Better survival with fludarabine and timed sequential busulfan regimen in older patients with AML/MDS

7046 Background: We previously reported 6% 100 day NRM with a MA fludarabine (Flu) and busulfan (Bu) in older patients with a median age of 60 years. MA dose of Bu in this timed sequential (TS) regimen was administered over a longer period of time. To assess its impact on survival, we compared the outcomes of older patients treated with the TS Bu (TS cohort) or the RIC Flu/Bu regimen, which is used as standard (ST) for older patients at our center (ST cohort). Methods: Patients in the TS cohort received IV Bu 80 mg/m2/d on day -13 and -12 and Flu 40 mg/m2/d followed by IV Bu on day -6 to -3, dose adjusted to achieve a total Bu course AUC of 20,000 μmol-min based on PK studies. Patients in the ST cohort received Flu 40 mg/m2day followed by IV Bu daily for 4 days (day -6 to -3) dosed to achieve AUC of 16,000 μmol-min. Patients with AML or MDS were eligible for the study if they had adequate organ function, had matched related or unrelated donor and were treated between Jan 2012 and Sept 2016. Results: 162 patients, 50 with MDS and 112 with AML, were included in this study. Patient characteristics including age, sex, disease status, cytogenetic risk group, donor type, graft source CMV status and comorbidity were well balanced and without any significant difference in the two cohorts. Median age was 66 and 65 years in ST and TS cohorts, respectively. Overall survival (OS) and progression free survival (PFS) were significantly better in the TS cohort (see Table). This was due to a reduction in the disease progression without any increase in the non-relapse mortality (NRM). After adjusting for other covariates, the multivariate analysis for PFS confirmed longer PFS with TS Bu regimen (HR: 0.36; P=0.003). The benefit was mainly seen in patients with a comorbidity score ≤ 3. Conclusions: The myeloablative timed sequential Bu regimen improves survival and appears promising in older patients with AML/MDS. Clinical trial information: NCT01572662. [Table: see text]