From bench to bedside: breakthroughs in targeted therapies for multiple myeloma

In this comprehensive review, we explore the way targeted therapies for multiple myeloma have changed over time, with a bench-to-bedside perspective of how laboratory discoveries became clinical approaches. Recent breakthroughs changed patients' outcomes significantly. Our study covers proteasome inhibitors, immunomodulatory drugs, monoclonal and bispecific antibodies, and CAR-T cell therapies, Delving into the efficiency risks and synergetic impacts of targeted treatment. Background: Multiple myeloma is a complex hematological malignancy of bone marrow plasma cells. While conventional therapies have progressed, relapse is still a major problem, and it shows the necessity of more inventive treatments. In this scenario, immunotherapy and targeted therapies represent a promising beacon of hope. Even though the challenges on the way, like long-term remission and drug resistance, still need to be solved by constant research and developing new treatment strategies. Results: Our review combines recent significant data from pivotal clinical trials and observational studies in targeted therapies of multiple myeloma (MM). Proteasome inhibitors such as bortezomib which molecularly targets dihydrolipoamide dehydrogenase (DLD) are still one of the drugs with the most efficiency in targeting refractory multiple myeloma. It has been shown that DLD inhibitors such as CPI۶۱۳ have a synergistic anti-MM impact with bortezomib. Immunomodulatory drugs (IMiDs) especially lenalidomide and pomalidomide are some of the backbones of therapy. Besides that, iberdomide and mezigdomide have shown promising activity in treating IMiD-resistant patients. But they are in the process of phase ۳ finding. Antibody_drug conjugated (ADCs) have been a revolutionary finding in the field of targeted therapies. When monoclonal antibodies, which specifically target proteins on tumor cells, can now be combined with potent cytotoxic agents, and enhance therapeutic efficacy. Bispecific antibodies targeting BCMA, GPRC۵D, and FcRH۵ are highly effective even for patients with a history of being heavily treated. Now their use is being considered in earlier stages of therapy. Combining BsAg with other drugs can help overcome resistance mechanisms and improve treatment effectiveness. Up-to-date achievement in CAR-T cell therapy approved CAR T cell products -idecabtagene vicleucel and ciltacabtagene autoleucel to be used in the United States and Europe for patients who already passed three lines of therapy. Updates outcomes from CARTITUDE-۴ would probably lead to approval of a new drug for earlier lines of therapy. Unfinished trials like CARTITUDE-۵ and CARTITUDE-۶/EMN-۲۸ will define if CAR-T cell belongs in front-line treatment or not. Conclusion: In this comprehensive review, we analyzed the game-changing effects of targeted therapy on multiple myeloma. Proteasome inhibitors, immunomodulatory drugs, monoclonal and bispecific antibodies, and CAR-T cell therapies continue to hold a critical position in the treatment of MM. In-progress experiments, for instance, CARTITUD-۴ and other developments highlight how fast treatments are going through a transformation. This can lead to an inspiring hope for prolonging life expectancy and quality of life for patients.

کلیدواژه ها:

Multiple Myeloma (MM) ، Targeted Therapies ، Proteasome Inhibitors (PIs) ، CAR T-cell Therapy ، Bispecific Antibodies (BsAg)