COMy 2023 | The role of proteasome inhibitors in the treatment of R/R multiple myeloma

Proteasome inhibitors have been introduced about 20 years ago in the management of relapsed/refractory multiple myeloma. So the first studies have been done with bortezomib. Later on, there was the introduction of carfilzomib and then the third proteasome inhibitor ixazomib. Now today we are 20 years later compared to the first study results, and we can say that proteasome inhibitors are still a very important backbone in the management of multiple myeloma. There are several reasons for that. From a preclinical point of view, it was already shown in the early days that proteasome inhibitors can be combined with immunomodulatory drugs, with steroids and even with chemotherapy, and this is result in many active treatment regimens. A couple of years ago when the anti-CD38 monoclonal antibodies were introduced, they were also hooked up to these PI-based regimens. Currently proteasome inhibitors are still widely used in frontline treatment for transplant-eligible patients like in the VRd or dara-VRd regimen. There are interesting data with KRd as the induction backbone. For non-transplant eligible patients who are not candidates for DRd, there is the attractive combination of dara-VMP or even VRD. According to the EHA/ESMO guidelines for the management of patients with relapsed myeloma as published in 2021, we see that proteasome inhibitors like bortezomib, carfilzomib and to a lesser extent ixazomib are present in the far majority of all the different treatment regimens.