Real-world outcomes of cytarabine consolidation in older patients with acute myeloid leukemia.

Abstract

e18535 Background: Acute myeloid leukemia (AML) predominantly affects elderly patients. Standard of care treatment includes induction chemotherapy, followed by consolidation with 4 cycles of high dose cytarabine (HiDAC) at 3gm/m2 with or without allogeneic stem cell transplantation (alloSCT). HiDAC dose was established based on CALGB 8525, which showed an improved leukemia-free survival compared to lower doses cytarabine. Older patients did not have the same benefit due to increased mortality and neurotoxicity. There has not been a formal study of ideal dosing of consolidation for older patients. Our institution has utilized an approach for reducing the dose of HiDAC for patients aged ≥60. Methods: We conducted a retrospective analysis of AML patients aged ≥60 treated with Ara-C consolidation at UPMC between January 1, 2004 and September 19, 2022. We described the dosing characteristics and incidence of neurotoxicity of patients who received at least one full cycle of consolidation Ara-C (6 doses total given on days 1,3,5). We evaluated the association between Ara-C dose, number of completed cycles, overall survival (OS) and relapse free survival (RFS). Results: 156 patients ≥60 years were included (median, 66.1 years; range, 59.6-78.3). Neurotoxicity was observed in 3 patients; after the 1 st cycle at 2gm/m2, 1 st cycle at 1gm/m2 and 2 nd cycle at 2gm/m2 respectively. Median Ara-C dose per cycle was 1.5 gm/m2 (range, 1.0-3.0). 41% of patients received a median dose ≥2gm/m2 per cycle. Over half of patients (58%) completed 4 cycles; 43% of these patients received a median dose ≥2gm/m2 per cycle. Among all patients, the most common reasons for discontinuation were progression (24 patients, 17%) and alloSCT (8 patients, 5%). Median OS for the entire cohort was 1.8 years. 26 patients (16.8%) received alloSCT. Number of cycles completed correlated with improved OS (p<0.001). Among patients who completed 4 cycles, median OS was 4.8 years (95% CI 1.8-NR) in those who received Ara-C at a dose of ≥2gm/m2 versus 2.7 years (95% CI 1.9, 5.3) in those who received Ara-C at <2gm/m2. The hazard ratio (HR) for OS with ≥2gm/m2 at 4 cycles was 0.5 (95% CI 0.3-0.9; p=0.02). In the group of patients who received 4 cycles median RFS was 1.71 years (95% CI 1.29-5.18) at ≥2gm/m2 versus 1.56 years (95% CI 1.28-2.37 ) at <2gm/m2. HR was 0.7 (95% CI 0.4-1.1; p=0.16). Conclusions: Cytarabine consolidation in patients ≥60 years with AML is safe and feasible. Neurotoxicity was rare, especially at reduced dose. We observed improved OS after completing the full 4-cycle Ara-C consolidation regimen. Similarly, there were improved outcomes with median Ara-C dose ≥2gm/m2 per cycle for those who received 4 cycles. RFS was not statistically different in our limited sample which might be suggestive of a similar leukemia-free survival at both higher and lower dose of Ara-C. We plan to further analyze the characteristics of patients who derived most benefit from higher dose of Ara-C.