Frailty Adaptive Therapy in Newly Diagnosed Myeloma Patients | Maria Victoria Mateos, MD | EHA 2024

When we have in front of us newly diagnosed myeloma patients, especially here in Europe, we do usually distinguish between transplant eligible and transplant ineligible population. But now we are observing how new combinations are coming for newly diagnosed myeloma patients basically based on quadruplet combinations including proteasome inhibitor, immunomodulatory drug, dexamethasone and anti-CD30H monoclonal antibodies. And the key question is who is eligible for the quadruplet combination? And I think that this is in line with an approach in which we are moving forward, frailty adapted therapy in the newly diagnosed myeloma population. And the key question is how to define who patient is fit and who patient is frail, maybe not eligible for the quadruplet combination. The International Myeloma Working Group published many years ago in 2005 an International Myeloma Working Group frailty score basically based on the chronological age and the capacity the patients had to do their daily living activities. This IMWG frailty score is valid but it is true that as soon as a scale incorporates the chronological age as factor for defining the frailty, whatever patient older than 80 is frail by definition. In addition, this questionnaire resulted in a very long list of questions patients had to reply. And there was another approach, modified IMWG frailty score including the chronological age, the performance status and the charge on comorbidity in this. And this modified IMWG frailty score is also valid and it has been utilized in many clinical trials to distinguish fit from frail patients in order to see how in general frail populations do usually go with a lower response rate and with a poor outcome in comparison with the fit. The Spanish Myeloma Group is working in another different geriatric scale and it is, I would say, more complete because our geriatric assessment in the IMWG score does include a list of different items evaluating the polypharmacy, the gait speed, the nutritional status, the mood, the psychological status, the comorbidity index. So at the end this scale allowed us to distinguish fit versus frail patients. I think that we have to move in this direction because when we have patients with newly diagnosed multiple myeloma, we have to try to offer them the most effective therapy but at the same time the safest one. And we have to try to avoid or even to reduce to 0% the early mortality in relation with adverse events. And this is the reason why I consider that in the future I would say that maybe fit patients with newly diagnosed myeloma patients are going to be eligible for the quadruplet combination. After induction with this four-drug-based combination, some patients can go to transplant, maybe some patients can go to CAR-T or even they can continue with the anti-CD30H monoclonal antibody, lenalidomide and dexamethasone. But we have to try to identify very well the more frail subgroup of patients in which maybe with that index is enough we will be able to deliver median PFS of approximately five years. Overall survival 90 months reported during this EHA congress and this is what I would like to summarize. Frailty adaptive therapy I think that is something necessary even in our clinical activity because again I repeat we have to try to offer to our patients the most effective combination but at the same time the safest one.