Wolschke, Christine

PURPOSE Allogeneic hematopoietic cell transplantation (HCT) improves outcomes for patients with AML harboring an internal tandem duplication mutation of FLT3 ( FLT3-ITD) AML. These patients are routinely treated with a FLT3 inhibitor after HCT, but there is limited evidence to support this. Accordingly, we conducted a randomized trial of post-HCT maintenance with the FLT3 inhibitor gilteritinib (ClinicalTrials.gov identifier: NCT02997202 ) to determine if all such patients benefit or if detection of measurable residual disease (MRD) could identify those who might benefit. METHODS Adults with FLT3-ITD AML in first remission underwent HCT and were randomly assigned to placebo or 120 mg once daily gilteritinib for 24 months after HCT. The primary end point was relapse-free survival (RFS). Secondary end points included overall survival (OS) and the effect of MRD pre- and post-HCT on RFS and OS. RESULTS Three hundred fifty-six participants were randomly assigned post-HCT to receive gilteritinib or placebo. Although RFS was higher in the gilteritinib arm, the difference was not statistically significant (hazard ratio [HR], 0.679 [95% CI, 0.459 to 1.005]; two-sided P = .0518). However, 50.5% of participants had MRD detectable pre- or post-HCT, and, in a prespecified subgroup analysis, gilteritinib was beneficial in this population (HR, 0.515 [95% CI, 0.316 to 0.838]; P = .0065). Those without detectable MRD showed no benefit (HR, 1.213 [95% CI, 0.616 to 2.387]; P = .575). CONCLUSION Although the overall improvement in RFS was not statistically significant, RFS was higher for participants with detectable FLT3-ITD MRD pre- or post-HCT who received gilteritinib treatment. To our knowledge, these data are among the first to support the effectiveness of MRD-based post-HCT therapy.

Abstract Background: Myelofibrosis (MF) is a bone marrow disorder characterized by anemia, splenomegaly and constitutional symptoms. There has been substantial work documenting quality of life (QoL) in patients with MF, however, very little data about patients following allogeneic stem cell transplant (alloSCT) for MF. Many patients decline alloSCT due to concerns secondary to QoL. Methods: Medical facts and patient reported outcomes (PRO) measures were collected within a month prior to transplant, at day 30, 100 and 1 year post alloSCT. PRO measures include Brief Fatigue Inventory, Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT), global assessment of change and the Myeloproliferative Neoplasms Symptom Assessment Form (MPN-SAF). The group was measured as a whole, and the patients in the upper quartile of MPN-TSS (the aggregate score of the 10 core items of the MPN-SAF) were also considered. Results: Fifty patients were enrolled on this study, 47 who proceeded with transplant. The median age of the patients was 63, ranging from 35-74. The majority of the patients were male (29, 66%), and Caucasian (43 (96%)). Most patients had primary MF (26, 59%), 9 patients had post-PV MF, and 9 patients had post-ET MF. Twenty patients had DIPSS Intermediate 2 risk disease, and 16 had DIPSS high risk disease. Twenty-six (51%) had a matched unrelated donor, 12 (30%) had a matched related donor and 5 (12%) had a mismatched unrelated donor. The majority of the patients had RIC regimens (35, 88%). At baseline the mean MPN-TSS was 27.7 (out of possible 100), and at day 30, day 100 and 1 year it was 24.6, 32.0, and 25.0, which reflected no significant change between the time points. Interestingly, all the MPN specific symptoms (including fevers, night sweats, pruritis, abdominal pain) had a significant improvement at least one time point following alloSCT. Patients in the highest quartile based on baseline TSS score (12 patients with scores at baseline greater than or equal to 37), had significant improvement in TSS score at day 100, headache at day 30, insomnia at day 100, night sweats at day 100, itching at day 100 and overall QOL at day 100. With regards to the FACT BMT, as would be expected, there was a significant decline in the FACT BMT total score, as well as trial outcome index (TOI) at day 30, but a return to close to baseline by one year. In the global assessment of change, on day 30, 11 (27.5%) of patients reported feeling a little/moderately/very much better overall quality of life since their transplant and 27 (67.5%) felt a little/moderately/very much worse quality of life. At day 100, 11 (31.4%) reported better quality of life and 20 (57%) reported worsening since transplant. By one year, 17 (60.7%) reported feeling better and 7 (25%) reported worsening. These findings did not appear to have a correlation with presence or absence of graft versus host disease. We were unable to assess the impact of conditioning as the majority of the patients had RIC conditioning. Discussion/ Conclusions: Our study evaluated the quality of life in patients with myelofibrosis who have undergone bone marrow transplantation. We have shown that there is very little change in symptom burden over the first year following transplant in general; however, significant improvement was observed in MF specific symptoms, and in patients who had a high symptom burden at baseline. By one year 61% felt that their QoL was better than it was prior to transplant. Our findings suggest that many of the patients do not experience a significant decline in QoL at 1 year after alloSCT, and actually report that their QoL improves. Further investigation is required to validate these findings. Figure. Figure. Disclosures Palmer: Novartis: Research Funding. Dueck:Phytogine: Employment; Pfizer: Honoraria; Bayer: Employment. Mesa:Novartis: Consultancy; NS Pharma: Research Funding; Incyte Corporation: Research Funding; UT Health San Antonio - Mays Cancer Center: Employment; Pfizer: Research Funding; CTI Biopharma: Research Funding; Celgene: Research Funding; Promedior: Research Funding; Gilead: Research Funding; Genentech: Research Funding.