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Background: Leukemia recurrence remains a continuing cause of treatment failure post-allogeneic hematopoietic cell transplantation (allo-HSCT) in FLT3-mutated AML patients (pts). Maintenance therapy with FLT3 inhibitors is a promising strategy to reduce the risk of relapse risk. Currently, no FLT3 inhibitors have been approved. Crenolanib is a highly potent and selective type-1 FLT3 inhibitor that has activity both as a single agent and in combination with chemotherapy in pts with FLT3-ITD and FLT3-TKD mutations. Here we report the long-term follow-up data of a phase II trial (NCT02400255) evaluating the safety and potential efficacy of crenolanib maintenance in FLT3+ AML pts following allo-HSCT. Materials and Methods: Pts aged 18+ with FLT3+ AML (FLT3-ITD and FLT3-TKD) following allo-HSCT were enrolled. Pts received crenolanib 42-90 days post-HSCT. Crenolanib doses ranged from 60 mg BID to 100 mg TID. Intra-patient dose escalation was permitted based on crenolanib tolerability. The primary objective was to evaluate the safety and tolerability of crenolanib in the post-HSCT setting. The secondary objectives were overall survival (OS) and relapse-free survival (RFS). For this updated analysis, all patients were followed for five years, and RFS and OS are presented for the entire study population. Patient Demographics: 30 FLT3+ AML pts (range 24-74 years, median 53) were enrolled between September 23, 2015, and March 10, 2020. Pts received crenolanib maintenance for up to two years post-HSCT. 22 pts underwent HSCT in CR1, 5 in CR2, 1 in CR3 and two patients had residual disease at the time of transplantation. 20 patients had prior exposure to at least one TKI, with 16 receiving sorafenib. Twenty-five pts had detrimental co-occurring mutations, including 7 with the DNMT3A/NPM1/FLT3 triple mutation, 7 with RUNX1 mutations, and 12 with WT1, IDH1/2, or TET2 mutations. 3 pts had poor prognostic gene fusions including one each with DEK-NUP214, MLL-MLLT3, and ETV6 rearrangement. Results: Crenolanib showed a favorable safety profile, consistent with the known and anticipated risks of crenolanib. The most frequently reported treatment-emergent adverse events (TEAEs) were nausea (57%), vomiting (47%), and diarrhea (47%). A majority of these events were grade 1 or 2 in severity and were generally well managed with standard anti-emetics or anti-diarrheals. Nausea decreased with each new dose-increase cycle. No significant myelosuppression was observed. Five cases of GVHD were reported, with four of these patients having a history of acute GVHD at the time of enrollment. We are reporting the RFS and OS on all 30 pts enrolled (including the 6 pts transplanted in CR2/CR3 and 2 pts with residual disease). The follow-up is mature with a median follow-up time of 58.3 months. For these 30 pts, the 5-year RFS was 69.7% (95% CI, 54.9-88.4%) and the 5-year OS was 69% (95% CI, 54.0-88.2%). Of the nine relapses, five were observed within 28 days of initiation of crenolanib maintenance (7-28 days). This trial did not require bone-marrow assessment before initiation of crenolanib maintenance and these very early relapses suggest the presence of active disease at the time of study entry. Among the 20 pts who received at least 28 days of crenolanib maintenance, only three pts relapsed during crenolanib maintenance. Of the 19 FLT3-ITD AML pts transplanted in CR1, three relapses were seen. Only one patient relapsed post-completion of maintenance (11 months). The 5-year RFS was 78.9% (95% CI, 62.6-99.6%), and the 5-year OS was 84.2% (95% CI, 69.3-100.0%). CONCLUSION: With a median follow-up of 5 years, crenolanib maintenance in the post-HSCT setting was well tolerated with no increase in myelosuppression or GVHD. Although this trial is too small to make a statement about efficacy, only three relapses were seen in the 20 pts who received at least 28 days of crenolanib maintenance. The RFS of 78.9% and OS of 84.2% in pts transplanted in CR1 with FLT3-ITD is encouraging. Trials are being planned to formally assess the potential benefit of crenolanib in preventing relapse in the post-transplant setting.