Abstract
Simple SummaryTreatment of acute myeloid leukemia (AML) in elderly patients unfit for intensive chemotherapy (IC) is a challenge in clinical practice. Here we prospectively evaluated a novel low-intensity regimen consisting of low-dose cytarabine combined with cladribine (LD-AC+cladribine) for remission induction followed by LD-AC alone in the maintenance phase as the frontline treatment for elderly AML patients ineligible for IC. We included a cohort of 117 elderly patients in poor performance status or with significant comorbidities. High-risk or intermediate-risk cytogenetics were observed in almost 90% of patients. Treatment with LD-AC+cladribine led to the objective response rate of 54% and the median overall survival of 17.3 months in the responders group. The toxicity profile was predictable and infectious complications were the most common non-hematological adverse events. In conclusion, we found LD-AC+cladribine as a beneficial therapeutic option with an acceptable safety profile in the difficult-to-treat population of elderly AML patient ineligible for IC.Acute myeloid leukemia (AML) in older unfit patients is a therapeutic challenge for clinical hematologists. We evaluated the efficacy and safety of a novel low-intensity regimen consisting of low-dose cytarabine and cladribine (LD-AC+cladribine) in first-line treatment of elderly (≥60 years) AML patients not eligible for intensive chemotherapy (IC) who had either the Eastern Cooperative Oncology Group performance status (ECOG PS) ≥2 or the hematopoietic cell transplantation comorbidity index (HCT-CI) score ≥3. The induction phase included two cycles of LD-AC+cladribine. Patients who achieved at least partial remission (PR) received maintenance treatment with LD-AC alone. Overall, 117 patients with a median age of 70 years were enrolled. Adverse cytogenetics, ECOG PS ≥2 and HCT-CI score ≥3 was observed in 43.5%, 60%, and 58% of patients, respectively. The response rate (≥PR) was 54% (complete remission [CR], 32%; CR with incomplete hematologic recovery [CRi], 5%). A median overall survival (OS) was 21 and 8.8 months in CR/CRi and PR group, respectively. Advanced age (≥75 years) and adverse cytogenetics had a negative impact on OS. The 56-day mortality rate was 20.5%. In conclusion, LD-AC+cladribine is a beneficial therapeutic option with a predictable safety profile in elderly AML patients not eligible for IC.
Highlights
Acute myeloid leukemia (AML) most commonly affects older adults with a median age of 68 years at diagnosis [1]
The AML landscape changes with the increasing age of patients with high-risk cytogenetics, overexpression of genes contributing to treatment resistance, secondary AML after antecedent hematological disorders, and therapyrelated AML, more frequently observed in older patients [2,3,4,5,6,7]
To improve outcomes in this difficult-to-treat population of AML patients, we investigated a novel non-intensive therapeutic approach consisting of low-dose cytarabine (LD-AC) in combination with cladribine (LD-AC+cladribine) for remission induction followed by LD-AC monotherapy in maintenance phase
Summary
Acute myeloid leukemia (AML) most commonly affects older adults with a median age of 68 years at diagnosis [1]. Several predictive models are helpful in the decision-making process [13,14,15,16,17], the most commonly used being the hematopoietic cell transplantation comorbidity index (HCT-CI). In this model, a score of 2 or more defines a subgroup of older adults characterized by lower remission rate, increased early mortality, and decreased survival when IC is applied [13,14]
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