Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone With Minimal Residual Disease Response-Adapted Therapy in Newly Diagnosed Multiple Myeloma

Luciano J. Costa, Saurabh Chhabra, Eva Medvedova, Bhagirathbhai R. Dholaria, Timothy M. Schmidt, Kelly N. Godby, Rebecca Silbermann, Binod Dhakal, Susan Bal, Smith Giri, Anita D'Souza, Aric Hall, Pamela Hardwick, James Omel, Robert F. Cornell, Parameswaran Hari, Natalie S. Callander

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

PURPOSEThe MASTER trial combined daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) in newly diagnosed multiple myeloma (NDMM), using minimal residual disease (MRD) by next-generation sequencing (NGS) to inform the use and duration of Dara-KRd post-autologous hematopoietic cell transplantation (AHCT) and treatment cessation in patients with two consecutive MRD-negative assessments.METHODSThis multicenter, single-arm, phase II trial enrolled patients with NDMM with planed enrichment for high-risk cytogenetic abnormalities (HRCAs). Patients received Dara-KRd induction, AHCT, and Dara-KRd consolidation, according to MRD status. MRD was evaluated by NGS at the end of induction, post-AHCT, and every four cycles (maximum of eight cycles) of consolidation. Primary end point was achievement of MRD negativity (< 10-5). Patients with two consecutive MRD-negative assessments entered treatment-free MRD surveillance.RESULTSAmong 123 participants, 43% had none, 37% had 1, and 20% had 2+ HRCA. Median age was 60 years (range, 36-79 years), and 96% had MRD trackable by NGS. Median follow-up was 25.1 months. Overall, 80% of patients reached MRD negativity (78%, 82%, and 79% for patients with 0, 1, and 2+ HRCA, respectively), 66% reached MRD < 10-6, and 71% reached two consecutive MRD-negative assessments during therapy, entering treatment-free surveillance. Two-year progression-free survival was 87% (91%, 97%, and 58% for patients with 0, 1, and 2+ HRCA, respectively). Cumulative incidence of MRD resurgence or progression 12 months after cessation of therapy was 4%, 0%, and 27% for patients with 0, 1, or 2+ HRCA, respectively. Most common serious adverse events were pneumonia (6%) and venous thromboembolism (3%).CONCLUSIONDara-KRd, AHCT, and MRD response-adapted consolidation leads to high rate of MRD negativity in NDMM. For patients with 0 or 1 HRCA, this strategy creates the opportunity of MRD surveillance as an alternative to indefinite maintenance.

Original languageEnglish (US)
Pages (from-to)2901-2912
Number of pages12
JournalJournal of Clinical Oncology
Volume40
Issue number25
DOIs
StatePublished - Sep 1 2022

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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