Myeloma: Impact of the ALCYONE Trial

Ajai Chari, MD:There is a recently published study in theNew England Journal of Medicinecomparing VMP with daratumumab/VMP. And the reason this is an important study is that historically, there’s this perception that elderly patients cannot get more than 1 drug because they’re going to have more toxicity. But I think we have to be mindful again of what drugs we’re talking about. If you combine drugs with overlapping toxicity, you’re going to have more side effects. And so, VMP—which is not as widely used in the United States, but it’s a very widely used regimen globally—basically is bortezomib/melphalan/prednisone, and that was already shown in the VISTA study to be superior to melphalan/prednisone (MP), which is an oral doublet regimen.

So, we know that VMP resulted in better overall survival than MP, so the question is, can we now further improve upon VMP? And in this randomized study, transplant-ineligible patients are randomized to either VMP or the addition of daratumumab in standard dose and schedule. And so, what this study showed is that, very impressively, all of the efficacy endpoints were met. So, we saw improvement in response rates, improvement in CR rates, improvement in MRD negativity, and an improvement in progression-free survival. These are really encouraging data for a population, as we had said, that is historically an unmet medical need, which is the elderly patient population. So, to see improvements in outcomes in this population is really exciting.

For this ALCYONE study, when we compared daratumumab/VMP with VMP, the safety was also very encouraging in terms of that really, there were no significant differences in cytopenias. And the main difference was that there was a slight increased rate of infection. But, again, this is an elderly population with a lot of comorbidities. Infections are very common in myeloma, but I think it does bring to mind that we need to be very aggressive with elderly patients in terms of supportive care like growth factors, antibiotics, and, potentially, the use of intravenous immunoglobulin if somebody is very hypogammaglobulinemic.

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