Unmet Needs in High-Risk Multiple Myeloma

C. Ola Landgren, MD:For patients who present with a new diagnosis of myeloma with high-risk features, what are the unmet needs? I would say that the unmet needs are unlimited. The reason I think that is because the therapies that we use for patients who present with a new diagnosis of myeloma are typically the same across the board. A new diagnosed patient gets the proteasome inhibitor, usually with an immunomodulatory drug and steroids. Or there’s renal insufficiency, and in that case the immunomodulatory drug is commonly used, the patient is switched to Cytoxan.

Now, patients with high-risk disease, we know that they very commonly do respond to these different types of combinations of therapy. But unfortunately, we also know that they’re more prone to relapse, and it can happen in 6 to 12 months. If the patient goes forward with a transplantation, usually that works out well. But, again, the relapse could come 6 to 12 months after the transplantation. The patient chooses to go on combination therapy and go straight to maintenance. Because he or she is not a transplant candidate, unfortunately, the relapse could come 6 to 12 months later.

So, I think we are at the juncture right now in the field, treating myeloma, where we see major, major advances in the outcomes for the patients in general. We see patients diagnosed with myeloma with standard risk having maybe 10, to up to 20, years of projected overall survival, which is fantastic. And during those 10 to 20 years ahead, there probably would be very many new drugs developed so patients potentially could live with the disease as a chronic disease and ideally maybe some patients cured even.

But at the same time, we have those patients who present with a very aggressive biology. They probably represent 10% to 15% or so of patients. We still give them the same therapy, because that’s the best we have. And as I pointed out, unfortunately they relapse. So, the needs are enormous here. We really need to further understand the biology of these high-risk cases, probably carve out subtypes—I would think there is more than 1 type that falls into this category of high-risk disease—and try to use insights from biology to develop new treatments. And also, empirically to use new drugs to see if they can overcome the high-risk features of relapse and shortened survival.

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