Follow-Up and MRD Testing in High-Risk Myeloma

C. Ola Landgren, MD:Typical monitoring for patients who undergo therapy for multiple myeloma include blood work and urine testing, and usually it’s done every cycle. So, at the end of the cycle, blood is drawn and a urine test is done, and the results are being reviewed before the initiation of the subsequent cycle.

In my practice, if I have a 4-week schedule, for example, I would think of doing the therapy. If the dosing is the first 3 weeks and the fourth week off, I usually would draw the lapse in the end of the third week and spare the patient from having to come in and do blood work. It certainly could be done during the fourth week, but I would give my patients a break from coming into the clinic.

When they come back on day 1 of cycle 2, we would review those results—they would all be back—and we would make sure that everything looks good, it’s safe to proceed, and we also see if there is evidence that the therapy works. And then I would repeat that again. If I have a 3-week schedule and the dosing is every 2 weeks and the third week is off, again, I would typically, in my clinic, do the labs at the end of the second week. I would do it the last day of infusions or injections for that regimen and spare the patients from coming in during the off week. It could certainly be done that off week, and probably the results were slightly better because you have another week to wait for the efficacy of the drug. But I do that to save the patients from coming in from additional visits.

When the patient has been monitored over several cycles and you see that the protein’s clear, if there is no monoclonal protein, the light chains are gone. If it’s light chain—secretory disease, the guidelines would say that to confirm a complete response—in this case, I suspect it would be a complete response—you would have to do a bone marrow biopsy.

In my practice, I would typically give patients 6 cycles of combination therapy if they are candidates for transplantation. I would, at the end of those 6 cycles, do a bone marrow biopsy. I would use that to guide the therapy to mobilize the stem cells, whether it can be done with GCSF and plerixafor (Mozobil) or if you need to use cyclophosphamide, for example. So, I start off with the bone marrow blood test and I check the blood and the urine every cycle. In the end, after 6 cycles, I do that biopsy. Because I have the biopsy done to determine the protocol for mobilization of stem cells, I now have access to the bone marrow, and I would always use that for MRD testing in patients who are in a complete response.

At our institution at Memorial Sloan-Kettering Cancer Center for 2-1/2 years, we have set up flow cytometry-based single-tube 10-color with the sensitivity of 1 cell in 100,000 for MRD, and we use that as our standard of care.

We also, since about a half-year back, in parallel with the flow cytometry assay, have a VDJ sequencing—based assay so we can also track molecularly for MRD, and that has the sensitivity of 1 cell in a million. And both these tests are part of our standard-of-care profile in our pipeline. So, we offer this to every patient that comes. For patients who are not transplant candidates, we would offer them to do a bone marrow biopsy. If they continue to receive combination therapy and they are clearly in the blood with a suspected CR, or if they go on maintenance, we would do the same.

The case we discussed today is a 74-year-old woman who presents with a new diagnosis of myeloma. As we discussed, there are so many different treatment options, and also there are a lot of things that are changing in terms of the workup and the prognostic tools we have access to. We didn’t spend very much time talking about imaging, but I think there is going to be new imaging beyond all of the new tests in the blood and the bone marrow. There will also be new MRD tests, probably in the blood. In parallel to this, there are very many new drugs in development—maybe not for a 74-year-old patient—like CAR T-cell therapies. The first therapy we’re thinking of giving the toxicity profile. But there are very many other drugs in development. We have the bispecific monoclonal antibodies. There are drug conjugates that are linked to the antibodies, and there are also many small molecules.

My projection is that we probably will see maybe 5 new drugs approved for the treatment of myeloma in the coming few years. And I’m convinced that with all of the new drugs that we already have and the drugs that are in the pipeline, we will continue to see high rates of minimal residual disease negativity, and that will continue to drive MRD negativity also from a regulatory perspective. I think within a few years, the FDA will accept MRD as a regulatory endpoint for drug approval, and that will just continue to speed up drug approval. There will be many more drugs approved in the coming few years, and these are all great news for our patients.

Transcript edited for clarity.

• A 74-year-old woman presented with anemia, proteinuria, renal insufficiency, and pain in her right hip
• History: chronic HTN, aortic insufficiency, diabetes mellitus
• ECOG performance status, 1
• X-Ray of the pelvis showed numerous lytic lesions in the ilium and a large lesion in the right proximal femur
• MRI confirmed a 9-mm lesion in the right femoral head and numerous bilateral T1 hypointense and T2 hyperintense lesions in both iliac region
• Laboratory results:
  • Hb, 10.1 g/dL
  • Ca²⁺3.32 mmol/L
  • Creatinine, 1.9 mg/dL
  • Creatinine clearance, 30 mL/min
  • M-protein, 1.4 g/dL
  • B2M, 4.9 mcg/mL
  • SFLC, kappa, 150 mg/dL
• Bone marrow biopsy, 70% plasma cells
• Molecular testing, del17p