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MRD Response–Adapted Therapy in Patients Receiving Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone Plus AHCT for Newly Diagnosed Multiple Myeloma


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In the phase II MASTER trial reported in the Journal of Clinical Oncology, Luciano J. Costa, MD, PhD, and colleagues found that daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) induction; autologous hematopoietic cell transplantation (AHCT); and measurable residual disease (MRD) response–adapted Dara-KRd consolidation produced high rates of MRD negativity in newly diagnosed patients with multiple myeloma. The findings suggest that MRD surveillance may be appropriate for many patients with fewer high-risk cytogenetic abnormalities.

Study Details

The study included 123 patients enrolled at five U.S. sites between March 2018 and October 2020. Patients were to receive four cycles of Dara-KRd induction, AHCT, and up to two phases of Dara-KRd consolidation of four cycles each (cycles 5–8 and 9–12). MRD status was assessed by next-generation sequencing at end of induction, post-AHCT, and after every four cycles of consolidation.

The primary endpoint was achievement of MRD negativity (< 10−5). Patients with two consecutive MRD-negative assessments began treatment-free MRD surveillance. The study population was planned to be enriched for high-risk cytogenetic abnormalities; overall, 53 patients (43%) had no high-risk cytogenetic abnormality, 46 (37%) had one, and 24 (20%) had more than one.

Luciano J. Costa, MD, PhD

Luciano J. Costa, MD, PhD

Key Findings

Median age was 60 years (range = 36–79 years). Overall, 118 patients (96%) had MRD assessable by next-generation sequencing. Median follow-up was 25.1 months.

As best response, 80% of patients achieved MRD negativity, including 78%, 82%, and 79% with no, one, and more than one high-risk cytogenetic abnormality, respectively. A total of 66% achieved MRD < 10−6.

A total of 84 patients (71%) had two consecutive MRD-negative assessments and began treatment-free MRD surveillance; of these, 33 (of 53), 36 (of 46), and 15 (of 24) had no, one, and more than one high-risk cytogenetic abnormality. Median follow-up after treatment cessation was 14.2 months.

The cumulative incidence of disease progression or MRD resurgence at 12 months was 6.4%, including 4%, 0%, and 27% among patients with no, one, and more than one high-risk cytogenetic abnormality. Progression-free survival at 2 years was 87% among all patients, including rates of 91%, 97%, and 58% among patients with no, one, and more than one high-risk cytogenetic abnormality.

Grade ≥ 3 adverse events occurred in 74% of patients, most commonly hematologic events (neutropenia in 35% and lymphopenia in 22%); the most common nonhematologic events were hypertension (10%) and fatigue (9%). Serious adverse events occurred in 18%, most commonly pneumonia (6%) and venous thromboembolism (3%).

The investigators concluded, “Dara-KRd, AHCT, and MRD response–adapted consolidation leads to [a] high rate of MRD negativity in newly diagnosed multiple myeloma. For patients with no or one high-risk cytogenetic abnormality, this strategy creates the opportunity of MRD surveillance as an alternative to indefinite maintenance.”

Dr. Costa, of the Division of Hematology and Oncology, University of Alabama at Birmingham, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was supported by Amgen and Janssen. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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