Dr Landgren on the Efficacy of Dara-KRd in Newly Diagnosed Myeloma Regardless of Transplant Eligibility

"The work we presented last year at ODAC shows that MRD negativity 10-5 is a very strong predictor of long PFS and OS. Given how strong the MRD results are here, we certainly anticipate very strong clinical benefit [with Dara-KRd] from this study."

C. Ola Landgren, MD, PhD, a professor of medicine and chief in the Division of Myeloma in the Department of Medicine at the University of Miami, Miller School of Medicine; director of the Sylvester Myeloma Institute; co-leader of Translational and Clinical Oncology Program and Paul J. DiMare Endowed Chair in immunotherapy at the Sylvester Comprehensive Cancer Center, shared efficacy results with the addition of daratumumab (Darzalex) to carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (Dara-KRd) in patients with newly diagnosed multiple myeloma.

Findings from the phase 2 ADVANCE trial (NCT04268498), presented at the 2025 ASCO Annual Meeting, demonstrated that Dara-KRd significantly improved rates of minimal residual disease (MRD) negativity compared with KRd alone in this patient population, regardless of transplant eligibility.

In the intention-to-treat population, MRD negativity at the 10⁻⁵ threshold assessed by next-generation sequencing (NGS) was achieved in 59% of patients treated with Dara-KRd vs 33% of those treated with KRd (odds ratio, 2.9; 95% CI, 1.8–4.9; P < .0001), Landgren shared.

The benefit of Dara-KRd was consistent across subgroups stratified by risk group and age, he continued. Among patients younger than 60 years, MRD negativity rates were 66% vs 49% (P = .00571); in those aged 60 years or older, rates were 68% vs 42% (P = .00571), favoring Dara-KRd. Subgroup analysis by cytogenetic risk showed a trend toward improved MRD negativity with Dara-KRd in patients with high-risk disease (59% vs 41%; P = .170) and a statistically significant benefit in those with standard-risk disease (71% vs 43%; P = .00375), Landgren added. These findings underscore the potential of Dara-KRd to deepen response, particularly among patients with standard-risk profiles, while also suggesting benefit in select high-risk subgroups, he explained.

At a median follow-up of 31.2 months, progression-free survival (PFS) was 92% with Dara-KRd and 83% with KRd (P = .1400). Although the difference in PFS was not statistically significant at this time point, event-free survival (EFS) favored Dara-KRd (P = .0157). Ongoing follow-up will be necessary to confirm whether these MRD findings translate into long-term improvements in PFS and overall survival (OS), Landgren said.

Previous data presented at the 2024 FDA Oncologic Drugs Advisory Committee meeting highlighted MRD negativity at 10⁻⁵ as a strong surrogate marker for durable PFS and OS, Landgren noted. Given the depth of responses observed in ADVANCE, Landgren asserted that Dara-KRd may offer substantial clinical benefit and represents a compelling regimen for newly diagnosed patients, irrespective of transplant eligibility. Further long-term outcomes from this trial are anticipated to clarify the durability and survival impact of MRD-directed treatment intensification, he concluded.