Abstract
Despite the introduction of several therapies in recent years, multiple myeloma (MM) remains a hematologic malignancy difficult to treat due to its extreme inter- and intra-patient heterogeneity. However, at the 2024 major international conferences, very significant data have emerged on new approaches that can improve outcomes even in high-risk or very advanced diseases. Up-front quadruplet combinations, including anti-CD38 monoclonal antibodies, proved to be the best therapy in terms of depth of response and long-term efficacy in both transplant-eligible and not-eligible patients with MRD assessment that could play a key role in determining the duration of therapy, avoiding unnecessary overtreatment. However, quadruplets also fail to overcome the negative prognostic value of high-risk cytogenetics or circulating tumour cells; therefore, in patients with these features, alternative approaches will have to be evaluated. Moreover, considering that not all patients, particularly older and frail ones, will be able to undergo such therapies, it will be necessary to refine the ability to identify the most appropriate therapy for each patient. Bispecific antibodies and CAR-T cells represent the new frontier in the treatment of advanced MM. However, they have shown even more efficacy with less toxicity in early relapses and functional high-risk patients. In the upfront setting, the results obtained with the inclusion of novel immunotherapies are extremely promising. In relapsed/refractory MM patients, agents such as belantamab mafodotin and CELMoDs, in combination with proteasome inhibitors or immunomodulatory agents, may represent another valid option.