Optimizing Multiple Myeloma Treatment with 4-Drug Regimens


4-drug treatment regimens could provide optimal care strategies for patients with multiple myeloma.

Ryan Haumschild, PharmD, MS, MBA: Ms Maples, we know that anti-CD38 continue regimens are very common. We even saw at ASH [American Society of Hematology] Annual Meeting in Atlanta, Georgia that 4-drug regimens are being evaluated for the use in patients with newly diagnosed multiple myeloma. This includes results from the GRIFFIN trial with daratumumab and the GMMG HD7 trial with cetuximab. How do you evaluate the value of a 4-drug regimen in multiple myeloma?

Kathryn Tyler Maples, PharmD, BCOP: One of the big things that we want to think about, especially in these 2 trials, is we want to make sure that we’re not impacting anything that’s going to impact their transplant. As Mr Hannah mentioned in the beginning, we’re still using transplant as a standard of care for patients with myeloma. When we think about how we optimize and improve on our historical standard of VRd [bortezomib, lenalidomide, dexamethasone] induction, we want to make sure that whatever we add to that isn’t going to impact the patients’ ability to collect stem cells, increase any toxicity going into transplant, or cause any problems post-transplant.

One thing that I took away from these 2 trials is that we didn’t see any negative implications of the patient going to transplant. Patients were still able to proceed with their stem cell collection, get their transplant, and move forward. What we did see in these studies is that the addition of that anti-CD38 increased the depth of response. We’ve talked a lot about MRD [minimal residual disease] negativity, but we don’t know exactly how to use that right now. It’s still mostly being used in clinical trials. However, there was 1 large meta-analysis in recent years that showed MRD negativity does translate into longer progression presurvival and longer overall survival in all our various cohorts with myeloma: newly diagnosed transplant-eligible, newly diagnosed transplant-ineligible, and relapsed/refractory patients. If you’re able to achieve that MRD negativity, it translates into prognosis. Although we don’t necessarily know how to use it to guide clinical practice, the addition of the quad improved MRD negativity rates. With long-term follow up, that should translate into better efficacy and PFS [progression-free survival] rates. It didn’t have any negative implications on their transplant. All those things combined led to a very high favorable use of the quad-based regimens.

Ryan Haumschild, PharmD, MS, MBA: Excellent. I like how you went into a little of the MRD negativity. Because when we think about it, MRD can be an important test in the future of practice. It can also let us know when patients can go off maintenance therapy and potentially be drug-free. That could potentially be an option in the future as well. That’s really exciting.

Ms Maples, how is your practice using MRD testing? How do you expect it will change or be utilized more in the future?

Kathryn Tyler Maples, PharmD, BCOP: That’s a good question. In my practice, we’re mostly using this for information gathering. We use it as part of conversations with patients as well, especially in that maintenance setting. We tend to think lenalidomide is a well-tolerated medication, but it has its downfalls. It can cause some pretty significant fatigue and diarrhea for patients. Some patients would really like to stop their lenalidomide maintenance. MRD negativity is hopefully going to be the tool that helps us have those conversations.

In my practice, we’re getting MRD negativity. When we do, they’re restaging bone marrows each year. We’re using it as conversations to have with the patients where we’re very honest. We don’t know if we can stop your therapy, we don’t know necessarily how to use this test, but we know that it should translate into prognosis. We use that in our conversations. But we have to be mindful that it’s an extra test, it’s costly, and if we’re not going to do anything with the results, we’ve had patients say, “If you’re not going to change anything, then I don’t want to pay for this additional test.” We need to keep that in mind until we know how to use it. The clinical trials are testing MRD negativity at different time points and in different ways, so hopefully we’ll start to learn how to best use it.

Transcript edited for clarity.

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