BACKGROUND
An improved understanding of the pathogenesis of leukemia has led to the development of targeted therapies, such as FMS-like tyrosine kinase 3 (FLT3) and Isocitrate Dehydrogenase (IDH) inhibitors. These treatments have proven efficacy in Acute Myeloid Leukemia (AML), but data in Acute Lymphoblastic Leukemia (ALL) are lacking.
CASE DISCUSSIONS
We found 14 ALL patients in our database with FLT3, IDH1, or IDH2 mutations (Table1). All T- cell ALL patients were diagnosed with Early T-cell precursor ALL (ETP-ALL). FLT3 mutations were found in 6 patients with B-ALL and 2 with ETP-ALL, 2 patients with B-ALL were IDH1 mutated, and 4 patients with ETP-ALL were IDH2 mutated. Three patients eventually received FLT3 or IDH inhibitors (Figure1).
Patient 1 was diagnosed with IDH2 mutated ETP-ALL at the age of 65. He achieved complete remission (CR) with measurable residual disease (MRD) positivity after induction chemotherapy. However, consolidation chemotherapy was stopped given life-threatening adverse events. He received enasidenib as maintenance therapy and remains in remission 20 months after his diagnosis.
Patient 2 was diagnosed with IDH2 mutated ETP-ALL at the age of 60 and received enasidenib to treat her relapsed leukemia. She achieved a CR with MRD positivity and relapsed 27 months later.
Patient 3 was diagnosed with FLT3-tyrosine kinase domain mutated ETP-ALL at the age of 34 and was refractory to chemotherapy upon relapse. He then received gilteritinib and venetoclax for 4 weeks, after which he continued gilteritinib alone due to a subdural hemorrhage. He achieved a CR without MRD and relapsed after 8 months.
CONCLUSION
Despite the higher prevalence of IDH and FLT3 mutations in AML, they are also seen in ALL. Although further data are required to confirm efficacy, these cases suggest that FLT3 and IDH inhibitors could represent a viable therapeutic option for these patients.
