EHA 2023 | KarMMa-3: PROs in patients with TCE R/R myeloma treated with ide-cel vs standard regimens

So at this meeting in Frankfurt, we present the data on patient-reported outcomes from the KarMMa-3 three trial. So very briefly, KarMMa-3 is a prospective randomized Phase III study where patients with relapsed myeloma were randomized between either standard of care regimens – five different regimens that could be selected – compared to one single infusion of a BCMA-targeting CAR-T cell called ide-cel. And this study was conducted in patients who had received two to four prior lines of therapy and who were exposed and mostly refractory to the standard classes of agents: proteasome inhibitor, IMiDs, and an anti-CD38 monoclonal antibody. So, a heavily pretreated population, and, as we know, those patients usually have a poor quality of life because of the disease burden but also because of the impact of previous treatment.

So, that study proved the superiority of ide-cel over the standard of care regimens in terms of progression-free survival, overall response rate, CR rate and MRD negativity. But then, of course, one could question: well, what is the impact on the quality of life of those treatments? And so this was in particular measured in this study. So how did we do this? Well, we used the standard QoL scores, which is the EORTC QLQ-C30 score and then the myeloma sub-score, which measures the impact of the disease and the treatment, and also EQ5D. And so it was measured by patient-reported outcomes just at the time of inclusion in the study and then after the infusion of ide-cel, and so when the drug-based treatment was given, every month for a total duration of two years.

So what were the results? Well, the global conclusion is that the quality of life in the ide-cel arm is much better compared to the quality of life in the drug-based treatment. And this is not only from a statistical point of view, but also it is clinically meaningful. And particularly looking at some sub-scores like fatigue, pain, physical functioning, cognitive functioning, disease-related symptoms, they were all better in the ide-cel arm, and the improvement was rapid and it was sustained. So in that regard, it is, I think, a major conclusion that CAR-T based treatment like ide-cel in the KarMMa-3 study does not only result in longer PFS and deeper responses but is also translated in a significantly better quality of life.

And to conclude, I think those of us who have experience with CAR-T treatment, we all agree that it’s such a benefit for patients to have a long treatment-free interval, and this is exactly reflected by this better quality of life –  good responses, good disease control, but also off treatment for a long period of time.