Transplant and Unmet Needs in Myeloma

Ajai Chari, MD:In terms of the role of autologous transplant in high-risk patients, it’s a very difficult question to answer, because high-risk patients probably make up about one-third of newly diagnosed patients. And so, that means that when we do clinical trials, only one-third of the patients will be high risk in the 2 different arms. So, we really can’t power studies to definitively answer this question, and also there’s the logistics of screening a patient and enrolling them and then finding out their molecular risk after the fact.

I think the current thought process in myeloma is that everybody benefits from induction therapy and consolidation with transplant, based on aNew England Journal of Medicinepaper the French presented showing that an early transplant leads to significant prolongation of progression-free survival by almost 14 months relative to delayed transplant. Then the question is, of course, maintenance therapy, and also who’s the candidate for transplant. So, for high-risk patients, we know that even with good induction therapy and transplant, they will relapse sooner, and so there’s work being done on more aggressive maintenance therapy beyond just a single agent. And there are some preliminary data showing that double-agent therapy might be better.

For this particular patient, of course, the question is, is she eligible for transplant? And that’s a difficult question. It really depends on the cancer center and where the patient is being diagnosed and treated. Medicare pays for transplant up to age 80. However, because we need to reduce the dose of melphalan-conditioning chemotherapy for transplant, anybody over the age of 70 is going to get a slightly lower dose of the chemotherapy. And given all of the exciting drugs that we have now at our disposal, the risk/benefit ratio may be slightly different. And so, many patients above the age of 70, if they have a good response to the initial therapy, may not necessarily benefit from transplant. But, again, the data for this particular subgroup are limited in the era of current modern therapy.

I think the unmet needs in multiple myeloma in general are frail, elderly patients who are often not enrolled in clinical trials. Second would be renal insufficiency, and the third is high-risk patients, because those are the 3 groups of patients who are probably bringing down the median overall survival curves. And so, if we could improve the outcomes of these patients, I think we would then make the entire disease look better, because it’s not just the selected, cherry-picked young, fit patients who are really perfect. And the reality is that myeloma is often a cancer of the elderly with a median age of 65, although at our institution, our youngest was diagnosed at 18 and the oldest is over 100. So, when you have such a heterogeneous disease, we really have to be mindful of personalizing the therapy for that patient. And so, for this patient particularly being high risk, it’s really important to be aggressive with therapy because in older patients, often you don’t have as many chances to salvage because of their comorbidities. You have 1 good shot to get their disease under control.

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