Subcutaneous daratumumab in Asian patients with heavily pretreated multiple myeloma: subgroup analyses of the noninferiority, phase 3 COLUMBA study

Shinsuke Iida, Takayuki Ishikawa, Chang Ki Min, Kihyun Kim, Su Peng Yeh, Saad Z Usmani, Maria-Victoria Mateos, Hareth Nahi, Christoph Heuck, Xiang Qin, Dolly A Parasrampuria, Katharine S Gries, Ming Qi, Nizar Bahlis, Shigeki Ito, Shinsuke Iida, Takayuki Ishikawa, Chang Ki Min, Kihyun Kim, Su Peng Yeh, Saad Z Usmani, Maria-Victoria Mateos, Hareth Nahi, Christoph Heuck, Xiang Qin, Dolly A Parasrampuria, Katharine S Gries, Ming Qi, Nizar Bahlis, Shigeki Ito

Abstract

The phase 3 COLUMBA study demonstrated noninferiority of subcutaneous daratumumab (DARA SC) to intravenous daratumumab (DARA IV) in relapsed or refractory multiple myeloma. We present a subgroup analysis of Asian patients from COLUMBA. Eligible patients had ≥ 3 prior lines of therapy, including a proteasome inhibitor and an immunomodulatory drug, or were double refractory. Co-primary endpoints were overall response rate (ORR) and maximum trough concentration (Ctrough). Secondary endpoints included rates of infusion-related reactions, progression-free survival, and patient-reported satisfaction with therapy. Sixty-seven Asian patients (DARA SC, n = 30; DARA IV, n = 37) were randomized, including 42 Japanese patients (DARA SC, n = 18; DARA IV, n = 24). Comparable ORRs for DARA SC versus DARA IV were seen in the Asian cohort (66.7% vs 43.2%) and Japanese-only cohort (61.1% vs 54.2%), including patients weighing ≤ 65 kg. Similarity of Ctrough was seen in both Asian and Japanese-only cohorts; the ratio of the geometric mean of the Ctrough concentrations for DARA SC/DARA IV was 143.96% (90% confidence interval (CI), 112.03-185.00%) and 148.02% (90% CI, 113.32-193.34%), respectively. The Asian cohort (both treatment groups) and Japanese-only cohort (DARA SC group) experienced higher rates of grade 3/4 cytopenias compared with the global COLUMBA population, occurring predominantly in patients of low bodyweight; no patients discontinued treatment due to cytopenias. The Cancer Therapy Satisfaction Questionnaire results generally favored DARA SC. In the Asian and Japanese-only cohorts, DARA SC was comparable to DARA IV. The efficacy, pharmacokinetic, safety, and satisfaction results were generally consistent with the global COLUMBA population regardless of patient bodyweight. ClinicalTrials.gov Identifier: NCT03277105.

Keywords: Asian; Daratumumab; Japanese; Monoclonal antibody; Multiple myeloma; Subcutaneous.

Conflict of interest statement

SIida received honoraria and research funding from Janssen, Sanofi, Takeda, Ono, Celgene, Bristol Myers Squibb, and Daiichi Sankyo; and received research funding from Chugai, Kyowa Kirin, AbbVie, and Merck Sharp & Dohme. KK received honoraria from Janssen, Celgene, Takeda, and Amgen; and received a research grant from Celgene and Janssen. SZU served as a consultant or advisor for Amgen, Bristol Myers Squibb, Celgene, Janssen, Merck, SkylineDX, and Takeda; received a research grant from Amgen, Array BioPharma, Bristol Myers Squibb, Celgene, Janssen, Merck, Pharmacyclics, Sanofi, and Takeda; and served on speakers bureaus for Amgen, Celgene, Janssen, Sanofi, and Takeda. M-VM served on an advisory committee for AbbVie, Amgen, Celgene, Genentech, GlaxoSmithKline, Janssen, Mundipharma EDO, PharmaMar, Roche, and Takeda; served on data and monitoring committees for Amgen and Janssen; served on speakers bureaus for Amgen, Celgene, Janssen, and Takeda; received honoraria from Janssen, Celgene, Takeda, Amgen, and Adaptive; and was a member of a board of directors or advisory committee for Janssen, Celgene, Takeda, Amgen, GlaxoSmithKline, AbbVie, Mundipharma EDO, and PharmaMar. CH, XQ, DAP, KSG, and MQ are employed by and own equity in Janssen. NB served as a consultant for and received honoraria from Janssen, Celgene, Amgen, Takeda, and AbbVie. SIto received honoraria from Janssen, Celgene, Bristol Myers Squibb, Ono, and Takeda. TI, CKM, SPY, and HN declare that they have no conflicts of interest.

Figures

Fig. 1
Fig. 1
PFS of (a) Asian patients; (b) Asian patients with baseline bodyweight ≤ 55 kg; and (c) Asian patients with baseline bodyweight ≤ 65 kg. PFS, progression-free survival; DARA, daratumumab; SC, subcutaneous; IV, intravenous; HR, hazard ratio; CI, confidence interval
Fig. 2
Fig. 2
Maximum Ctrough on cycle 3 day 1 of Asian patients by bodyweight subgroups. Ctrough, trough concentration; DARA, daratumumab; IV, intravenous; SC, subcutaneous. The boxes represent the 25th, 50th, and 75th percentiles, and the whiskers represent the furthest values from the median that did not exceed 1.5× interquartile range. Data above or below the respective whisker ends displayed as circles are considered outliers. The diamonds inside each box represent the algorithm mean
Fig. 3
Fig. 3
Mean modified CTSQ scores over time for the satisfaction with therapy domain in Asian patients. CTSQ, Cancer Therapy Satisfaction Questionnaire; SE, standard error; DARA, daratumumab; SC, subcutaneous; IV, intravenous; C, cycle; D, day

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