Evaluation of cytarabine consolidation dosing in older adult patients with Acute Myeloid Leukemia

Abstract

Abstract Introduction: Post remission therapy in patients (pts) with acute myeloid leukemia (AML) who are intensive induction candidates consists of cytarabine based consolidation to prevent disease recurrence. For pts ≥ 60 years (yrs) who received intensive induction, current recommendations caution use of high dose cytarabine due to increased risk of cerebellar toxicity. There is minimal real-world data on cytarabine consolidation dosing strategies in pts ≥ 60 yrs. The purpose of this study was to assess the safety and efficacy of high dose cytarabine (HiDAC) and intermediate dose cytarabine (IDAC) in this pt population. Methods: This was a single center retrospective study conducted at The Ohio State University using the Bloomfield Center Database. Pts were included if ≥60 yrs, diagnosed with AML, and received at least one cycle of cytarabine consolidation after induction therapy between March 1, 2013 and December 31, 2024. IDAC and HiDAC were defined as a cumulative cytarabine dose of ≤ 9000 mg/m2 and >9000 mg/m2 for the first cycle, respectively. Descriptive statistics were used to summarize demographic information, toxicity events, and cytarabine dose adjustments/delays. Overall survival (OS) and disease-free survival (DFS) estimates were calculated using the Kaplan-Meier method. HiDAC and IDAC were compared using the log-rank test. Results: We analyzed 113 pts who received at least one cycle of cytarabine consolidation. Median age was 66 yrs (range 60-75); the majority of pts had an ECOG of 1 (65%), baseline creatinine clearance ≥ 60 ml/hr (93%), and received cytarabine consolidation treatment without targeted therapy (79%). In this group, 68 pts received IDAC and 45 received HiDAC. The most common dosing regimen in the IDAC group was 1000 mg/m2 every 24 hours days 1-5 (82%) and 2000 mg/m2 every 12 hours days 1, 3, and 5 (60%) in the HiDAC group. The median number of total cycles in both groups was 2 (range 1-4). Following the first cycle of consolidation, there were 28 (35%) dose delays/adjustments in the IDAC group compared to 36 (69%) in the HiDAC group. The most common reason for delays/adjustments were non-hematologic (n=16, 57%) in pts who received IDAC versus hematologic (n=14, 39%) for those who received HiDAC. There were two pts who permanently discontinued chemotherapy due to toxicity in the IDAC group and one in the HiDAC group. Reasons for discontinuation included symptomatic bradycardia, persistent thrombocytopenia, and infection. For toxicity, there were 49 events identified in all pts who received IDAC and 36 in those who received HiDAC that were related to treatment. The median time to toxicity was 13 days from day one of the most recent consolidation cycle (range 2- 83 days). The most common toxicity events that occurred in the IDAC and HiDAC groups were febrile neutropenia, 34 (69%) and 26 (72%), respectively, followed by bleeding events, 6 (12%) and 5 (14%), respectively. Other toxicities included gastrointestinal toxicity (5%), failure to thrive events (5%), and cerebellar toxicity (2%) for the total cohort. Level of care included hospitalizations (89%), outpatient physician visits (6%), and emergency room visits (5%). The median time to count recovery in all cycles was 24 days (range 15-60) in pts who received IDAC and 25 days (range 15-128) in pts who received HiDAC. Rate of allogeneic stem transplant was 50% in the IDAC group and 64% in the HiDAC group (p=0.18). The median DFS was 27 months in the IDAC group and 56 months in the HiDAC group (p=0.31), and OS was 42 months in pts who received IDAC and 69 months in pts who received HiDAC (p=0.30). Conclusion: Overall, there was no statistically significant difference in efficacy between pts who received IDAC and HiDAC; however, there were numerical differences in survival outcomes. Surprisingly, there were more toxicity events in pts who received IDAC, but this may be due to selection bias as these pts were initially deemed unfit for higher intensity consolidation treatment. Although there were fewer toxicities in the HIDAC group, there were more dose adjustments and delays that affected treatment. This analysis was limited by sample size; therefore additional real-world analysis is needed to further explore dosing strategies in older pts with AML. Future results from this study will include efficacy outcomes related to mutations and cytogenetic abnormalities.