Myeloma: Risk Assessment and Therapeutic Approach

C. Ola Landgren, MD:When we have a patient with myeloma presenting with symptoms like this case, we are asking ourselves, and the patient is asking, what’s the risk? What’s my prognosis? There are different ways of looking at that. The initial idea goes back to the 1970s where people thought that maybe stage would be relevant. But I think there is mounting evidence that the stage is probably less important, that rather the biology of the cells is more important.

The best technology that’s widely available at this time is still the FISH and cytogenetics. And this is about to change. We are seeing a lot of new technology coming out, and I think we soon will see DNA-based sequencing where you capture gains and losses and translocations, as well as somatic mutations. But for now, FISH and cytogenetics is the most commonly used tool.

This particular patient had a 70% plasma cell infiltration of the bone marrow with kappa light chain—restricted plasma cells. And the FISH report shows that there are 17p deletions. 17p deletions are known to be probably the most aggressive biology. There are a lot of details to 17p deletion, and that’s true for the other changes as well that you can pick up with FISH and cytogenetics. For example, do all the plasma cells have 17p deletion or is it the small proportion? Are we talking 10%? Are we talking 95%? We only know from the report that the majority of the cells have it. So, we don’t have an exact number but we have an indication from the report that the majority have it.

Another variable is whether both of the alleles are impacted. We all have 1 allele from our mother and 1 from our father. If both of those alleles have been deleted, we’re actually talking about the double-head of 17p. That we don’t know, because FISH and cytogenetics would not capture that. You would need to have a DNA-based assay, and they are not yet implemented in clinical practice. So, to summarize, the patient has a 17p deletion reportedly in the majority of the cells. These are high plasma cell infiltration of the bone marrow, and she presents with kidney failure. I would say that this is a high-risk patient for these reasons. The stage is not defined because we are lacking information from the workup. But stage, in my opinion, is probably less important for clinical management.

When it comes to treatment of this patient, there certainly are several options to consider. This is typically the case for most patients who present with a new diagnosis of myeloma. Looking at the current literature, most doctors would probably agree that a 3-drug combination is the preferred way to go. Looking at international guidelines for patients who do present with kidney failure, the guidelines state that the use of a proteasome inhibitor would be considered to be standard, in combination with a steroid. And also, the international guidelines would say that the addition of Cytoxan (cyclophosphamide) would be recommended if that could be given. Both proteasome inhibitors, Cytoxan and also dexamethasone, are considered to be kidney safe, so you don’t have to worry about patients’ underlying kidney insufficiency in this case. So, I think the practical implications for this patient would be to consider, for example, bortezomib with cyclophosphamide and dexamethasone, which would be a very appropriate therapy.

In the event that the patient could not receive Cytoxan, I guess you could give bortezomib (Velcade) and dexamethasone alone. It would certainly be less efficacious, and it would take longer for the patient to respond and obtain a deep response. And I don’t really see, based on what we know, that there’s a reason to not give the Cytoxan. I’m sure there are doctors who would consider using carfilzomib with Cytoxan and dexamethasone in a patient with renal failure. But given that the patient has an underlying cardiovascular history, I think it probably would be a safer strategy to use the bortezomib with Cytoxan in this case.

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