An Overview of the Most Recent Studies in Multiple Myeloma | Claudio Cerchione, MD, PhD

Hello, I am Claudio Certione. I work in Istituto Romagnolo per lo Stoio della Cura dei Tumori di Namador in Meldola, northern part of Italy, and it's a pleasure today to focus about the novelties in multiple meloma from ASH 2025 in Orlando. In multiple meloma, the diagnostic and therapeutic revolution is continuing, like in last year and here in ASH 2025 in Orlando we have seen outstanding results in all the settings of disease. Starting from frontline treatment, in which we have seen recently outstanding data from Perseus, C.M.N.17 with the potential progression of resurrected until 17 years, and NIMRODS in transplant ineligible patients, in which we have seen incredible data in terms of deepness of response and Mardin negativity. However, some new potential studies are exploring new molecules also in frontline settings, and particularly LINC-RMM4 has explored the Lymphoseltamal as monotherapy in both transplant eligible and ineligible, and I think that data are particularly encouraging for this new generation B-specific antibody, anti-BCMA-CD3. Moreover, also there is a reawakening of Carfilzomib in frontline settings and the COBRA study has compared KRD versus VRD, showing that proteosome inhibitors could have their sense also in the novel layer of multiple meloma in particular settings of patients. What about relapsed refractory settings? I think the most important data is Majestic-3, in which we have seen a comparison between Teclistamab plus Daratumab. Teclistamab we know perfectly, it's a B-specific antibody, anti-BCMA-CD3, together with Daratumab monoclonal anti-CD38 antibody with a regimen that spares dexamethasone with a great increasing in terms of tolerability, quality of life of our patient, it is compared to the standard of care, so Dara PD or Dara PD. Data are incredible in terms of progressive physical survival, in terms of MRD negativity, and also in terms of long-term survival, because this is an important point, there is almost a plateau for the experimental arm, and even if in the first part we can see some toxicity, let's consider that this study started in 2021 when we had no recommendations about the management with new cellular therapies and B-specific antibodies, together we know how to perform a best supportive care with intravenous immunoglobulin, in general we can supplement what the patient needs, we can adequately treat them with prophylaxis, antibiotic, antivirals and so on, so data could be in some way re-elaborated in the new era of supportive care for cellular therapies. We have seen a confirmation of CAR-T2-4 trial, we have seen also a confirmation of an Itocell data with an overall response rate of 97%, and another really important molecule, a new generation B-specific antibodies, anti-BCMA-CD3, is a Tentamig, in combination with pomalidomide has shown exciting data in terms of deepness of response but also in terms of tolerability, I was one of the investigators as co-author of the abstract that has been presented here and I can confirm that synergism between Tentamig and pomalidomide is exciting and also the tolerability is wonderful, so I think that we will see more combination with Tentamig and also further phases of development for this drug. Interestingly we have seen also that for patients that don't respond or lose the response to the conventional used drug we can see new mechanisms of action that are in some way being developed. KTX1001 is an SD2 inhibitor particularly active in patients with translocation 414 but not only, in fact in the study we can see a great population independently from the cytogenetic characteristic, outstanding data in terms of response if we consider that this is an able-reported population and I think that data are encouraging for further developing this drug. KLN1010 is a really interesting CAR-T, this is a force in human study and I have to say that not only the effectiveness is fantastic but also the tolerability thanks to the lack of need of lympho-depletion of our patients, so this can optimize the positioning and in some way also the feasibility of CAR-T and I think that this is another fantastic data we are going to optimize the treatment that we have discovered in last years. Another important data that we have seen are the ones that are arriving from the registries, we know that we have seen many reimbursements of drugs and combinations but we have some unmet medical need to cover and in particular Loneur and Preamble registries have shown some particular sub-analysis in which we can see which is the best sequencing of the agents, which is the best moment to withdraw the treatment because this is another important point, we want to stop the treatment for the patients that have reached the best in some way response because the patients want to live without the treatment, the continuous treatment is not anymore our need and I think that MRD negativity will be the key, the driver point and we have to understand which is the correct time of sustained MRD negativity to optimize in some way the life of our patients. Another important data that we are understanding better how to administrate the drug and I think that this also correlates with the quality of life in interesting sub-analysis from Miraclea study has shown that with the own body delivery system the Isatoxinab new generation anti-CD38 antibody can be administrated at home. I participated with my institution to this analysis and the idea to have a domestic administration of antibodies is something that improves incredibly the quality of life, the patients reported outcome and also the staff satisfaction because we can optimize the places in our hospitals. So all these novelties to confirm that the run toward the cure is not an utopia, is not so far and this is our dream that we are going to realize and this is the best wish that we give to our patients, to their caregiver and to all myeloma researchers. If our videos have helped you in any way and you're able to please consider making a donation to help us continue this important work. 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