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    Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)

    Category: Treatment of Newly Diagnosed Myeloma (excluding t-cell redirection therapy)

    Real-World Evaluation of Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (D-VRd) Induction Followed by Daratumumab and Lenalidomide (DR) Maintenance in Transplant-Eligible Multiple Myeloma

    (PA-437) Real-World Evaluation of Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone (D-VRd) Induction Followed by Daratumumab and Lenalidomide (DR) Maintenance in Transplant-Eligible Multiple Myeloma

    Friday, September 19, 2025
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    Introduction:      The introduction of novel therapeutic agents has significantly improved outcomes in multiple myeloma (MM). The phase 2 GRIFFIN and phase 3 PERSEUS trials demonstrated that adding daratumumab to VRd induction and consolidation, as well as to lenalidomide maintenance, significantly enhances response depth and prolongs progression-free survival. However, long-term real-world follow-up data on this regimen remain limited. This study evaluates the real-world experience of D-VRd induction followed by autologous stem cell transplantation (ASCT) and daratumumab plus lenalidomide (DR) maintenance as frontline therapy for transplant-eligible newly diagnosed multiple myeloma (TE-NDMM) patients.

    Methods:   We conducted a retrospective analysis of TE-NDMM patients who received D-VRd induction between January 2021 and March 2025. Patient demographics, disease characteristics, response rates, and clinical outcomes were assessed using descriptive statistics. A swimmer plot was utilized to visualize treatment timelines, duration, and response evolution.

    Results:   A total of 22 patients received D-VRd induction between April 2021 and February 2025. The median age was 60 years (range, 36-73), with 59% female, 72% White, and 28% Black. At diagnosis, 45% had an ECOG performance status of 0–1, and ISS staging was I in 59%, II in 27%, and III in 14%. Clinical characteristics included hemoglobin < 10 g/dL in 40%, lytic bone lesions in 77%, and creatinine >2 mg/dL in 5%. The IgG isotype was present in 82%. Cytogenetic data were available for five patients. At a median follow-up of 26 months (range, 9–45), 17 patients had undergone ASCT. The overall response rate (ORR) was 100%, with 76% achieving a complete response (CR) or better, 18% a very good partial response (VGPR), and 6% a partial response (PR). No cases of primary refractory disease, progression, or relapse were observed. One patient in CR died from COVID-19. Among the 94% of patients who initiated DR maintenance, one discontinued daratumumab due to a skin reaction, and two discontinued lenalidomide due to diarrhea and neutropenia. Post-ASCT, the ORR remained 100%, with CR in 30%, VGPR in 53%, and PR in 17%. Responses deepened during maintenance: 78% of patients with VGPR post-ASCT converted to CR, while among those with PR post-ASCT, 33% improved to CR and 33% to VGPR.

    Conclusions:   D-VRd induction followed by DR maintenance demonstrated high efficacy in this real-world cohort, with an ORR of 100% and 94% of patients achieving VGPR or better. These findings reinforce the effectiveness of this regimen as a frontline option for TE-NDMM patients and support its broader implementation in clinical practice.