Propensity-score Matched Comparison of Salvage Chemotherapy Regimens in Relapsed/Refractory Acute Myeloid Leukemia

Clin Lymphoma Myeloma Leuk. 2021 Jun;21(6):393-400.e1. doi: 10.1016/j.clml.2021.01.011. Epub 2021 Jan 19.

Abstract

Background: Relapsed/refractory acute myeloid leukemia (AML) confers a poor prognosis, and there is no single standard of care first-line salvage regimen. FLAG (fludarabine, cytarabine, and granulocyte colony-stimulating factor) is a common salvage regimen with a favorable toxicity and efficacy profile in poor-risk AML.

Materials and methods: We conducted a single-center, retrospective analysis of first relapse/primary refractory patients with AML that received salvage chemotherapy from January 2009 to July 2019. We propensity-score matched patients 1:1 (based on age at diagnosis, cytogenetic risk group, Charlson comorbidity index, de novo vs. secondary AML, and whether or not they received an allogeneic stem cell transplant in first complete remission) into 2 groups, FLAG (Group 1) or non-FLAG (Group 2) as first-line salvage regimen, with 66 patients in each group. The primary endpoint was overall response rate (complete response and complete response with incomplete hematologic recovery).

Results: The median patient age was 59 years (range, 19-80 years). Patients treated with FLAG had a higher overall response rate (complete response/complete response with incomplete hematologic recovery) (71.2% vs. 50.0%; odds ratio, 2.47; 95% confidence interval [CI], 1.21-5.08; P = .013), longer event-free survival (8.9 vs. 2.1 months; hazard ratio [HR], 0.58; 95% CI, 0.39-0.86; P = .005), and longer overall survival (14.2 vs. 5.9 months; HR, 0.62; 95% CI, 0.41-0.93; P = .019). Patients who received FLAG had a shorter median duration of neutropenia (22 vs. 34 days; HR, 0.43; 95% CI, 0.29-0.64; P < .001).

Conclusion: This analysis supports the FLAG regimen as an effective and well-tolerated salvage therapy for patients with relapsed/refractory AML.

Keywords: AML; Cytarabine; FLAG; Fludarabine; Re-induction.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor
  • Disease Management
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Leukemia, Myeloid, Acute / diagnosis
  • Leukemia, Myeloid, Acute / drug therapy*
  • Leukemia, Myeloid, Acute / etiology
  • Leukemia, Myeloid, Acute / mortality*
  • Male
  • Middle Aged
  • Prognosis
  • Propensity Score
  • Recurrence
  • Retreatment
  • Retrospective Studies
  • Salvage Therapy
  • Treatment Outcome

Substances

  • Biomarkers, Tumor