MRD-driven phase 2 study of daratumumab, carfilzomib, lenalidomide, and dexamethasone in newly diagnosed multiple myeloma

Manisha Bhutani ¹, Myra Robinson ², David Foureau ³

⁰Department of Hematologic Oncology and Blood Disorders, Atrium Health Levine Cancer Institute, Wake Forest University School of Medicine, Charlotte, NC.

Blood Advances +

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November 22, 2024

View abstract on PubMed

Summary

Newly diagnosed multiple myeloma patients treated with Dara-KRd achieved high response rates and measurable residual disease negativity. An MRD-adapted strategy improved outcomes for MRD-positive patients and maintained durable MRD control in MRD-negative patients.

Area Of Science

Hematology
Clinical Oncology
Immunology

Background

Measurable residual disease (MRD) status is a key prognostic factor in newly diagnosed multiple myeloma (NDMM).
The role of MRD in guiding treatment decisions for NDMM remains under investigation.
Daratumumab, carfilzomib, lenalidomide, and dexamethasone (Dara-KRd) is a potential induction regimen for NDMM.

Purpose Of The Study

To assess the efficacy and safety of Dara-KRd induction followed by an MRD-adapted strategy in NDMM.
To evaluate complete response (CR) and stringent CR (≥CR) rates post-induction.
To determine the impact of MRD status on treatment adaptation and long-term outcomes.

Main Methods

A Phase 2 clinical trial involving 39 NDMM patients.
Induction therapy with Dara-KRd followed by an MRD-tailored strategy based on next-generation sequencing.
Flow cytometry analysis of T cells to assess immune response.
Stratification into MRD-negative maintenance (Group A), MRD-positive transplant-eligible (Group B), and MRD-positive transplant-ineligible (Group C) groups.

Main Results

54% of patients achieved ≥CR after Dara-KRd induction, with MRD-negative rates of 59% (10⁻⁵) and 41% (10⁻⁶).
MRD-negative patients maintained sustained MRD negativity with lenalidomide maintenance (77.8%).
MRD-positive patients converted to MRD-negative post-transplant (62.5%) or consolidation (77%), with no new safety concerns for Dara-KRd.

Conclusions

Dara-KRd induction in NDMM yields high response and MRD-negative rates, with a favorable safety profile.
An MRD-adapted strategy effectively deepens responses in MRD-positive patients and sustains MRD control in MRD-negative patients.
Dara-KRd promotes T-cell activation, correlating with MRD-negative status post-induction.