Dr Landgren on the Rationale for Assessing Daratumumab Plus KRd in Newly Diagnosed Myeloma

“The background of this study was based on the fact that modern combination therapies in [patients with] newly diagnosed multiple myeloma continue to deliver deep and durable responses reflected in high rates of MRD negativity, and this is found independent of transplant eligibility for patients in the newly diagnosed setting.”

C. Ola Landgren, MD, PhD, a professor and chief of the Division of Myeloma in the Department of Medicine at the University of Miami, Miller School of Medicine; director of the Sylvester Myeloma Institute; coleader of the Translational and Clinical Oncology Program; and the Paul J. DiMare Endowed Chair in Immunotherapy, discussed the background and rationale for evaluating carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) with or without daratumumab (Darzalex) for the treatment of patients with newly diagnosed multiple myeloma.

The multicenter, randomized phase 2 ADVANCE trial (NCT04268498), the design of which was presented at the 2025 ASCO Annual Meeting, investigated the combination of daratumumab and KRd for the treatment of patients with newly diagnosed multiple myeloma, Landgren began. He noted that in the multiple myeloma landscape, there are modern combination therapies, particularly in the newly diagnosed setting. These advances continue to demonstrate deep and durable responses and have been observed through minimal residual disease (MRD) negativity, which has also been determined regardless of transplant eligibility in patients with newly diagnosed multiple myeloma, he added.

Additionally, MRD negativity is known to be associated with progression-free survival and overall survival, and has recently been established as an early end point for accelerated approval, Langren continued. Specifically, results from the April 2024 FDA Oncologic Drugs Advisory Committee meeting revealed that MRD could be used as an end point for accelerated approval in new treatments for patients with multiple myeloma.

Therefore, the rationale for ADVANCE is to potentially offer another potential standard of care option for the treatment of patients with newly diagnosed multiple myeloma that is open to patients who are transplant eligible, transplant ineligible, and transplant deferred.