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

Abstract

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.

Keywords: Asian; Body weight; Daratumumab; Efficacy; Light-chain amyloidosis; Safety.

Conflict of interest statement

KS consulted for and received honoraria and research funding from Celgene and Amgen; consulted for and received honoraria from Takeda and Janssen; received honoraria and research funding from Bristol Myers Squibb; and received honoraria from Ono, Novartis, Sanofi, and AbbVie. ADW received honoraria from and served on a board of directors or advisory committees for Janssen, Takeda, Caelum, and Celgene. KK consulted for and received honoraria and research funding from Bristol Myers Squibb, Takeda, Amgen, Celgene, and Janssen. CS received honoraria from Sanofi, Bristol Myers Squibb, and Janssen. FZ is currently employed by Peking University First Hospital. SI received honoraria and research funding from Sanofi, Bristol Myers Squibb, Daiichi Sankyo, Takeda, Ono, Celgene, and Janssen; and received research funding from Merck, AbbVie, Kyowa Kirin, and Chugai. NK received honoraria from Janssen. NT, SYV, and BT are current employees of Janssen and hold equity in Johnson & Johnson. XQ is a current employee of Janssen. BMW was an employee of Janssen at the time of the study. RLC consulted for and received research funding from Prothena, Janssen, Takeda, and Karyopharm and consulted for Amgen, Sanofi, Unum, and Caelum. EK consulted for and received honoraria and research funding from Janssen and Amgen; consulted for and received honoraria from Genesis and Takeda; was reimbursed by Janssen, Genesis, and Takeda for travel, accommodations, and expenses; and consulted for Pfizer. JSK, TI, C-KM, ZC, XC, TF, H-JS, and JL had no relevant conflicts of interest to disclose.

© 2023. The Author(s).

Figures

Fig. 1

MOD-PFSa,b of a the global ITT population and b the Asian cohort. MOD-PFS, major organ deterioration progression-free survival; ITT, intent-to-treat; D-VCd, daratumumab subcutaneous plus bortezomib/cyclophosphamide/dexamethasone; VCd, bortezomib/cyclophosphamide/dexamethasone; NE, not estimable; HR, hazard ratio; CI, confidence interval; IPCW, inverse probability of censoring weighting. aBecause of the small number of Asian patients, an IPCW analysis method was not applicable to analyze MOD-PFS, and MOD-PFS was based on independent review committee assessment after adjusting for dependent censoring due to subsequent non-cross-resistant anti-plasma cell therapy. MOD-PFS was defined as the time from randomization to any of the following events (whichever occurred first): death, clinical manifestation of cardiac or renal failure, or hematologic progression. bEvaluated in the ITT population, which included all randomized patients

Fig. 2

MOD-EFSa,b of a the global ITT population and b the Asian cohort. MOD-EFS, major organ deterioration event-free survival; ITT, intent-to-treat; D-VCd, daratumumab subcutaneous plus bortezomib/cyclophosphamide/dexamethasone; VCd, bortezomib/cyclophosphamide/dexamethasone; NE, not estimable; HR, hazard ratio; CI, confidence interval; IPCW, inverse probability of censoring weighting. aBecause of the small number of Asian patients, an IPCW analysis method was not applicable to analyze MOD-EFS, and MOD-EFS was based on independent review committee assessment after adjusting for dependent censoring due to subsequent non-cross-resistant anti-plasma cell therapy. MOD-EFS was defined as hematologic progression, end-stage cardiac or renal disease, initiation of subsequent non-cross-resistant anti-plasma cell therapy, or death, whichever came first. bEvaluated in the ITT population, which included all randomized patients