Case-Based Overview: Newly Diagnosed Multiple Myeloma

Melissa Alsina, MD:Today we are going to discuss the case of a 75-year-old patient who presented with about a month history of severe back pain, intractable to pain medications. She had an MRI [magnetic resonance imaging] of the spine and was found to have multiple compression fractures in the lumbar spine.

Further work-up with a CBC [complete blood count] shows that she was anemic with a hemoglobin of 10.5 g/dL. The CMP [comprehensive metabolic panel] showed a normal calcium level and a creatinine level of 1.7 [mg/dL]. Electrolytes were unremarkable. Further work-up showed that she had a serum protein electrophoresis that was negative with no M-spike, but serum-free light chains were elevated with a kappa of about 1000 and lambda 1, making the ratio of 2000.

This was suggestive of multiple myeloma. She had a bone marrow biopsy, which showed 25% cellularity and 80% plasma cells. Cytogenetics were 46,XX and she did not have any abnormalities by FISH [fluorescence in situ hybridization]. She also had a bone survey that showed multiple lytic lesions in multiple bones and her spine.

Her beta-2 microglobulin, which was done first day here, was 4.7 [mcg/mL], and she had an albumin of 3.9 [g/dL]. In summary, this is a 75-year-old woman recently diagnosed with multiple myeloma. She would be Durie-Salmon stage IIIa, and she would be International Staging System 2 [ISS 2]. The patient clearly needed treatment because she had myeloma bone disease, she was anemic, and she was started on Velcade [bortezomib], Revlimid [lenalidomide], dexamethasone, and daratumumab.

In summary, this is a 75-year-old woman with recently diagnosed Durie-Salmon stage IIIa, ISS 2 multiple myeloma. The patient did not have any comorbidities, so she clearly needed treatment. Initially, she was thought to be a transplant candidate [because of] her performance status, and she was started on Velcade, Revlimid, dexamethasone, and daratumumab. The selection of this treatment was probably based on recent data, showing that that combination of 4 drugs is a very appropriate and very effective combination for transplant-eligible patients, based on a recent GRIFFIN study.

The criterion that we would use to define if a patient is transplant eligible is usually more physiological age rather than chronological age. That’s probably the No. 1 point. We evaluate all the patients who are potential transplant candidates and evaluate their past medical history—their performance status, their comorbidities—and then make a decision based on that.

A minority of the patients are transplant candidates because for myeloma, the median age at diagnosis is 70, so the majority of the patients are older and have multiple comorbidities. A small percentage of patients are actually true transplant candidates, and an even smaller percentage actually have access to transplant.

The role of transplant in myeloma is still very important, despite the fact that we have newer therapies for induction that increase the rates of complete remission. Most studies that have looked at those therapies looked at induction for a few cycles followed by transplant consolidation, followed by maintenance therapy. We get that deep response after transplant consolidation and into maintenance. Transplant still remains very important in myeloma, and I think further studies would have to be done comparing these 4-drug combinations with a transplant arm to really see if that would make a difference if you keep the patients on this drug for a long time. A different question would be patients, for example, who are able to achieve a stringent complete remission with induction, let’s say with 4 cycles of Revlimid, Velcade, dexamethasone, and daratumumab. However, that’s a minority of the patients.

Transcript edited for clarity.

Case: 75-Year-Old Woman with Newly Diagnosed Multiple Myeloma

History and Presentation:

• 75-year-old woman; diabetic on metformin, no history of coronary artery disease or other comorbidities
• κ light chain multiple myeloma diagnosed November 2019
  • Durie-Salmon Stage IIIA, ISS Stage 2
  • Laboratory findings
    • Total proteinuria 5.82 g/day
    • Bence Jones protein (BJP) 3.6 g/day
    • Hypogammaglobulinemia
    • Albumin 3.9 g/dL
    • β2-microglobulin 4.7 mg/L
    • Creatinine 1.7 mg/dl
    • No paraprotein peak but kappa light chain 2000 with lambda light chain at 1
    • Kappa/lambda ratio=2000
• Bone marrow biopsy
  • Cellularity 25% with 80% plasma cells
• Cytogenetics 46, XX
• FISH no abnormalities
• Imaging
  • Skeletal survey: extensive lytic bone disease with healing fractures of left 7^thand the 8^thribs
  • MRI of the spine: multiple compression fractures
  • MRI of the pelvis: diffuse marrow infiltrative changes due to myeloma
• Cytogenetics/FISH: no adverse cytogenetics
• ECOG PS: 1
• Patient was started on D-VRd