Advantages of Oral Enasidenib in IDH2-Mutated AML

Hetty E. Carraway, MD:Traditionally, the therapy that we give to patients is chemotherapy, very intensive. It requires that they’re often in the hospital, at least with induction chemotherapy, for 30 days. For those patients that get reinduction chemotherapy, then they’re in the hospital for at least another 30 days. Some of this can be done as an outpatient, depending on where the patient was treated. In the context of using enasidenib 100 mg by mouth daily, this is an agent that you can give to a patient, and they can take it at home, and you can follow them in the outpatient setting with just checking their counts regularly and seeing them. In the package insert, it recommends that physicians follow patients at least every 2 weeks with complete blood counts. For some patients, you may want to do things a little bit more frequently, depending on whether or not they’re having symptoms and what their lab values may look like.

I think it really is up to the physician to direct the therapy, according to the patient that’s taking this agent and how they’re tolerating it. It can be pretty stark in contrast when you see a patient that’s able to take a medication like this at home, in comparison to what we normally do—we keep them in the hospital and require that they be in the hospital for prolonged periods of time. They lose quite a bit of independence. They lose a lot in terms of their physical performance, and there’s a lot of emotional depression that comes with feeling pretty restricted in the hospital and not surrounded by your loved ones. So, I think an agent like this has been meaningful. The downside is that it isn’t for every patient with AML. It really only pertains to about 10% of patients that have AML. So, to that end, I think we’re striving to make sure that we work to find therapies like this for more patients, and hopefully we’ll be able to do that in years to come.

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