Treatment Options and Care for Patients Who Develop Therapy-Related AML - Episode 4

Determining the Treatment Options for t-AML

Rami Komrokji, MD:In general, the treatment options are based on several things—the disease itself and the patient’s age, performance, and comorbidities. Obviously, the long-term goal in those patients is still to attempt to cure the disease, which is mostly achieved with allogeneic stem cell transplant. We are always asking ourselves, “Is that patient a candidate for allogeneic stem cell transplant?” One would consider transplant for a patient as long as he or she is functional and doesn’t have major comorbidities that would prevent them from going to transplant. The margin of benefit of transplant varies based on the age, and that’s a discussion to have with the patient—about whether they want to go to transplant or not.

However, transplant is usually the second step. We consider the other consolidation step, or the subsequent step. On the short term, we need to decide how to treat those patients to get the leukemia into remission. Obviously, the risk of relapse after transplant is much less if patients go into transplant when they are in remission. And even if patients are not proceeding to transplant, going into remission has clinical benefit in terms of improving survival and quality of life.

The treatment choices that we currently have are intensive chemotherapy or what we call the hypomethylating agents—azacitidine and decitabine. In general, azacitidine and decitabine have been used for patients who are not candidates or are not fit for intensive chemotherapy. For patients who are very old, above age 75 or 80; have a poor performance status; or have renal or liver function impairments, they seem to be reasonable alternatives to chemotherapy. In patients above age 70, the outcome may be similar, but the chances of going into remission are less for those agents.

In terms of the disease, there are emerging data that suggest that patients who have very complex karyotype—several chromosomal abnormalities including what we call monosomies, or thep53mutation—may actually do better with hypomethylating agents than intensive chemotherapy. So we use hypomethylating agents in patients who have poor-risk disease, especially those with thep53mutation or those who have poor performance or cannot tolerate intensive chemotherapy.

For intensive chemotherapy, we actually have a couple of options. We have the traditional chemotherapy, which we call 3 + 7. There are different variations and controversy about the optimal dose of the anthracycline that is used in this type of chemotherapy course, but, in the past year, we had the approval of a drug that is liposomal cytarabine and daunorubicin. This was approved for patients with therapy-related AML or MDS progressing to AML, or with AML with MDS-related changes or karyotypes similar to MDS. So that drug is now used for that subset of patients, like the case we are discussing, which is a classical therapy-related AML. In this case, we are considering intensive chemotherapy. That would probably be the first choice. Obviously, clinical trials are also an option for those patients. We always encourage patients to consider clinical trials, because there is still room for improvement in their outcomes.

Transcript edited for clarity.

Case: A 67-Year-Old Man with Therapy-Related AML

  • A 67-year-old man who had received CHOP for diffuse large B-cell lymphoma 3 years prior
  • PMH: hypertension controlled with amlodipine
  • Laboratory results:
    • WBC 15 x 109/L
    • Serum creatinine 1.5 mg/dL
    • Normal LFTs
    • LVEF 50%
  • Diagnosis: Acute Myeloid Leukemia
  • ECOG PS 1
  • The patient received liposomal cytarabine and daunorubicin
  • His course was complicated by febrile neutropenia
  • After induction, <5% marrow blasts, neutrophil count (>1400/&micro;L), platelets 60,000/&micro;L