Efficacy and safety of cladribine, low-dose cytarabine and venetoclax in newly diagnosed and relapsed/refractory acute myeloid leukemia: results of a single center study

Ann Hematol. 2025 May;104(5):2745-2753. doi: 10.1007/s00277-025-06389-9. Epub 2025 May 20.

Abstract

The aim of this study was to assess the safety, response, and survival outcomes of cladribine (CLAD) + low-dose cytarabine (LDAC) + venetoclax (CAV) in patients with relapsed/refractory (R/R) and newly diagnosed acute myeloid leukemia (AML). This single-center, retrospective, non-randomized study included 46 adult patients with 29 R/R AML and 17 newly diagnosed AML who were unfit for intensive chemotherapy. All patients received the CAV regimen at our center. In the R/R group (median age 55 years, range 21-77), complete response (CR) was achieved in 44.8%, CR with incomplete blood count recovery (CRi) in 24.1%, composite complete remission (CRc, CR + CRi) and measurable residual disease (MRD) negativity in 51.7%. The median follow-up was 10.9 months, with median overall survival (OS) of 16.4 months (95% CI, 10.9-21.8). Leukopenia (62.1%) was the most common hematologic toxicity, and infection (44.8%) was the most common non-hematologic toxicity. The 30-day mortality rate was 0%, and one patient died within 60 days. In the newly diagnosed group, CR was 76.5%, CRi 17.6%, CRc 94.1%, and MRD negativity 82.3% after one induction cycle. The median OS was 15.5 months (95% CI, 11.1-19.9). Common grade 3/4 hematologic toxicities were leukopenia (76.5%), with infection (52.9%) as the most common non-hematologic toxicity. The CAV regimen demonstrated a high CRc rate and MRD negativity in R/R AML with manageable toxicity. In newly diagnosed acute myeloid leukaemia, this regimen has also demonstrated favourable efficacy, as previously reported, with tolerable haematological toxicity.

Keywords: Acute myeloid leukemia; Cladribine; Efficacy; Venetoclax.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols* / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic / administration & dosage
  • Bridged Bicyclo Compounds, Heterocyclic / adverse effects
  • Cladribine* / administration & dosage
  • Cladribine* / adverse effects
  • Cytarabine* / administration & dosage
  • Cytarabine* / adverse effects
  • Female
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / mortality
  • Male
  • Middle Aged
  • Recurrence
  • Retrospective Studies
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / adverse effects
  • Survival Rate
  • Treatment Outcome
  • Young Adult

Substances

  • Cytarabine
  • venetoclax
  • Sulfonamides
  • Cladribine
  • Bridged Bicyclo Compounds, Heterocyclic