Dr Adriana Rossi reviews the therapeutic options for patients with triple-class refractory multiple myeloma in terms of mechanism of action and safety profile.
Adriana Rossi, MD: Patients like this who’ve progressed on 4 prior lines of therapy have very limited options. Certainly consideration for a clinical trial would be advised. If they have access to either an academic center or otherwise are able to participate in clinical trials, that is always a good option. But especially given her age, and we don’t know about her comorbidities, I think the option of belantamab was a very good one, not only because this is exactly the population that we’ve studied, but it is a very tolerable and very effective therapy for this patient population.
Belantamab mafodotin is an antibody-drug conjugate that targets BCMA. It carries a toxic payload known as MAF, which is known to cause ocular toxicity. I think it’s the first antibody-drug conjugate, or ADC, that we have available in myeloma. It’s also the first BCMA-targeted therapy. Both of these make it a very exciting option. It does come with the unique ocular toxicity, which has gotten quite a bit of attention. But interestingly, I have a number of patients who have tolerated it. About half of patients will go on to develop ocular toxicity, but the vast majority will improve with dose delays or dose reductions. Just as in the clinical trials, my experience has also been that maybe the dosing was a little optimistic. And if we dose it less frequently or at a reduced dose, we can get patients to stay on therapy for much longer. The schedule, which is once every 3 weeks, is something patients really appreciate.
The current treatment the patient is on, selinexor, is another recent addition to our armamentarium. In this case, it is an XPO inhibitor, which is a nuclear transport. So, it’s a protein that the cells use to get rid of tumor suppressors and growth factors. And by inhibiting them, these accumulate in the nucleus and lead to cell death. The drug is oral, which I think is one of the big selling points, especially in this past year, with reducing visits to the office. It was a good time to have it added to our menu of options, but it does come with significant toxicity itself, namely central nausea. So, patients usually require a number of antiemetics. There again, I think approval on the studies started with maybe an optimistic dosing of twice a week. As we’ve moved through different studies and different combinations, I think we’ve learned that once-a-week dosing makes it much more tolerable, and dose reducing as necessary. Again, not all patients will be able to tolerate the full dose as approved.
Transcript edited for clarity.
Case: A 75-Year-Old Woman with Triple-Class Refractory Multiple Myeloma
Initial Presentation
Clinical Workup
Treatment
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