SOHO 2021 | Early relapse: options for rescue

When we have in front of us relapsed or refractory myeloma patients, basically after the first or the second line of therapy, we have to incorporate basically the treatment history as one of the main drivers in order to select the appropriate rescue therapy.

Together with the treatment history, we have to consider the frailty, the disability, the risk status, and the lifestyle of the patients. And as the treatment for myeloma is rapidly evolving, at the moment of the first relapse, most patient right now have been previously treated with proteasome inhibitors and IMiDs, and basically most patients have refractory to lenalidomide.

So, the first question is if we are going to treat these patients at first relapse with anti-CD38 monoclonal antibodies based combinations, and this would be the case for carfilzomib and dexamethasone plus either daratumumab or isatuximab, or pomalidomide and dexamethasone plus daratumumab.

And if we prefer to utilize the combinations three for anti-CD38 monoclonal antibodies, one of the possibilities would be pomalidomide in combination with bortezomib and dexamethasone. In the future, we can potentially utilize selinexor in combination with bortezomib and dexamethasone. And maybe we are going to reserve venetoclaxta for patients with 11;14 translocation.

And after these possibilities for early relapses, then for subsequent relapses, if the patient is naive for pomalidomide, a possibility is to utilize PomDex plus elotuzumab, or PomDex plus cyclophosphamide or PomDex plus isatuximab. Other possibilities would be drugs with a novel mechanism of action, like selinexor or melflufen. And we are going to reserve definitely the BCMA-targeted therapy. Today it’s restricted for the triple-class exposed and maybe refractory population, but in the future, the sequencing of the therapy will move this novel strategies earlier on.