Insights from Experts at Mayo Clinic on Translating Evidence to Clinical Practice - Episode 6

Case Presentation 2: Transplant-Ineligible NDMM and Treatment With the DRd Regimen

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Experts review a second patient case wherein transplant-ineligible newly diagnosed multiple myeloma was treated with the daratumumab, lenalidomide and dexamethasone regimen and how updated data from the MAIA trial can be incorporated into clinical practice.


Shaji Kumar, MD: David, maybe we can look at one other case.

David Dingli, MD: Thank you, Shaji. This is a patient who I have been seeing for the last 10 months or so. This is a 76-year-old gentleman who presented with worsening anemia that required transfusion as of June of last year. He had worsening back and hip pain with an ECOG performance status of about 3, which was very frustrating for this gentleman who wanted to continue to work and run his business. When I initially saw the patient, he was anemic with hemoglobin of 8.3g/dL. He had mild renal insufficiency with creatinine of 1.86mg/dL. He had normal calcium, marginally elevated LDH [lactate dehydrogenase], and not surprisingly, his beta-2 microglobulin was 13 mg/L. I assessed stage III disease by definition. He had an M spike of 4.7 g/dL identified as an IgG [immunoglobulin G] kappa. He had suppression of IgA [immunoglobulin A] and IgM [immunoglobulin M], and kappa free light chain was 7.73g/dL with a high kappa-lambda ratio of over 300g/dL. His urine protein showed a small amount of kappa free light chain. A bone marrow biopsy showed a lot of disease with 80% to 90% kappa light chain restricted plasma cells, but fortunately he had standard-risk disease with a hyperdiploid clone. We performed a CT scan of the skeleton, which showed a number of lytic lesions and involving a fracture of L4 [vertebra].

This is an elderly gentleman with a poor performance status, transplant ineligible, generally. I offered him therapy with daratumumab, lenalidomide, and dexamethasone as per the MAIA trial. Given the renal insufficiency, I decreased the dose of lenalidomide to 10 mg, and given his age I gave him 20 mg of dexamethasone. In this type of patient, I prefer to err on the side of caution because I think more patients run into trouble because of drug toxicity rather than not controlling the disease in this type of context. I want to emphasize the importance of supportive care. The patient was on acyclovir, trimethoprim, sulfamethoxazole after cycle 1, and this is important, I generally do not give sulfamethoxazole with the first cycle. As we all know, patients can develop a rash with the lenalidomide, and I find it simpler to understand what is what if I don’t have 2 drugs that can cause a rash. The patient started on aspirin for thromboprophylaxis, vitamin D, and calcium supplements, and 1 dose of denosumab. After improvement in kidney function, I switched to zoledronic acid and an analgesic, initially. We proceeded with vertebroplasty to L4 as you can see in the next figure. There is an impending fracture there of L4 with some collapse. I last saw the patient last month. He had received 10 cycles of therapy.

He has had a very nice response. He has a VGPR [very good partial response]. He is transfusion independent with hemoglobin of 11.2 g/dL, and creatinine has improved. He is essentially pain free. His performance status has improved to 0 and 1, and we have achieved his goal. The patient continues to work.

Shaji Kumar, MD: That’s great. I think you highlight some very important aspects in terms of modifying therapy based on the patient status, especially the frailty and the performance status, especially the importance of starting off gently, maybe even starting the 2 drugs and adding the third drug later, depending on the given situation. We have a lot of data with the lenalidomide and dexamethasone [Rd] doublet for a long time. The FIRST trial and the MAIA trial clearly demonstrated an advantage of adding a monoclonal antibody to the Rd combination. Morie, do you want to speak about the MAIA trial results?

Morie Gertz, MD: I will. First, I have 2 questions I want to ask. No. 1 is, of the 4 of us, for newly diagnosed myeloma, does anybody use a fluoroquinolone for the first couple of cycles of therapy based on the MRC trial data? No. 2, is this patient transplant eligible now?

David Dingli, MD: I did give the patient levofloxacin. Is the patient transplant eligible? Functionally, he has improved. He has achieved a VGPR. Technically, he can probably go through transplant safely. I think we have shown in our series that patients up to the age of 79 probably can be transplanted with very similar outcomes. It becomes a bit of a philosophical choice whether the patient is willing to sacrifice a few months of his life to be away from home, perhaps potential short-term toxicity related to the transplant, or continue on this therapy the patient is tolerating well. I do not know if there is a right or wrong answer for that.

Shaji Kumar, MD: I was going to ask you that question. If you take this patient to transplant, I know age is no bar….

Morie Gertz, MD: Age is no bar, it’s performance status. And at a performance status of 3, that patient is not a transplant candidate. We have done transplants in 60 patients over the age of 75, and it’s no mortality. Of the patients we have selected to transplant, that transplant-related mortality, day 100 all cause, is zero. It’s only 60 patients, of course, and the results may be different with 400. This patient is VGPR, and I understand he is 76, but maybe we can get him to stringent complete response and get him MRD [minimal residual disease] negative. I also would have given him a fluoroquinolone.

Shaji Kumar, MD: This case illustrates why we don’t want to make that determination of transplant eligibility right in the beginning, and instead wait for a couple of cycles for the disease to respond, and have all those disease-related adverse effects or comorbidities out of the way before we make that decision with transplant. You were going to talk about the MAIA study results.

Morie Gertz, MD: The MAIA study built on the Rd doublet and took patients who were firmly transplant ineligible—recognizing that this is a European trial and the definition of what's transplant eligible is very different. But having said that, the MAIA trial consisted of almost half the patients over the age of 75. This was an older group with a significant number of frail patients, and it was daratumumab-Rd versus Rd. Other than a slight increase in respiratory infections as the only toxicity, the daratumumab-Rd did well, and they achieved 14% MRD negativity. This result, without transplant, is very impressive. It still doesn't answer the question of a quadruplet versus triplet because you could argue if, even in a frail patient, is there a role for daratumumab-VRd [bortezomib, lenalidomide, dexamethasone] lite? Of course, that hasn't been looked at, it hasn’t been studied, but I don’t want to suggest that daratumumab-Rd is the only appropriate consideration for the frail elderly.

Shaji Kumar, MD: It’s quite interesting that the median PFS [progression-free survival] with MAIA is almost the same as what you would see with a 3-drug induction, transplant, and lenalidomide maintenance of almost 5 years. Certainly, it brings up that discussion with the patient. I think you alluded to the question of whether the patient would want to go through that.

Transcript edited for clarity.