FLAG-Ida-Venetoclax vs CLIA-venetoclax for relapsed and refractory AML during a fludarabine shortage: A single center experience

Objective Intensive chemotherapy combinations with venetoclax are being used more frequently for acute myeloid leukemia (AML). In May 2022, a critical shortage of fludarabine prompted cladribine substitution at several institutions in the United States. FLAG-Ida-Ven and CLIA-Ven are similar IC regimens using different purine analogues, potentially with different efficacy and toxicity. To describe the patient population, outcomes, and toxicities of patients receiving FLAG-Ida-Ven and CLIA-Ven. Data Sources A retrospective analysis of patients over 18 years with AML who received FLAG-Ida-Ven or CLIA-Ven for relapsed/refractory AML (R/R AML) at the City of Hope between December 2020 and January 2023. Data Summary There were 31 patients who received FLAG-Ida-Ven; 8 patients received CLIA-Ven. Patients were identified using ICD-10 code for AML and documented administration of medications. Most patients included were male with de novo AML with ELN adverse risk AML. Median age was 53 years (20–78) for FLAG-Ida-Ven and 47.5 years (23–69) for CLIA-Ven. Prior exposure to venetoclax based therapy was common (61.3% vs 50%). The ORR (overall response rate) in FLAG-Ida-Ven and CLIA-Ven was 46.7% and 75%, of which 86% vs 83% were MRD negative, respectively. There were 42% (n = 13) and 50% (n = 4) of patients who were able to proceed to allogeneic stem cell transplant in the FLAG-Ida-Ven and CLIA-Ven with median time to transplant being 89 vs 132 days respectively. Regarding safety, CLIA-Ven had a higher incidence of grade 3 or 4 non-hematologic adverse events, 6% vs 50% respectively. Survival from therapy initiation at 6 months was 48.4% vs 75%. Conclusion Consistent with the literature, it appears that the activity between FLAG-Ida-Ven and CLIA-Ven are comparable, however FLAG-Ida-Ven may have a more tolerable safety profile.