Myeloma: Follow-Up and MRD Testing

Ajai Chari, MD:The follow-up for multiple myeloma is pretty well standardized. First, we look for serologic remission with the SPEP (serum protein electrophoresis), the immunofixation, the free light chains, and those patients who have urine protein. So, once we see that the serologies are all converting to negative, ideally, the next thing that should also be considered is imaging, because for the patient who may have presented with a lot of bone disease, we want to make sure that the bone disease is all resolved. And so, this is where PET scans and MRIs are much more useful than X-ray, because once the bone is damaged on plain X-ray, even if the disease is in remission, it may not completely normalize and typically does not—whereas PET scans will go from FDG-avid to FDG-not avid or MRI lesions can improve with treatment.

So, if a patient has serologic remission, radiologic remission, then a bone marrow could be done to determine if a patient is minimal residual disease—negative. And I mention the imaging because the bone marrow is just a random sample, and if you get an MRD-negative result but then the patient still has radiologic disease, that is not the same as somebody who has negative imaging and is MRD-negative. And with the second patient, we’re much more confident that we really achieved a good remission.

So, in the ALCYONE study, it’s impressive because even in an elderly population, almost one-quarter of patients attained MRD negativity. The use of MRD is really important in this type of setting because there’s no need for MRD in a penta-refractory patient who’s heavily pretreated, because you want to see that the overall survival is better, and the progression-free survival should speak for itself. As you move up into these newly diagnosed settings—because myeloma patients are living longer and longer—the follow-up for showing that somebody is MRD-negative, a particular arm is better than another and would be really prohibitively long. And so, MRD can be used as a surrogate endpoint specifically in this kind of newly diagnosed setting or in a maintenance setting, where this is the earliest sign that we’re really going to have impact on long-term outcomes.

Transcript edited for clarity.

• A 74-year-old woman was admitted to the ICU with pneumococcal bacteremia. She complained of recent severe fatigue, loss of appetite, nausea
• History: chronic HTN, aortic insufficiency, diabetes mellitus
• 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, 8.3 g/dL
  • Ca²⁺16.35 mg/dL
  • Creatinine, 1.0 mg/dL
  • Creatinine clearance, 59 mL/min
  • M-protein, 1.6 g/dL
  • B2M, 4.9 mcg/mL
  • SFLC, kappa, 150 mg/L
• Bone marrow biopsy, 70% plasma cells
• Molecular testing, t(4;14)
• ECOG 2