The past, the present and the future of immune checkpoints inhibitors in multiple myeloma

Myeloma genesis is a very complex mechanism in which the interaction between plasma cells and microenvironments with immune cells, cytokines and chemokines have a central role. In the last years, the improved knowledge of immune checkpoint models led to the development of new drugs (anti-PD1/PD-L1 axis or anti-TIGIT) that now have a crucial role in the treatment of many hematological malignancies.

In this review, the current significant literature was discussed. In the past, initial trials combining immune checkpoint inhibitors (ICIs) with immunomodulatory drugs or proteasome inhibitors demonstrated suboptimal results in terms of efficacy and safety. On the other hand, recent trials based on the combination of ICIs with immunotherapies, such as CAR-T cells or bispecific antibodies, are a particularly promising area of investigation.

Our idea after the evaluation of scientific literature is that despite the past, ICIs may represent a promising therapeutic approach for myeloma, particularly when combined with CAR-T cells or bispecific antibodies. By targeting immune evasion mechanisms, ICIs may enhance the efficacy of these treatments and provide new hope for patients with resistant disease. Future research will be crucial to further elucidate their optimal use in myeloma and to develop personalized treatment strategies.