BSH 2023 | Approaching penta-refractory multiple myeloma: challenges and promising agents

Penta-refractory myeloma clearly refers to refractoriness to the CD38+ monoclonal antibody, two immunomodulatory drugs and two proteasome inhibitors of different types, the boronic acid and the epoxy ketone. The proportion of patients who have penta-refractory disease is gradually rising because more and more patients are getting more lines of therapy. So, this is a here and now problem for us. The challenge here is retrospective data shows that the overall survival of these patients can be significantly less than six months. Therefore, meaningful drug classes have to be brought in to improve response rates in these patients. Very few drugs particularly have focused on the penta-refractory setting. But I do have to point out selinexor as being one drug that has specifically got its approval in that kind of penta-refractory state, and this certainly can be considered. We now have the approval of Selinexor-velcade-dex in the UK for patients, it’s MHRA approved, it’s not NICE reimbursed, but it’s MHRA approved. But that’s for more earlier relapsed patients based on the BOSTON study. The point I’m making, selinexor does have some effect in the penta-refractory state and it’s a very different drug class. If we look at all the BCMA-targeted studies, there is clearly reports which look at those penta-refractory patient population within these BCMA-targeted studies, be it cilta-cel, ide-cel, belantamab and teclistamab which are all approved now and available. Clearly, we don’t have the ability to give ide-cel or cilta-cel in the UK, but belantamab is available for us to use through a particular scheme and can be available for patients and meaningful responses have been obtained in penta-refractory patients.