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

Author(s): Luciano J. Costa, MD, PhD1,2;Saurabh Chhabra, MD3;Eva Medvedova, MD4;Bhagirathbhai R. Dholaria, MD5;Timothy M. Schmidt, MD6;Kelly N. Godby, MD1,2;Rebecca Silbermann, MD4;Binod Dhakal, MD3;Susan Bal, MD1,2;Smith Giri, MD1,2;Anita D’Souza, MD3;Aric Hall, MD6;Pamela Hardwick, RN2;James Omel, MD7;Robert F. Cornell, MD5;Parameswaran Hari, MD3;and Natalie S. Callander, MD6
Source: DOI: 10.1200/JCO.21.01935
Lucio Gordan MD

Very interesting study with potential practical use of MRD surveillance instead of expensive maintenance therapies with toxicities for patients with lower risk disease from a genomic standpoint. Larger studies may be needed to confirm this strategy.


The 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.


This 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.


Among 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%).


Dara-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.

Author Affiliations

1Division of Hematology/Oncology, University of Alabama at Birmingham, Birmingham, AL;2O’Neal Comprehensive Cancer Center at University of Alabama at Birmingham, Birmingham, AL;3Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI;4Oregon Health & Science University, Portland, OR;5Department of Medicine, Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN;6University of Wisconsin, Madison, WI;7Independent Patient Advocate, Omaha, NE

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