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Clinical Trial
. 2020 Aug 20;13(1):115.
doi: 10.1186/s13045-020-00948-5.

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk

Katja Weisel  1 , Andrew Spencer  2 , Suzanne Lentzsch  3 , Hervé Avet-Loiseau  4 , Tomer M Mark  5 , Ivan Spicka  6 , Tamas Masszi  7 , Birgitta Lauri  8 , Mark-David Levin  9 , Alberto Bosi  10 , Vania Hungria  11 , Michele Cavo  12 , Je-Jung Lee  13 , Ajay Nooka  14 , Hang Quach  15 , Markus Munder  16 , Cindy Lee  17 , Wolney Barreto  18 , Paolo Corradini  19 , Chang-Ki Min  20 , Asher A Chanan-Khan  21 , Noemi Horvath  17 , Marcelo Capra  22 , Meral Beksac  23 , Roberto Ovilla  24 , Jae-Cheol Jo  25 , Ho-Jin Shin  26 , Pieter Sonneveld  27 , Tineke Casneuf  28 , Nikki DeAngelis  29 , Himal Amin  30 , Jon Ukropec  31 , Rachel Kobos  30 , Maria-Victoria Mateos  32
Affiliations
Clinical Trial

Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk

Katja Weisel et al. J Hematol Oncol. .

Abstract

Background: Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM).

Methods: This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10-5 sensitivity threshold) was assessed via the clonoSEQ® assay V2.0. Of the 498 patients randomized, 40 (16%) in the D-Vd group and 35 (14%) in the Vd group were categorized as high risk.

Results: After a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR.

Conclusion: These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status.

Trial registration: ClinicalTrials.gov, NCT02136134 . Registered 12 May 2014.

Keywords: Clinical trials; Multiple myeloma; Myeloma therapy.

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Conflict of interest statement

KW received honoraria from GlaxoSmithKline, Sanofi, Adaptive, Amgen, Bristol-Myers Squibb, Celgene, Janssen, and Takeda; served in a consulting or advisory role for GlaxoSmithKline, Amgen, Adaptive, Bristol-Myers Squibb, Celgene, Janssen, Takeda, Sanofi, and Juno; and received institutional research funding from Amgen, Celgene, Sanofi, and Janssen. AS received honoraria from Celgene, Janssen, Amgen, AbbVie, Servier, and Takeda; served in a consulting or advisory role for Celgene, Janssen, Servier, and AbbVie; and served on a speakers bureau for and received institutional funding from Janssen, Takeda, and Celgene. SL holds stock and patents, royalties, or other intellectual property from Caelum Biosciences; served in a consulting or advisory role for Caelum Biosciences, Takeda, Janssen, Celgene, Bristol-Myers Squibb, AbbVie, and Bayer; received research funding from Sanofi; declared another relationship with Clinical Care Options; and served on data safety monitoring boards for Sorrento and Bayer. TMM holds stock in AbbVie; received honoraria and research funding from Celgene; and served in a consulting or advisory role for Janssen, Takeda, and Adaptive. M-DL is a consultant for and receives honoraria and travel support from AbbVie, Celgene, Amgen, and Janssen. AB received honoraria from Amgen; served in a consulting or advisory role for Takeda; and had travel, accommodations, or other expenses paid or reimbursed by Celgene, Janssen, and Amgen. VH served in a consulting or advisory role and on a speakers bureau for AbbVie, Amgen, Celgene, Janssen, Takeda, and Bristol-Myers Squibb. MCavo received honoraria from Celgene, Janssen, Amgen, Bristol-Myers Squibb, AbbVie, and Takeda; served in a consulting or advisory role for Janssen, Celgene, Amgen, and AbbVie; and served on a speakers bureau for and had travel, accommodations, or other expenses paid or reimbursed by Janssen and Celgene. AN received honoraria from and served in a consulting or advisory role for Janssen, GlaxoSmithKline, Celgene, Amgen, Takeda, Spectrum, Bristol-Myers Squibb, Karyopharm, Oncopeptides, and Adaptive and received research funding from Janssen, GlaxoSmithKline, Celgene, Amgen, Takeda, Karyopharm, and Bristol-Myers Squibb. HQ served in a consulting or advisory role for Celgene, Amgen, Karyopharm, and GlaxoSmithKline and received research funding from Celgene and Amgen. MM received honoraria from Janssen, Bristol-Myers Squibb, Celgene, and Amgen; served in a consulting or advisory role for Janssen, Bristol-Myers Squibb, Takeda, Celgene, Amgen, and Heidelberg Pharma; received research funding from Incyte and Bristol-Myers Squibb; and had travel, accommodations, or other expenses paid or reimbursed by Janssen, Bristol-Myers Squibb, Takeda, Celgene, and Amgen. CL received honoraria from and consulted for Amgen, Janssen-Cilag, Takeda, and Celgene. PC received honoraria from Daiichi Sankyo, Kite, KiowaKirin, Celgene, Janssen, Novartis, Roche, Takeda, Sanofi, Amgen, Gilead, and AbbVie and had travel, accommodations, or other expenses paid or reimbursed by Novartis, Janssen, Celgene, Bristol-Myers Squibb, Takeda, Gilead, Amgen, and AbbVie. AAC-K received research funding from the Mayo Clinic. NH served on the board of directors or advisory committees for Janssen. MCapra received honoraria from AbbVie, GlaxoSmithKline, Bristol-Myers Squibb, Adaptive, Takeda, Janssen, and Celgene. MB served in a consulting or advisory role and on a speakers bureau for Amgen, Janssen, and Takeda. RO consulted for Janssen. PS received honoraria from and research funding from Amgen, Celgene, Janssen, SkylineDx, and Takeda. TC is an employee of Janssen and holds stock options from Johnson & Johnson. ND, HA, JU, and RK are employees of Janssen. M-VM received honoraria from and served in a consulting or advisory role for Janssen, Celgene, Amgen, Takeda, GlaxoSmithKline, AbbVie, Seattle Genetics, and Adaptive. HA-L, IS, TM, BL, J-JL, WB, C-KM, J-CJ, and H-JS have no conflicts of interest to disclose.

Figures

Fig. 1
Fig. 1
PFS based on cytogenetic risk status. PFS in the ITT/biomarker risk population (patients in the ITT population who met the biomarker criteria for risk assessment): a standard cytogenetic risk patients and b high cytogenetic risk patients. PFS in patients with 1 prior line of therapy: c standard cytogenetic risk patients and d high cytogenetic risk patients. CI, confidence interval; D-Vd, daratumumab plus bortezomib/dexamethasone; HR, hazard ratio; ITT intent-to-treat; PFS, progression-free survival; Vd, bortezomib/dexamethasone
Fig. 2
Fig. 2
PFS2 based on cytogenetic risk status. PFS2 in the ITT/biomarker risk population (patients in the ITT population who met the biomarker criteria for risk assessment): a standard cytogenetic risk patients and b high cytogenetic risk patients. PFS2 in patients with 1 prior line of therapy: c standard cytogenetic risk patients and d high cytogenetic risk patients. CI, confidence interval; D-Vd, daratumumab plus bortezomib/dexamethasone; HR, hazard ratio; ITT intent-to-treat; PFS2, progression-free survival on the subsequent line of therapy; Vd, bortezomib/dexamethasone
See this image and copyright information in PMC

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