VIDEO: Monoclonal antibodies, CAR-T and more for multiple myeloma treatment

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So multiple myeloma is a disease of clonal plasma cells and we are very fortunate to have several approved therapeutic options, often using combination to obtain very deep responses. Proteasome inhibitors such as bortezomib or carfilzomib, immunomodulatory drugs, as lenalidomide and pomalidomide and steroids have been now used for at least 15, 20 years and remain the backbones of most of the initial combination in regimens that we all use such as VRD, KRD, or RD.

Another class of drugs that has been used very commonly, especially a second line of therapy, includes anti-CD38 monoclonal antibodies such as daratumumab and isatuximab, and more recently, these two medication has been tested also as frontline therapies together with the proteasome inhibitors or immunomodulatory drug either for transplant-eligible patients or transplant-ineligible patients as noted in recent publication or presentation at meetings such as ASCO and ASH in the PERSEUS, MAIA, and IMROZ trial.

Another new alternative approach that's being used in myeloma implies the use of either bispecific or T-cell engagers antibodies and CAR-T therapies, which can activate immune system and promote anti-myeloma immunity. Teclistamab, elranatamab, and talquetamab are bispecific antibodies that targets either BCMA, the first two one, or GPRC5D, while ide-cels and cilta-cels are the two CAR T cellular products against BCMA that have been approved. So all these therapies are relatively new. They've been approved in the past, between like one and three years, and they are mainly using patient with relapsed/refractory myeloma after one to four lines of therapies depending on different approval labels. And then there are some other type of different drugs that are used not as common in the one that I mentioned but they can still be effective in patients.

There is a monoclonal antibody called elotuzumab that targets SLAMF7, usually in combination with pomalidomide and dexamethasone. There is an XPO1 inhibitor called selinexor that is used especially in combination with bortezomib. And then venetoclax, it is a BCL-2 inhibitors, has been shown, such as in the BELLINI trial, being especially effective in patient with a specific chromosomal translocation that is translocation 11;14. And finally, worth to mention that is also like the use of bisphosphonate, specifically pamidronate and zoledronic acid, that are used for the management of bone disease in myeloma and have been shown to reduce skeletal complication, fracture, bone pain, and also improve bone density. So this is kind of like the whole spectrum of medication that we have to treat myeloma, and especially in the relapsed/refractory setting, we can be a little bit creative and combine different of this drug to benefit our patients.