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

Dr. Gordan's Thoughts

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.

PURPOSE

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.

METHODS

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.

RESULTS

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%).

CONCLUSION

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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