EHA 2025 | The impact of patient frailty on frontline therapy in transplant-ineligible multiple myeloma

Patient frailty is always important for any patient at any stage of disease, particularly frontline. We do believe that’s perhaps the most important time point where we can influence how we can successfully manage long-term disease control for patients. It’s becoming increasingly important to recognize different frailty groups in newly diagnosed disease for myeloma simply because the median age of diagnosis is about 70. So you’re looking at patients with advanced age with perhaps comorbidities that can contribute towards that frailty. It’s fair to say that a lot of the newer data that’s come out does have robust information on some of the frail subgroups, not all, but in my opinion, some of the new wave of designs in the newly diagnosed space will certainly have to look at frailty as a subset category that’s relevant. We’re talking, of course, about incorporating bispecific antibodies and other powerful agents frontline, which can be associated with significant toxicity and risks, particularly for frail patients. So in order for us to understand how to serve our patients in the most effective way, we’ll have to have a very good understanding of what are the higher risk subgroups and what are the best regimens for those that are at high frailty versus those that are at low frailty. I’ll also point out that among the two trials that have recently impacted our transplant ineligible or transplant-deferred space in myeloma, so IMROZ trial and CERPHEUS trial, they both have demonstrated about 10% treatment-related mortality. So that is not trivial. Those are significant numbers of patients that can experience death unless we are careful in how to select patients for these powerful multi-agent combinational therapies. That said, I still am a proponent to try and find as many patients as we can and give them these combinational therapies such as quads in the newly diagnosed setting because the efficacy data is very difficult to ignore. These patients are achieving extremely long progression-free survival, duration of responses, and it is because of data like this that we have started thinking about potential functional cure for at least subsets of patients, which means people can end up living perhaps the natural durations of their lifetimes while their myeloma is in deep response without evidence of active disease. So this is a major step forward in myeloma.

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