Daratumumab, Bortezomib, and Dexamethasone Versus Bortezomib and Dexamethasone in Chinese Patients with Relapsed or Refractory Multiple Myeloma: Phase 3 LEPUS (MMY3009) Study
Jin Lu, Weijun Fu, Wei Li, Jianda Hu, Gang An, Yafei Wang, Chengcheng Fu, Lijuan Chen, Jie Jin, Xinan Cen, Zheng Ge, Zhen Cai, Ting Niu, Ming Qi, Steven Sun, Xue Gai, Weiping Liu, Wenyu Liu, Xue Yang, Xiaojun Huang, Jin Lu, Weijun Fu, Wei Li, Jianda Hu, Gang An, Yafei Wang, Chengcheng Fu, Lijuan Chen, Jie Jin, Xinan Cen, Zheng Ge, Zhen Cai, Ting Niu, Ming Qi, Steven Sun, Xue Gai, Weiping Liu, Wenyu Liu, Xue Yang, Xiaojun Huang
Abstract
Background: Daratumumab plus bortezomib/dexamethasone (D-Vd) significantly improved outcomes versus Vd in patients with relapsed or refractory multiple myeloma (RRMM) in the phase 3 CASTOR study. We report the results of a prespecified interim analysis of the phase 3 LEPUS study of D-Vd versus Vd in Chinese patients with RRMM.
Patients and methods: Chinese patients with ≥ 1 prior line of therapy were randomized 2:1 to receive 8 cycles (21 days/cycle) of bortezomib (1.3 mg/m2 subcutaneously) and dexamethasone (20 mg orally/intravenously) ± daratumumab (16 mg/kg intravenously). The primary endpoint was progression-free survival (PFS).
Results: A total of 211 patients were randomized (D-Vd, 141; Vd, 70). After an 8.2-month median follow-up, D-Vd significantly prolonged PFS versus Vd (median, not reached vs. 6.3 months; hazard ratio, 0.28; 95% confidence interval, 0.17-0.47; P < .00001) and significantly improved the rates of overall response (83% vs. 65%; P = .00527), ≥ very good partial response (65% vs. 33%; P = .00002), ≥ complete response (33% vs. 11%; P = .00079), and minimal residual disease negativity (10-5 sensitivity; 22% vs. 3%; P = .0002). The PFS benefit of D-Vd versus Vd was maintained across prespecified subgroups, including patients with prior bortezomib treatment and with high-risk cytogenetics. Thrombocytopenia (D-Vd, 51%; Vd, 37%), lymphopenia (44%; 29%), and lung infection (30%; 22%) were the 3 most common grade 3/4 treatment-emergent adverse events. Although patients in both treatment groups experienced higher rates of grade 3/4 lymphopenia and infections versus patients in CASTOR, the safety profile was generally consistent with that of CASTOR.
Conclusion: These data support the use of D-Vd in Chinese patients with RRMM.
Trial registration: ClinicalTrials.gov NCT03234972.
Keywords: Asian; CD38; Efficacy; Monoclonal antibody; Safety.
Conflict of interest statement
Disclosure MQ, SS, XG, and XY are employees of Janssen and own Johnson & Johnson stock. WeipingLiu and WenyuLiu are employees of Janssen. JL, WF, WLi, JH, GA, YW, CF, LC, JJ, XC, ZG, ZC, TN, and XH have no conflicts of interest to disclose. This study (ClinicalTrials.gov Identifier: NCT03234972) was sponsored by Janssen Research & Development, LLC, which provided support for collection, analysis, and interpretation of data; Janssen employee-authors were involved in the decision to submit the article for publication. Medical writing and editorial support were provided by Grace Wang, PharmD, of Cello Health Communications/MedErgy, and were funded by Janssen Global Services, LLC.
Copyright © 2021 Janssen Research & Development, LLC. Published by Elsevier Inc. All rights reserved.
Source: PubMed