Treatment Considerations for Triple-Class Refractory MM


Sagar Lonial, MD, FACP, discusses factors to consider when selecting later lines of therapy for patients with triple-class refractory multiple myeloma (MM).

Sagar Lonial, MD, FACP: One of the emerging challenges that we have in myeloma is the group of patients who are triple-class refractory. Patients who are resistant to proteasome inhibitors, immunomodulatory agents, and CD38 antibodies. Although our initial therapies can be highly effective, that group of patients is a growing patient population because these classes of drugs have been around for so long that most patients have been exposed to them once or twice in their disease journey. Fortunately, in the last couple of years, we have had a couple of new treatment options that have made a big difference in what we do for these patients overall.

The 2 big classes that we think about are agents that target BCMA. The FDA-approved agent that goes after BCMA right now is belantamab mafodotin, and the other class is selinexor or the XPO1 inhibitors that prevent movement of oncogenes across the nuclear membrane. It is those 2, cytotoxic chemotherapy combinations, or the recycling of previous drugs that represent the main focus for patients who are not going to go on clinical trials.

In balancing what approach one is going to take in the context of this triple-refractory patient population, a number of factors that come into play. The coronavirus pandemic has also played a role in some of this decision-making. Belantamab mafodotin is an infusion that is given every 3 weeks, so it does not require frequent visits to the infusion center or to the physician’s office. It requires partnering with an ophthalmologist, but that can often be done on the same day as the clinic visit to the oncologist to try to partner the ophthalmologic exam with the oncologic exam and the infusion of belantamab mafodotin. For most patients, visits every 3 weeks seem to work out relatively well.

Some patients who are receiving selinexor, even though it is an oral agent, may require additional supportive care measures such as antiemetics, fluids, appetite stimulants, and things along those lines. If you are using the twice-per-week dosing of selinexor, it requires more intensive supportive care early on. That may be an attractive issue or an unattractive issue, depending on those 2 patients for what a patient’s level of risk and tolerance for adverse effects relates to. Many patients may end up receiving both potential options, so it is a matter of how you balance what risks they are willing to accept early on as opposed to later, when the choices may be more limited.

Transcript edited for clarity.

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