A new study is offering further evidence that a four-drug combination including daratumumab is significantly improving outcomes for patients with newly diagnosed multiple myeloma, particularly those ineligible for or deferring stem cell transplantation. The research, published in the New England Journal of Medicine, highlights the benefits of adding daratumumab to a standard treatment regimen of bortezomib, lenalidomide, and dexamethasone (VRd).
Multiple myeloma, a cancer of plasma cells, remains a challenging disease to treat. Recent advancements, however, have focused on incorporating targeted therapies like daratumumab, a monoclonal antibody, into treatment protocols. This latest research builds on previous findings demonstrating improved survival rates with daratumumab-based regimens, and specifically examines the impact of combining it with VRd in patients who may not be candidates for, or are delaying, a stem cell transplant. The goal is to achieve deeper and more durable responses, ultimately extending progression-free survival for these individuals.
D-VRd Demonstrates Superior Minimal Residual Disease Negativity
The phase 3 trial involved 395 patients with transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma. Participants were randomly assigned to receive either eight cycles of daratumumab plus VRd (D-VRd) or VRd alone, followed by D-Rd or Rd until disease progression. The primary endpoint of the study was the rate of minimal residual disease (MRD) negativity – meaning no detectable cancer cells remaining – at a level of 10-5, assessed using next-generation sequencing. Results showed a significantly higher MRD-negativity rate of 60.9% in the D-VRd group compared to 39.4% in the VRd group (odds ratio, 2.37; 95% confidence interval, 1.58–3.55; P < 0.0001).
Beyond MRD negativity, the D-VRd combination similarly led to significantly higher rates of complete response or better (≥CR), with 81.2% of patients achieving this milestone compared to 61.6% in the VRd group (P < 0.0001). Sustained MRD negativity, defined as remaining negative for at least 12 months, was also notably improved with D-VRd (48.7% versus 26.3%; P < 0.0001). These deeper responses translated into a 43% lower risk of disease progression or death for patients receiving D-VRd (hazard ratio, 0.57; 95% confidence interval, 0.41–0.79; P = 0.0005).
Safety Profile Consistent with Known Treatments
Researchers reported that adverse events observed in the trial were consistent with the known safety profiles of both daratumumab and VRd. This suggests that the addition of daratumumab to the VRd regimen does not introduce significantly new or unexpected safety concerns. The FDA approved daratumumab and hyaluronidase-fihj (Darzalex Faspro) in November 2025 for adults with high-risk smoldering multiple myeloma, further expanding its use in the treatment landscape according to the FDA.
Adding daratumumab to standard VRD treatment has been shown to help people with newly diagnosed multiple myeloma live longer without their cancer getting worse or dying. After a median of 4 years, 84% of those who received daratumumab plus the standard treatment and 68% of patients who received the standard treatment—which included bortezomib, lenalidomide, and dexamethasone—were alive and free of cancer progression as reported by the National Cancer Institute.
Implications for Future Treatment Strategies
The findings of this trial strongly support the use of D-VRd quadruplet therapy as a new standard of care for transplant-ineligible or transplant-deferred newly diagnosed multiple myeloma. The deeper and more durable MRD responses observed with this combination suggest a potential for long-term disease control and improved patient outcomes. Further research is ongoing to explore the optimal duration of treatment and to identify biomarkers that can predict which patients are most likely to benefit from this approach.
The approval of teclistamab plus daratumumab for relapsed/refractory multiple myeloma after at least 1 prior line of therapy also demonstrates the continued evolution of treatment options for this disease according to Onclive.
This research represents a significant step forward in the management of multiple myeloma, offering hope for improved outcomes for patients who may not be suitable for more intensive treatment approaches.
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Disclaimer: This information is for general knowledge and informational purposes only, and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.
