A 72-Year-Old Man With Heavily Pretreated, Relapsed/Refractory Multiple Myeloma - Episode 2
Sagar Lonial, MD, FACP, reviews and comments on the treatment options for patients with triple-class relapsed/refractory multiple myeloma (RRMM).
Sagar Lonial, MD, FACP: When we think about treatment options for a patient who has had 4 or more prior lines of therapy, the approved options are limited and speak to the fact that the PFS [progression-free survival] and overall survival rates are quite short for these patients. What often happens is the use of cytotoxic chemotherapy regimens, such as DCEP [dexamethasone, cyclophosphamide, etoposide, cisplatin] or VDT-PACE [bortezomib, dexamethasone, thalidomide, cisplatin, doxorubicin, cyclophosphamide, etoposide] and hyper-CVAD [cyclophosphamide, vincristine sulfate, doxorubicin hydrochloride, dexamethasone], that use combinations of alkylating agents and steroids that historically represented early line therapy—given the advance of novel agents in the [treatment] of patients—have moved forward into this situation. Alternatively, one can recycle other novel agents that have been used, particularly retreatment with an anti-CD38, an IMiD [immunomodulatory imide drug], and/or a proteasome inhibitor. Unfortunately, what we know about that is although one may get an initial response, the duration of response ends up being quite short. In this situation, the patient was offered treatment with belantamab mafodotin [belamaf], which is a BCMA [B-cell maturation antigen]-directed antibody drug conjugate that has a very novel and unique mechanism of action.
Functionally, the immunotoxin is different than one that we’ve seen in any other antibody drug conjugate molecules in all of oncology. The immunotoxin is something called MMAF, which is different from MMAE, which is more commonly used in this clinical situation. This allows the direct targeting of chemotherapy agent toward 2 cells that express BCMA. Because BCMA is a little less ubiquitously expressed than other antibody targets in myeloma, such as CD38 or SLAMF7, what this means is that you’re effectively delivering local chemotherapy to the tumor cell itself because BCMA is not expressed on many cells beyond plasma cells. This immunotoxin is somewhat unique and represents the first antibody drug conjugate approved in myeloma and the first BCMA-directed drug in the context of myeloma, as well.
BCMA is a target that has not been used, and this patient has not been exposed to that target to date. This offers a significant benefit, particularly in patients who may have significant comorbidities or difficulty traveling back and forth between the clinic and their home, because belamaf has to be given only once every 3 weeks; this means visits to the office are relatively few. On the other hand, the other approved agent in this context is selinexor, which is an XPO1 inhibitor, an FDA-approved combination with dexamethasone in the context of refractory myeloma—particularly penta-refractory or myeloma. In this context, selinexor given on a twice-weekly dosing schedule is a treatment that could potentially be given at home; however, the twice-weekly dosing schedule that was approved by the FDA in the basis of the STORM trial [NCT02336815] made office visits frequent and required for supportive care—particularly nausea, vomiting, diarrhea, and anorexia. With once-weekly dosing of selinexor—either with dexamethasone or in partnership with bortezomib or carfilzomib, or even combining with pomalidomide—the incidence of the GI [gastrointestinal] toxicity has dropped markedly but remains an issue in supportive care. Hydration, energy, fatigue, and asthenia are all adverse effects that persist and require interventions with additional supportive care measures. It’s clear that both belantamab mafodotin and selinexor have significant activity in the population of patients with refractory myeloma. If patients can tolerate therapy, they may gain significant clinical benefit, but the idea of trying to anticipate and manage the potential adverse events is quite different between these 2 approved agents in the context of refractory myeloma.
Transcript edited for clarity.
A 72-Year-Old Man with Heavily Pretreated, R/R Multiple Myeloma