COMy 2026 | Frontline and R/R myeloma: an overview of the current treatment landscape

The treatment of multiple myeloma is continuing to revolution in the last years, and particularly in the front-line setting has seen many novelties, starting from the introduction of isatuximab, a new generation of anti-C38 monoclonal antibody that has become a new potential backbone, starting from elderly transplant ineligible patients in which isatuximab added to VRd, bortezomib and dexamethasone, is giving incredible results in terms of deepness of response, in terms of quality response, quality of life, and I think that IMROZ combination, according to the exciting data about MRD negativity and sustained MRD negativity, can become the standard of care in this category of patients. In transplant eligible, we have daratumumab VRd that, according to PERSEUS EMN17 clinical trial, has become the new standard of care and now reimbursed also in my country, in Italy, and are incredible and I think that the idea of a projection of a PFS till 17 years in the median I think that can take the patient to think to myeloma in a really different way let’s not forget that we have also GMMG HD7 with this actuximab, BRd, that is not reimbursed in this moment, but can be another potential standard of care, also according to MRD negativity data and in the idea of deepness of response for transplant eligible patients. Some patients that are not able to come often in the hospital, dara, lenalidomide, dexamethasone continues to be a potential standard of care. And let’s not forget that many clinical trials are going in this setting. We have to see the positioning of bispecific antibodies, CAR-T, according to the trials that are ongoing. And also belantamab mafodotin, according to DREAMM-9 and the ongoing DREAMM-10, can find the place in the frontline treatment. So I think that we will have new revolutions in the upcoming years. In terms of relapsed/refractory multiple myeloma, we know that in this moment, starting from early phase relapses, we have incredible amount of exciting combinations. Starting from teclistamab and daratumumab, as we have seen at last ASH, this is an incredible combination with exciting data, and I think probably together with the CAR-T, cilta-cel that have been now reimbursed, also in my country, according to CARTITUDE-4, these are the standards of care in patients that are in some way young, fit and have the condition to reach a very good and sustained in the time result. Let’s not forget that we have other combinations for people that are naive for anti-CD38 monoclonal antibody. Isatuximab, carfilzomib, dexamethasone remains the standard of care and is also a wonderful bridge for patients that are waiting for CAR-T, for cilta-cel. Let’s consider that we have also have belantamab mafodotin with the incredible data coming from DREAMM-7 and DREAMM-8 in combination respectively with bortezomib, with pomalidomide. This is an this is an antibody drug conjugate, the results are incredible and tolerability in earlier lines with the lower dose is absolutely more than acceptable so I think this is another potential standard of care also in patients that are coming from a front line daratumumab base but also in patients that are that are dara naive if they’re for example, lenalidomide maintenance. Maintenance is also something in which we have to consider that in this moment we have only lenalidomide, but according to PERSEUS, we will have dara-lenalidomide and there are ongoing results of the trials with bispecific, for example, elranatamab and teclistamab maintenance. So also in this case, we will go to potentiate the maintenance approach. In later relapse, we have many data with new drugs, new combinations. And I think that we have to consider that the cilta-cel in fourth line, according to CARTITUDE-1, 33% at 5 years of PFS can be something that can really change the lives of our patients. Let’s consider that we have also monotherapy with elranatamab or teclistamab that are also really effective, well-tolerated. Data of deep response are also quite exciting. And we have to decide who is the right patient for every drug in my idea we have to think better in terms of sequencing and we have to consider that probably also an anti-BCMA-based sequencing can be something that could be effective we have some data from international institutions that collected the real world. Antibody-drug conjugate, belantamab mafodotin, bispecific antibodies, elra, teclisamab, and then linvoseltamab, etentamig. And in some way, CAR-T, cilta-cel, and ide-cel are not the same drug. So the idea of sequencing them to offer the best to our patient is something that we have to better investigate. In other relapsed patients, let’s not forget selinexor, XPO1 inhibitor that we can use in combination with bortezomib and dexamethasone with quite good tolerability for prophylaxis for gastroenteric tract is done very well, and we do netupitant and palonosetron as prophylaxis, and we are really well our patients and let’s not forget melflufen a new way of intending chemotherapy really selected really personalized with the very good tolerability and the fantastic schedule because with one infusion every four weeks patient can have a new treatment, another mechanism of action and in some way this can be considered also as a bridge for cellular therapies or also in some way as a therapy in which we want to change mechanism of action for example between anti-BCMA bispecific antibodies and talquetamab and something like that. In real world, we are also collecting data and in some way analyzing them. Melflufen is something that is giving in our daily practice data that are also improving the ones of registrative trials, so let’s not forget this drug. And I think that other combinations are arriving. We are going with a lot of phase one clinical trials. We have to discover how is the life after CAR-T or in terms of refractoriness to CAR-T. So I think the best has to come. And I think that the novelties will be available as soon as possible. And the cure of multiple myeloma is not far anymore. And this is the best wish that we give to our patients, to their caregiver and to all myeloma researchers.

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