Cladribine Combined with Low-Dose Cytarabine as Frontline Treatment for Unfit Elderly Acute Myeloid Leukemia Patients: Results from a Prospective Multicenter Study of Polish Adult Leukemia Group (PALG)

SIMPLE SUMMARY: Treatment 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. ABSTRACT: 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.