We evaluated standard-of-care (SOC) treatment with or without midostaurin to prevent relapse following allogeneic hematopoietic stem cell transplant (alloHSCT) in patients with acute myeloid leukemia (AML) harboring internal tandem duplication (ITD) in FLT3. Adults (aged 18–70 years) who received alloHSCT in first complete remission, had achieved hematologic recovery, and were transfusion independent were randomized to receive SOC with or without midostaurin (50 mg twice daily) continuously in twelve 4-week cycles. The primary endpoint was relapse-free survival (RFS) 18 months post-alloHSCT. Sixty patients were randomized (30/arm); 30 completed all 12 cycles (midostaurin + SOC, n = 16; SOC, n = 14). The estimated 18-month RFS (95% CI) was 89% (69–96%) in the midostaurin arm and 76% (54–88%) in the SOC arm (hazard ratio, 0.46 [95% CI, 0.12–1.86]; P = 0.27); estimated relapse rates were 11% and 24%, respectively. Inhibition of FLT3 phosphorylation to <70% of baseline (achieved by 50% of midostaurin-treated patients) was associated with improved RFS. The most common serious adverse events were diarrhea, nausea, and vomiting. Rates of graft-vs-host disease were similar between both arms (midostaurin + SOC, 70%; SOC, 73%). The addition of midostaurin maintenance therapy following alloHSCT may provide clinical benefit in some patients with FLT3-ITD AML. (ClinicalTrials.gov identifier: NCT01883362).

Although total duration of tyrosine kinase inhibitor (TKI) therapy and of molecular response at 4 log reduction or deeper (MR4) correlates with treatment-free remission (TFR) success after TKI discontinuation, the optimal cut-off values of the duration remain unresolved. Thus, 131 patients were enrolled into the Canadian TKI discontinuation study. The molecular relapse-free survival (mRFS) was defined from imatinib discontinuation till molecular recurrence, that is, major molecular response (MMR) loss and/ or MR4 loss. We evaluated mRFS at 12 months after imatinib discontinuation, analyzed it according to the imatinib treatment duration and MR4 duration, and calculated P value, positive (PPV) and negative predictive value (NPV) in the yearly cut-off period of time. The shortest cut-off was sought that met the joint criteria of a P value ≤ 0Á05, PPV ≥ 60% and NPV ≥ 60%. We propose six years as the shortest imatinib duration cutoff with a P value 0Á01, PPV 68% and NPV 62%: The patients treated with imatinib duration ≥ 6 years showed a superior mRFS rate (61Á8%) compared to those with less treatment (36Á0%). Also, 4Á5 years MR4 duration as the shortest cut-off with a P value 0Á003, PPV 63% and NPV 61%: those with MR4 duration ≥ 4Á5 years showed a higher mRFS rate (64Á2%) than those with a shorter MR4 duration (41Á9%).

No abstract