Patient Case 3: Relapsed/Refractory Multiple Myeloma

Expert panelists center discussion on a final patient case to review the identification and management of relapsed/refractory multiple myeloma.


Beth Faiman, PhD, MSN, APN-BC: The next segment focuses on BCMA therapies. I’m excited because when I first managed myeloma years ago, my colleagues heard about my sad stories of thalidomide before we had a REMS [risk evaluation and mitigation strategy] program and high-dose dexamethasone to treat amyloidosis. Now we have so many advances in therapies. We’re going to dive into the final case study, focusing on a newly diagnosed patient who—starting in 2014—presented to a primary care provider with mild anemia. Further work-up showed that she was not iron deficient. The MCV [mean corpuscular volume] was about 90 μm3, so you’re thinking anemia, chronic disease. You do the anemia work-up, but it didn’t identify anything. They ran a SPEP [serum protein electrophoresis], which showed an M-spike [monoclonal protein] of IgG kappa. The M-spike was low, 1.5 g/dL, so it was referred to hematology. Because of the anemia, they saw Dr [Sandra] Mazzoni, who specializes in benign hematology and myeloma. Unfortunately, after some time of monitoring for MGUS [monoclonal gammopathy of undetermined significance], progressive smoldering myeloma, a bone marrow biopsy eventually shows 60% kappa-restricted plasma cells. The good thing is that this individual had standard-risk disease, no gain of 1q—I always add 1q because it’s not really in the high-risk category. Dr Khouri, is amp 1q or gain 1q a high risk?

Jack Khouri, MD: Gain 1q plus 1q is a high-risk feature. It wasn’t part of the revised ISS [International Scoring System], but large clinical trials have looked at patients with plus 1q abnormalities, and the addition of an extra copy of the chromosome 1q is a high-risk feature. There are different categories of plus 1q. There’s gain 1q and amplification 1q, depending on how many copies you have. Amp 1q seems to be worse than gain 1q, but an extra chromosome 1 is definitely a bad thing.

Beth Faiman, PhD, MSN, APN-BC: Absolutely. I think we all agree. Also, did not have any deletion of 17p, 4;14, 14;16, and just to be clear for the audience, we mentioned in a previous case study translocation 11;14, it’s not a negative prognosticator. Dr. Williams, what are your thoughts on 11;14?

Louis Williams, MD: 11;14 is not a high-risk cytogenetic abnormality. It confers an overexpression, so it’s often accompanied by a CCND1 mutation. This confers more of a B-cell phenotype and high levels of BCL2 expression. It’s possibly a more lymphoma-like myeloma. The big news in recent years is that we’ve been able to target these t(11;14) patients with venetoclax at various times during their treatment. There are 1 to 3 lines of therapy, as done in the clinical trials, but there are many concepts under development.

Beth Faiman, PhD, MSN, APN-BC: The BELLINI study randomized patients. When it was underway, there was such a poor outcome. The study was halted because patients were dying. Then on the subgroup analysis, it was 11;14 patients. Dr Mazzoni, any thoughts on 11;14? Would you go to a venetoclax earlier in the second or third line outside a clinical trial? Are there any agents that you’re aware of that are under investigation?

Sandra Mazzoni, MD: There are agents under investigation. We have 1 of those studies at our institution right now. The role for venetoclax, especially for those who aren’t transplant eligible, is that I use it in the second line…. That gives them another oral option. They do really well. With some of these patients I’ve run into cytopenia issues with IMiDs [immunomodulatory drugs], and I don’t have that problem with venetoclax. I can get away with venetoclax-dexamethasone, and they respond beautifully.

Beth Faiman, PhD, MSN, APN-BC: Even at 100 mg in some of these patients, you had quite a few success stories in 50 mg.

Jack Khouri, MD: I tend to go to the first relapse, but some analyses show that a good number of t(11;14) patients respond to the daratumumab. Then you do venetoclax in the third-line setting, and they respond beautifully.

Beth Faiman, PhD, MSN, APN-BC: Going on with the case study, this patient has high M-spike. They developed MRD [minimal residual disease]–negative status but declined a stem cell transplant because their aunt had 1 for lymphoma and didn’t do well; we hear that from time to time. They decided that because they had an awesome response, they didn’t even want to go on, let alone on maintenance. The [Philip] McCarthy meta-analysis suggested that patients’ had an overall survival advantage. What are some of the continuous maintenance therapies? Let’s say that this individual had VRd [bortezomib, lenalidomide, dexamethasone] induction. Would you de-escalate therapy, after they have their nice response? Let’s say you get 6 cycles of the V [bortezomib] and then the lenalidomide and dexamethasone are well tolerated. Would there be a reason to de-escalate therapy, or do you continue that same therapy? Continuous vs maintenance is a big discussion these days.

Sandra Mazzoni, MD: The pivotal point is how well of a response they get. Do they get to a CR [complete response]? If they’re still sitting at a VGPR [very good partial response], maybe push them out and get a year of triplet therapy and then move them to a maintenance.

Beth Faiman, PhD, MSN, APN-BC: This individual had a nice MRD-negative status, declined stem cell transplant, and was off therapy for about 4 years. This was excellent for their quality of life. They were able to do things they wanted to. Unfortunately, they started to have this low biochemical disease progression with increasing monoclonal proteins. We know the criteria for disease relapse is the 25% increase, accompanied by another 25%. What about MRD-negative patients? Do you do a subsequent evaluation outside a clinical trial? If they lose the MRD-negative status and standard-risk disease, do you wait until they have biochemical relapse in the serum and urine? What are your thoughts on changing?

Jack Khouri, MD: We still don’t know how to approach MRD in the real-world setting. A bunch of clinical trials are testing this. I’ve checked MRD status on patients after they’ve been on maintenance for quite some time, to see if we can de-escalate. So far, my patients are doing well. In the real-world setting, many people are doing that, but we’re waiting on clinical trials for a more guided strategy.

Beth Faiman, PhD, MSN, APN-BC: It’s nice to know but we don’t need to know. You and I have shared patients who have been on lung maintenance for 13 years. At what point do you decide it’s time? Have you had experience with that?

Louis Williams, MD: Yes, in 13 years of lenalidomide maintenance, I didn’t worry about secondary malignancies. The percentages are low initially in the first 5 years, but you get these individuals who have excellent outcomes from their myeloma. It would be an interesting thing to look at MRD in those settings. Do you need the lenalidomide at 13 years out? I’m not sure.

Beth Faiman, PhD, MSN, APN-BC: In my experience, we had the SWOG S0232, which was a Jeff Zonder study from 2002. We have some patients who are still on it. Is it 20 years too long? It’s too long to stop, and the patients are comfortable staying on.

Transcript edited for clarity.

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