korea; China) from ANDROMEDA. Among 388 randomized patients, 60 were Asian (D-VCd, n  = 29; VCd, n  = 31). At a median follow-up of 11.4 months, the overall hematologic complete response rate was higher for D-VCd versus VCd (58.6% vs. 9.7%; odds ratio, 13.2; 95% confidence interval [CI], 3.3–53.7; P  < 0.0001). Six-month cardiac and renal response rates were higher with D-VCd versus VCd (cardiac, 46.7% vs. 4.8%; P  = 0.0036; renal, 57.1% vs. 37.5%; P  = 0.4684). Major organ deterioration progression-free survival (MOD-PFS) and major organ deterioration event-free survival (MOD-EFS) were improved with D-VCd versus VCd (MOD-PFS: hazard ratio [HR], 0.21; 95% CI, 0.06–0.75; P  = 0.0079; MOD-EFS: HR, 0.16; 95% CI, 0.05–0.54; P  = 0.0007). Twelve deaths occurred (D-VCd, n  = 3; VCd, n  = 9). Twenty-two patients had baseline serologies indicating prior hepatitis B virus (HBV) exposure; no patient experienced HBV reactivation. Although grade 3/4 cytopenia rates were higher than in the global safety population, the safety profile of D-VCd in Asian patients was generally consistent with the global study population, regardless of body weight. These results support D-VCd use in Asian patients with newly diagnosed AL amyloidosis. ClinicalTrials.gov Identifier: NCT03201965.