Individualizing Therapy for Triple-Class Refractory Myeloma

Suzanne Lentzsch, MD, PhD: Treatment of relapsed/refractory multiple myeloma, especially in triple-class refractory patients, is a challenge in contrast to initial treatment, which is relatively standardized. In initial treatment, there’s RVd [lenalidomide, bortezomib, dexamethasone] and also KRd [carfilzomib, lenalidomide, dexamethasone] for younger patients who are fit. The treatment in later relapse, especially in patients who are triple-class refractory, depends on the goal of the treatment, the adverse effects of prior treatments, and what we wish for in terms of quality of life. I’ll give some examples that might guide you on treatment, because we do not have any data that would offer guidance, like whether it’s better to use selinexor after Blenrep [belantamab mafodotin], or it’s better to use melflufen before selinexor. There are absolutely no data on the sequencing.

When you have a patient who is triple-class refractory, you should really look at the adverse-effect profile of the drug. For instance, with patients who already have very low blood counts and start with grade 3 thrombocytopenia and neutropenia, I’m not sure I would treat them with melflufen, where the main adverse effect is thrombocytopenia and neutropenia. In contrast, when a patient heavily depends on their eyesight—has to drive, needs to work on the computer—I’m not sure I would go with Blenrep, where 50% have a decreased vision and keratopathy that can last quite long. That might not allow those patients to use a computer or drive. Patients who already have a low body weight or struggle with low appetite might not be the best candidates for selinexor, because selinexor can decrease the appetite and lead to fatigue and a low oral intake. Those are things I would consider while deciding whether to use Blenrep, selinexor, or melflufen.

Peter Voorhees, MD: As far as optimal treatment choices for patients with triple-class refractory disease and the various treatment strategies we’ve discussed, there are no data on optimal sequencing of therapy. I can’t tell you that it makes more sense to start with a selinexor-based regime followed by BCMA-targeted strategy or the other way around. Those data do not exist. It certainly is something we hope to have in the future.

Treatment needs to be based on what the patient brings to the table, particularly with regard to past medical history as well as past toxicities with treatments. For example, if you have a patient who has relapsed/refractory disease, has pretty fragile bone marrow reserves, and is predisposed to severe cytopenias in prior lines of therapy, they may not be the best patient for a melphalan flufenamide–based strategy. However, if you have a patient with triple-class refractory disease who hasn’t seen an alkylating agent since their transplant many years ago, and they’ve got robust counts—good neutrophil and platelet counts at the time of their relapse—they would be a very good candidate for melphalan flufenamide with dexamethasone.

For a frail patient who’s been prone to gastrointestinal adverse effects or significant constitutional effects of therapy in the past, selinexor is something you can use, but you have to use fairly cautiously. You should maybe be migrating toward the lower doses. Give it on a once-weekly basis as opposed to the twice-weekly 80-mg dose that’s FDA approved. That needs to be taken into consideration.

With regard to belantamab mafodotin, it’s important that the patient who has ready access to an eye care specialist who has some familiarity with the product and can help guide the hematologist-oncologist on whether it’s safe to continue dosing at the same interval. A patient who is being considered for belantamab mafodotin also needs a good social support network working in their favor. If you have a patient who lives alone and drives themselves back and forth to the doctor with no one available to help them in any meaningful way, and they develop severe reduction in visual acuity as a result of the drug, that’s going to obviously put them in a very bad spot.

All these things need to be considered when making choices. It’s really about the adverse effects of prior therapy and the agents you’re considering when you are making these choices. It’s a practical consideration with idecabtagene vicleucel, the BCMA-targeted CAR [chimeric antigen receptor] T-cell product that was just FDA approved. The patient has to be able to get to a center that can administer the therapy. Just as important, after the apheresis occurs for the manufacturing of the CAR T cells, the patient has to have a viable bridging therapy to keep their disease at bay while those CAR T cells are being manufactured. All those things need to be considered when you’re making choices.

The adverse effects of therapy and safety profile of a particular regimen are always important for patients with newly diagnosed disease as well as those with highly refractory, triple-class refractory disease. As the duration of response with subsequent lines of therapy shortens, quality of life becomes incredibly important. You have to be careful when you’re using these therapies. You have to have an in-depth discussion with the patient about the safety profile of the therapy and what the potential adverse effects are so they can make a good choice about the quantity of life that they may derive from a particular product and what effect that therapy might have on their quality of life.

Transcript Edited for Clarity