Daratumumab Monotherapy: Achieving MRD Negativity in Multiple Myeloma

Daratumumab monotherapy has emerged as a promising strategy for patients with multiple myeloma who achieve a deep response but remain minimal residual disease (MRD) positive. The recent DART4MM phase 2 trial investigated whether this monoclonal antibody could eradicate residual disease after first-line therapy. Specifically, the study focused on patients in at least a very good partial response (VGPR) who were still MRD-positive.

Improving Outcomes with Daratumumab Monotherapy

In this multicentric trial, researchers evaluated 110 eligible patients with newly diagnosed multiple myeloma. Among these participants, 50 patients who were MRD-positive received daratumumab monotherapy for six months. At the primary endpoint, 30% of these patients successfully converted to MRD-negative status. Furthermore, 22% of the cohort maintained this negativity at the 24-month mark. This highlights the potential of consolidation therapy to deepen clinical responses in the front-line setting.

Moreover, the survival data underscore the clinical significance of achieving MRD negativity. Patients who became MRD-negative at least once experienced a median progression-free survival (PFS) of 61 months. Consequently, this outperformed those who remained MRD-positive, who had a median PFS of only 26 months. Additionally, this survival difference was statistically significant with a p-value of 0.0009. Therefore, the study results suggest that MRD conversion serves as a strong predictor of long-term patient outcomes.

Conclusion and Clinical Implications

Importantly, the trial findings indicate that daratumumab monotherapy is effective even in patients previously naïve to the drug. Notably, while 58% of patients eventually relapsed at a median follow-up of 50 months, many remained progression-free for nearly four years. In conclusion, these insights provide a compelling rationale for using MRD status to guide consolidation treatment decisions in newly diagnosed multiple myeloma.

Frequently Asked Questions

What is the role of daratumumab monotherapy in MRD-positive patients?

Daratumumab monotherapy helps eradicate residual cancer cells in patients who have achieved a deep clinical response but still show traces of disease after their initial treatment.

How significant is MRD-negative conversion for survival?

Achieving MRD negativity is highly significant. Specifically, it correlates with significantly longer progression-free survival compared to patients who remain MRD-positive throughout treatment.

What were the long-term results of the DART4MM trial?

The trial showed that patients achieving MRD negativity had a median PFS of 61 months. Additionally, many patients remained progression-free at a median follow-up of 44 months despite early positivity.

Disclaimer: This content is for informational and educational purposes only and does not constitute medical advice. Always seek the advice of a qualified healthcare provider with any questions regarding a medical condition. Refer to the latest local and national guidelines for clinical practice.

References

1. Gozzetti A et al. MRD-negative conversion with daratumumab monotherapy in newly diagnosed multiple myeloma patients in ≥VGPR/MRD-positive after first-line therapy: Final analysis of the open-label, single-arm multicentric phase 2 trial DART4MM. Br J Haematol. 2026 Mar 26. doi: 10.1111/bjh.70448. PMID: 41888038.


2. Kumar L et al. Daratumumab in Indian patients with relapsed and refractory multiple myeloma: a prospective, multicenter, phase IV study. BMC Cancer. 2023 Dec 20;23(1):1260. doi: 10.1186/s12885-023-11663-z.


3. Moreau P et al. Daratumumab, bortezomib, thalidomide, and dexamethasone in newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019 Jul 6;394(10192):29-38.