KRd Appears to Exhibit Greater Outcomes in Standard-Risk Multiple Myeloma

Adding an additional agent to a regimen consisting of carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) for multiple myeloma or putting a greater emphasis on minimal residual disease (MRD) negativity at 10-6 are among the next steps for research in evaluating KRd in patients with high-risk disease, according to Andrzej Jakubowiak, MD, PhD, a professor of Medicine and director of the Myeloma Program at the University of Chicago.

CancerNetwork® spoke with Jakubowiak at the 22ndAnnual International Myeloma Society (IMS) Meeting and Exposition about his presentation of a high-risk subset of patients from the phase 3 ATLAS trial (NCT02659293) evaluating KRd following autologous stem cell transplantation in those with newly diagnosed multiple myeloma. He described the potential discrepancies in benefit observed in those with high-risk vs standard-risk disease.

He began by emphasizing that benefit was seen among both patient groups but suggested that a greater benefit was observed among those with standard-risk disease, particularly for progression-free survival (PFS). Highlighting Kaplan-Meier curves that may show a closing of the gaps, Jakubowiak suggested that benefit for patients with high-risk disease may be extrapolated with an analysis of MRD negativity at the 10-6level vs the 10-5 level. He concluded in outlining considerations for future research for this high-risk subset of patients, which include evaluating MRD negativity at the 10-6 level and adding an additional agent to help bolster outcomes.

Transcript:

First, I will stress that benefit was seen for both high-risk and standard-risk patients, but the benefit appears bigger for patients without high-risk [disease]. If you compare patients receiving KRd, with or without high risk, there is slightly better PFS for standard-risk, non–high-risk patients. Bringing [us] closer to standard risk, there are a couple of Meier curves in high-risk patients, but [they do] not completely eliminate the gap. We think that the reason [for] that was we potentially could see that benefit if we would be able to analyze it based on MRD at 10-6.

[A similar] proportion of patients did achieve MRD negativity at 10-6, but we did not have studies set up that we had consistently analyzed MRD at this level. All patients were analyzed at 10-5, and this was the study measure of de-escalation. Maybe that is contributing to the fact that KRd improves––quite significantly––outcomes in high-risk patients, but it does not, at this moment, at least completely, eliminate the high-risk impact. That’s something that we need to work on, possibly by adding an additional agent to KRd and maybe focusing on patients who achieve MRD negativity at 10-6.

Reference

Jakubowiak A, Wrobel T, Jamroziak K, et al. Carfilzomib, lenalidomide, and dexamethasone (KRd) after autologous stem-cell transplantation in patients with newly diagnosed multiple myeloma: analysis of high-risk subset in phase 3 ATLAS trial. Presented at: 22nd Annual International Myeloma Society (IMS) Meeting and Exposition; September 17-20, 2025, Toronto, Canada. Abstract OA-51.