Case Review: IDH2-Mutated Acute Myeloid Leukemia

Hetty E. Carraway, MD: Today, we’re going to talk a little bit about a 48-year-old male who presents with 2 weeks of flu-like symptoms and mild petechiae. He ended up going to an emergency room and was found to have abnormal labs, with an elevated white count of 65,000 with 90% blasts. He had anemia, with a hemoglobin of 8.5 g/dL and a platelet count of 65,000/mL. Initially, he was evaluated because he was having some mild petechiae with these lesions on his skin. Because of the abnormal counts, he was further evaluated and admitted for treatment for his acute leukemia. On physical exam, other than the petechiae, he did not have any abnormalities.

Looking at his laboratory evaluation, of course the emergency room was concerned for an acute leukemia diagnosis. This patient underwent evaluation with a bone marrow biopsy and an aspirate, including molecular annotation. The results of those tests did show that this was consistent with an acute myeloid leukemia, and in the bone marrow aspirate, there were 50% blasts and chromosome abnormalities consistent with trisomy 8. Additionally, after some period of time, molecular annotation was consistent with anIDH2mutation at 140Q. There were other tests that were done in his evaluation, including a chest X-ray, an EKG, and another comprehensive metabolic panel, which was also normal.

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