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

Katja Weisel, Andrew Spencer, Suzanne Lentzsch, Hervé Avet-Loiseau, Tomer M. Mark, Ivan Spicka, Tamas Masszi, Birgitta Lauri, Mark David Levin, Alberto Bosi, Vania Hungria, Michele Cavo, Je Jung Lee, Ajay Nooka, Hang Quach, Markus Munder, Cindy Lee, Wolney Barreto, Paolo Corradini, Chang Ki MinAsher A. Chanan-Khan, Noemi Horvath, Marcelo Capra, Meral Beksac, Roberto Ovilla, Jae Cheol Jo, Ho Jin Shin, Pieter Sonneveld, Tineke Casneuf, Nikki Deangelis, Himal Amin, Jon Ukropec, Rachel Kobos, Maria Victoria Mateos

Research output: Contribution to journalArticlepeer-review

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

Original languageEnglish (US)
Article number115
JournalJournal of Hematology and Oncology
Volume13
Issue number1
DOIs
StatePublished - Aug 20 2020

Keywords

  • Clinical trials
  • Multiple myeloma
  • Myeloma therapy

ASJC Scopus subject areas

  • Hematology
  • Molecular Biology
  • Oncology
  • Cancer Research

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