Prognosis and Standard Treatment for AML-MRC

Harry Erba, MD, PhD:This patient has a number of poor-risk features that have been associated with a worse survival: age over 60 and the cytogenetic changes. In patients with AML with a history of MDS or therapy-related changes or other myelodysplasia-related changes, other than the morphologic dysplasia, the survival, even with intensive chemotherapy, has been around 20% at 5 years, and that comes from a large Swedish registry with median survivals of less than a year.

You have to clearly understand the goals of your treatment when you approach a patient such as this. This is a 68-year-old man who has just recently had myocardial infarction who has very poor-risk AML based on the deletion 5q and myelodysplasia-related changes. The only potentially curative option for this patient is going to be allogeneic stem cell transplant. Chemotherapy may induce a remission, but it won’t be durable. He has recently had an MI and we have to see how he recovers from initial therapy. So, you may not have to actually make that decision right then about whether the patient is going to be eligible for allogeneic stem cell transplant. You have to first get that patient into a remission.

So, what are the options for remission induction chemotherapy according to the NCCN? If we take the subset of patients who are over the age of 60 with poor-risk AML, defined as myelodysplasia-related changes, then there are a number of options. Until recently, 7 + 3—7 days of cytarabine, 3 days on an anthracycline, gemtuzumab ozogamicin, the anti-CD33 immunotoxin—has been actually FDA approved for AML based on the French ALFA-0701 study, showing an improvement in event-free survival when gemtuzumab was added to chemotherapy in patients between the ages of 50 and 70, like this patient. So, you can consider adding gemtuzumab to 7+3.

On the other hand, for this group of patients, you could use hypomethylating agents as well—azacytidine or decitabine. And then finally, liposomal daunorubicin/cytarabine, this patient has AML with myelodysplasia-related changes and would be eligible for that therapy.

So, in thinking about how I would select the most appropriate induction therapy, I think the following would be considerations. First of all, his white blood cell count is high. And in my experience and if you look at the literature, hypomethylating agents are not very effective at controlling a hyperproliferative acute myeloid leukemia. And so, if the patient is eligible for chemotherapy, I really would not be thinking of a hypomethylating agent in that situation.

And so, then the decision comes down to 7+3, with or without gemtuzumab, versus liposomal daunorubicin/cytarabine. Well, given that he has an unfavorable karyotype, the subset analysis of the ALFA-0701 study showed no benefit of adding gemtuzumab to chemotherapy in that subset of patients. No improvement in CRs or event-free survival or overall survival. Added to that, the fact that even at the lower dose of gemtuzumab that we’re using now—3 mg/m²on days 1, 4, and 7 with 7+3—there’s still a risk of being an occlusive disease, and in a patient who may ultimate have a transplant, that may be a potential concern. So, I would not use gemtuzumab in this situation.

So, then the decision really comes down for this patient between using standard 7+3 or the liposomal formulation of daunorubicin and cytarabine. However, if he gets to a remission, the only potentially curative option if he’s eligible will be an allogeneic stem cell transplant.

Transcript edited for clarity.

Case: A 68-Year-Old Man With Newly-diagnosed AML

• A 68-year-old man went to the emergency room with complaints of dizziness and chest pain
  • Myocardial infarction diagnosed and managed in hospital
  • During stay, CBC revealed decreased neutrophils but increased total white blood cell count
  • When stable from MI, he was referred for specialist consultation
• Patient history and physical exam:
  • Reported fatigue, shortness of breath with minor exertion, and unexplained weight loss that have worsened over the past 2 months
  • Over the 6 months, has experienced three upper respiratory infections, often with mild fever, that were refractory to treatment, but which he attributed to being a former smoker
  • No history of cancer or cytotoxic treatment
• Laboratory findings:
  • Absolute neutrophil count: 600 cells/µL; WBC: 85,000 cells/µL
  • Peripheral blood shows poorly differentiated myeloid cells
  • 25% blasts in peripheral blood
  • Cytogenetic abnormalities: chromosome 5 (del[5q])
• Diagnosed with acute myeloid leukemia with myelodysplastic-related changes
• Received Vyxeos (CTX-351) induction therapy, followed by consolidation
  • Experienced complete response and underwent HSCT