Video
Clinical Case 2: 59-Year-Old Woman With R/R MM
Author(s):
Experts in hematology-oncology review the case of a 59-year-old woman with relapsed/refractory multiple myeloma and discuss their thoughts on the given treatment approach.
Nina Shah, MD: We’re going to move on to the next module, which is “The Current and Future Role of Antibody-drug Conjugates in Relapsed and Refractory Multiple Myeloma.” For this, we’ll present another case. This is a 59-year-old previously healthy woman who’s found to have symptomatic IgG kappa multiple myeloma presenting with both R-ISS [Revised International Staging System] stage III and ISS [International Staging System] stage III. She presented with hypercalcemia and anemia. She had a normal LDH [lactate dehydrogenase], but had deletion 17p in 65% of her bone marrow plasma cells. Her PET [positron emission tomography] CT also showed lytic lesions. Otherwise, her past medical history is unremarkable.
Up front, she received daratumumab-RVd [lenalidomide, bortezomib, dexamethasone] induction therapy, went on to high-dose chemotherapy and transplant, and thereafter received lenalidomide maintenance. About 2½ years later, she had a serologic progression and then was found to have new lytic lesions. She had gotten 4 prior therapies because she had gotten a quadruplet—which included an anti-CD38 monoclonal antibody, the PI [proteasome inhibitor], and an IMiD [immunomodulatory imide drug]—therefore, her physician recommended starting her on belantamab mafodotin. She underwent evaluation by an ophthalmologist prior to initiating belantamab and was found to have good eye health. Fourteen months into treatment with belantamab, she’s tolerating the treatment well and is active.
I want to go around and see if each of you would agree with this treatment approach, and why or why not. I’ll start with you, Josh.
Joshua Richter, MD: Based on the available data, it’s a reasonable approach, especially having lost 2 drugs in 2021 that could have played a role in this space, between melphalan flufenamide and panobinostat. Most of us would seek some type of clinical trial for this patient. There are a number of clinical trial assets, ranging from CELMoDs [cereblon E3 ligase modulators] to bispecifics and CAR [chimeric antigen receptor] T cells. However, if the patient wasn’t eligible or didn’t have access to that, we understand that BCMA is a key target in the relapsed setting. It’s a great option, although other options by clinical trial may be better.
Nina Shah, MD: Great. Ola, would you have agreed with this approach that the physician took?
Ola Landgren, MD, PhD: First, I agree with Josh. I’d look for a clinical trial. The bispecifics would be very attractive, CAR T cells could be very attractive, and CELMoDs for sure. Looking at the case in a little more detail, it’s a young patient. The report says 65% of her plasma cells have 17p deletion. We don’t know what the other allele entails, whether there’s a mutation. Then we see that there’s all the bone disease and the patient relapses after 2½ years, so it makes me believe that this is probably really bad disease, with 17p deletion and probably a mutation on the other allele. Here we are after 4 drugs with more bone disease and progressive disease.
I would have probably considered some of our old-school chemotherapy to debulk. My go-to would probably be DCEP [dexamethasone, cyclophosphamide, etoposide, cisplatin] therapy. I would check the bone marrow to begin with, and if I saw 90% myeloma cells there, I’d definitely debulk with DCEP [dexamethasone, cyclophosphamide, etoposide, cisplatin]. I’d offer the patient outpatient treatment with DCEP [dexamethasone, cyclophosphamide, etoposide, cisplatin] and have the patient come in every day for 4 days in a row and swap the cassette. I’d check in the outpatient setting. I typically do blood work Mondays and Thursdays and blood or platelet transfusion Tuesdays and Fridays.
After 2 weeks, you’re usually out of the woods. I’d do a new bone marrow again, and if they went from 90% to 40%, I’d tell the patient, “This seems to have worked, but there’s more disease left,” and I’d offer another DCEP [dexamethasone, cyclophosphamide, etoposide, cisplatin], recognizing that’s a tough ride. Then I’d probably put the patient on some other outpatient combination therapy that we can discuss. I like to use the CYKLONE [cyclophosphamide, carfilzomib, thalidomide, dexamethasone] therapy that Keith Stewart used, the carfilzomib-Cytoxan-dexamethasone with or without low-dose thalidomide. I heard Sagar say that Cytoxan should go. I think it has a role in patients with dire disease in the absence of other approved drugs.
Nina Shah, MD: Sagar, you’re next. Would you have taken this approach or another one?
Sagar Lonial, MD, FACP: We all have an interest in enrolling patients on trials. Ola’s description of DCEP [dexamethasone, cyclophosphamide, etoposide, cisplatin], whether it’s in or out, to me is a last-ditch effort. I save that for when the blood counts are low and I don’t have many other options to give. Belantamab mafodotin is a reasonable thing to give this patient. We talk about the approved drugs in triple-class refractory myeloma. Almost all of them require pretty significant supportive care and multiple visits to the clinic in between doses of drug. With belantamab mafodotin, you come once in every 3 weeks, and once you get your ophthalmologist set up, it’s relatively easy for patients to do. Other than the keratopathy, which I’m sure we’ll talk about in a few moments, it’s tolerated pretty well by most patients. It’s a reasonable thing to do, also knowing that you can come back with another BCMA-targeted agent should that become available as you need down the road.
Nina Shah, MD: Good point. Katja, would you have done this for this particular patient?
Katja Weisel, MD: I couldn’t, so I wouldn’t have considered it. We need at least 3 lines and highly refractory status. I wouldn’t have necessarily considered this patient anti-CD38 refractory, or PI refractory, because there was the autologous transplant and the lenalidomide maintenance in between. Because we can’t go to an anti-BCMA in Europe except on clinical trials, we probably would have used isatuximab–Kd [carfilzomib, dexamethasone], switch the anti-CD38 off, and go on a pomalidomide-based regimen.
We also love the pomalidomide-cyclophosphamide-dexamethasone, and we go back to cyclophosphamide in a case where we have a highly aggressive disease in a young patient, like when the bone marrow is totally full. I agree with Ola that sometimes we salvage those patients. We normally use that inpatient because we can’t handle it outpatient and we use the PACE [cisplatin, doxorubicin, cyclophosphamide, etoposide] regimen, or modified PACE, in such distant situations. This would have been my approach. However, I agree with what Sagar said. Belantamab mafodotin is easy to use to go for an anti-BCMA strategy, which is an imminent goal in such a patient, to go as early as we can.
Nina Shah, MD: Those are all good points. You remind us that not all people can practice the same way everywhere, which is important to keep in mind.
Transcript Edited for Clarity
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