From Subgroups to Sustained Response: IMROZ Efficacy in Frailty and MRD Outcomes Across Trials
An expert discusses how adding an anti-CD38 antibody to a triplet backbone improved minimal residual disease (MRD) negativity and progression-free survival (PFS) in frail, transplant-ineligible patients with multiple myeloma. He also raises concerns about the real-world feasibility of intensive regimens and emphasizes the need for personalized dosing and further research on using MRD to guide treatment duration and intensity.
A recent subgroup analysis evaluated the impact of adding an anti-CD38 monoclonal antibody to a triplet backbone in patients with transplant-ineligible multiple myeloma. Although this study excluded transplant-deferred individuals, it did aim to assess outcomes in frail patients. Notably, those over 80 years were excluded, so frailty was defined using standard scoring systems. Despite these limitations, the addition of the antibody improved measurable outcomes such as MRD negativity and PFS, with comparable treatment discontinuation rates. This suggests that even frail patients may benefit from more intensive therapy when carefully selected and monitored.
However, concerns were raised regarding the practicality of administering full-dose triplet or quadruplet therapies in a real-world frail population. In both this and other similar studies, patients received twice-weekly proteasome inhibitors for extended durations—an approach not always feasible outside of trial settings. The critique centered on the disconnect between labeling patients as frail or ineligible for transplant while still subjecting them to demanding treatment schedules. It was emphasized that treatment toxicity often relates more to dose and frequency than the number of drugs, highlighting the importance of tailoring regimens based on tolerability rather than defaulting to simplified combinations.
The discussion also touched on the role of MRD negativity as an emerging surrogate end point in clinical trials. Since overall survival and even PFS take years to mature, MRD is increasingly used to provide earlier insights into treatment effectiveness. Although its prognostic value is well established—showing that patients who achieve MRD negativity tend to do better—its role in guiding treatment decisions remains underdeveloped. Future research is needed to determine whether MRD status can safely inform therapy de-escalation or discontinuation strategies, especially given the long durations associated with modern regimens. This would help optimize care while minimizing overtreatment.
