ATLAS Trial Confirms Superior Myeloma Survival With KRd Maintenance

Andrzej Jakubowiak, MD, PhD, director of the multiple myeloma program at the University of Chicago, discusses the definitive results of the phase 3 ATLAS trial (NCT02659293), recently published in The Lancet Haematology, which compared carfilzomib (Kyprolis), lenalidomide (Revlimid), and dexamethasone (KRd) to lenalidomide alone as post-transplant maintenance therapy for multiple myeloma. The final analysis confirmed that the KRd regimen is highly statistically superior to the standard of care in extending progression-free survival (PFS). However, the most striking finding of the study was the observation of a superior overall survival (OS) benefit for the KRd arm.

Jakubowiak emphasizes that while clinical trials often focus on PFS, the demonstration of an OS benefit is a critical milestone that should influence clinical decision-making. He argues that while a longer remission is desirable, proving that a treatment actually extends a patient's life provides a much stronger mandate for its use. This survival advantage suggests that the depth of response achieved with the KRd triplet post-transplant translates into long-term clinical gains that cannot always be replicated by rescuing patients with subsequent therapies after they relapse on lenalidomide alone.

The study also addressed the long-standing debate over which patient subgroups benefit most from intensified maintenance. Intuitively, many clinicians expected that high-risk patients would benefit from the extended KRd protocol, and the trial data supported this, showing a significant advantage for those with high-risk cytogenetic features. However, a key takeaway from the ATLAS trial is that this benefit was not exclusive to the high-risk population. The data revealed that lower-risk patients without traditionally aggressive markers also experienced a highly significant improvement in outcomes when treated with KRd, even if they received treatment deescalation.

Based on these findings, Jakubowiak suggests that KRd maintenance should not be restricted solely to high-risk individuals. The broad efficacy observed across different risk profiles indicates that many patients, regardless of their initial risk stratification, stand to gain from the intensified triplet approach. By showing both longer remissions and longer survival, the ATLAS trial provides a compelling argument for reconsidering the current standard of single-agent maintenance in the post-transplant setting.