Targeted Therapies and the Treatment of AML

Hetty E. Carraway, MD:Let’s talk a little bit about whether or not it’s appropriate for this patient to actually go to transplant, now that he’s achieved a complete remission. This is CR1, his first complete remission, and the appropriate thing to do for this young patient, 48 years old, if he’s otherwise healthy—has good performance status, normal lungs, normal kidney, normal liver function tests—is to proceed to a bone marrow transplant; the intent there being for curative intent. Transplant really is our mainstay of cure. In a patient that has primary refractory disease, transplant is going to be the best therapy for them, and it’s fortunate that enasidenib could get him to that place.

Acute myeloid leukemia has really changed in the last year, and the therapies for AML have really changed in the last year. It’s been pretty exciting to see these novel therapies emerge, therapies that we would not have ever thought about. The experience as a clinician in using oral agents as targeted therapy for patients is really an unusual thing. When you see patients have less side effects and they are able to respond to therapies like this, and even potentially get to transplant with an oral medication while at home, that is such a foreign concept. The juxtaposition of that type of therapy versus the intensive chemotherapy that we give them, really is amazing to witness at this time. I don’t take that for granted, just given the number of patients that we’ve tried to cure over the years. As a result of that, I feel like we’re taking steps closer and closer to getting better control over AML.

I do believe that next-generation sequencing has helped us to design better drugs, potentially targeted drugs. Always, when we have advances like this, there are more questions than answers. As you know, as we talked about with this particular drug, only a small proportion of patients will benefit from this. But, hopefully, with incremental changes and additions, we’ll get to a bigger piece of the pie, as we compile these small wins altogether.

Transcript edited for clarity.

A 48-Year-Old Male With Chemo-Refractory AML

• A healthy 48-year-old man visited his PCP for flu-like symptoms lasting more than 2 weeks. He is married, with 3 school-age children and is an avid golf and tennis player.
• PE: mild petechiae on lower extremities; otherwise unremarkable
• Labs:
  • WBC, 65,000 (90% blasts)
  • Hb, 8.5 g/dL
  • Platelets 65,000/mL
  • ANC 2.5/mm³
  • LDH, 392 U/L
• Bone marrow biopsy:
  • 50% blasts
  • Cytogenetics; +8
  • NGS;IDH2(R140Q) mutation
• Liver and cardiac workup, WNL
• The patient received 7+3 induction chemotherapy and subsequently reinduction without achieving a remission
• The patient was then started on enasidenib
• He achieved stable disease after 2 cycles of therapy
• After 3 cycles, peripheral blasts, 15%; ANC, 1.1/mm³
  • 2 weeks later, patient reports dyspnea on exertion and mild swelling
  • PE notable for rales bilaterally
  • Chest X-ray shows bilateral diffuse pulmonary infiltrates
  • Additionally, indirect bilirubin, 1.9 mg/dl
  • Patient was started on dexamethasone 10 mg bid and antibiotics; pulmonary symptoms resolved in 1 week
• Bone marrow biopsy after 6 cycles shows morphologic CR, 2% blasts by FC; NGS shows persistence of mutantIDH2
• Patient referred for allogeneic transplant