PS1024 IMPACT OF MINIMAL RESIDUAL DISEASE AND COMPLETE REMISSION (CR)/CR WITH PARTIAL HEMATOLOGIC RECOVERY ON SURVIVAL AFTER GILTERITINIB THERAPY IN PATIENTS WITH FLT3‐MUTATED RELAPSED/REFRACTORY AML

Background: Gilteritinib, a highly selective FLT3 inhibitor, demonstrated strong antileukemic activity at doses ≥80 mg/day in patients with FLT3 ‐mutated ( FLT3 mut+ ) relapsed/refractory (R/R) AML enrolled in the CHRYSALIS phase 1/2 study (NCT02014558). Aims: We analyzed the impact of minimal residual disease (MRD) and achievement of complete remission/complete remission with partial hematologic recovery (CR/CRh) on overall survival (OS) in patients with FLT3 mut+ R/R AML from the CHRYSALIS study. Methods: Minimal residual disease was assessed by next‐generation sequencing (NGS) using an Illumina ® sequencing platform that quantified FLT3 ‐ITD and total FLT3 alleles in FLT3‐ ITD mut+ patients who had bone marrow samples available at baseline and at ≥1 post‐baseline time point. The ITD variant allele frequency (VAF) was the FLT3 ‐ITD to total FLT3 ratio. An ITD VAF ≤10 −4 defined MRD‐negative (MRD−) status. For FLT3 VAF, a capture‐based NGS assay that included all FLT3 exons was used. Treatment response was evaluated according to the CR/CRh rate, where CRh was defined as absolute neutrophil count >0.5 × 10 9 /L and platelet count >50 × 10 9 /L. Results: Of the 108 FLT3 ‐ITD mut+ patients analyzed for MRD, 95 had received ≥80 mg/day gilteritinib, which was shown to induce maximum FLT3 inhibition and antileukemic response. Of the 95 patients, 82 were MRD‐positive (MRD+) and 13 achieved MRD− status at any post‐baseline time point; 49 of 95 patients had a best overall response (BOR) of composite complete remission (CRc; ie, CR plus CR with incomplete hematologic or platelet recovery) and 11 were MRD−. No patient who received <80 mg/day gilteritinib achieved MRD− status. Of the 46 patients who did not achieve CRc, two were MRD−. Patients who had achieved CRc and were MRD− (n = 11) had longer median OS (168.7 weeks) than those who had achieved CRc and were MRD+ (n = 38; 36.1 weeks; P  = .004) ( Figure 1 ). Excluding patients with an OS duration less than the median time to reach MRD− status, MRD− patients (n = 12) had a median OS of 131.4 weeks (95% CI: 35.1, not reached) compared with MRD+ patients (n = 38) who had a median OS of 47.3 weeks. Of the 95 patients who received ≥80 mg/day gilteritinib in the MRD analysis, 24 had a best overall response of CR/CRh. Of the 24 patients with CR/CRh, 10 (41.67%) were MRD−. Of the 71 patients without CR/CRh, three (4.2%) were MRD−. Patients who received 120 mg/day gilteritinib were previously shown to have longer survival than patients in other dose cohorts. Of the 56 patients who received 120 mg/day gilteritinib, 13 achieved a BOR of CR/CRh. Patients who achieved CR/CRh had a median OS of 70.6 weeks and a 52‐week survival probability of 66.7%, whereas those who did not achieve CR/CRh had a median OS of 32.4 weeks and a 52‐week survival probability of 20.2% ( Figure 2 ). Summary/Conclusion: Single‐agent therapy with gilteritinib induced deep molecular responses in heavily pretreated patients with FLT3 ‐ITD mut+ R/R AML. Our results suggest a potential association between MRD negativity and longer survival in these patients; achievement of CR/CRh appears to be associated with a higher rate of MRD negativity and longer OS.