Intermediate-dose cytarabine alone versus combination in consolidation therapy for non-transplant acute myeloid leukemia: a retrospective study.

BACKGROUND: Cytarabine (Ara-C) is a cornerstone of acute myeloid leukaemia (AML) treatment, particularly in consolidation therapy. Although high-dose cytarabine (HDAC) has been widely adopted for consolidation in AML, intermediate-dose cytarabine (IDAC) is increasingly favoured due to its comparable efficacy and improved tolerability. However, the potential benefit of combining another agent with IDAC during consolidation therapy has yet to be adequately validated.

PATIENTS: This retrospective study analyzed 204 newly diagnosed adult AML patients who underwent at least two cycles of consolidation therapy with either IDAC monotherapy (N = 84) or IDAC combined with anthracyclines/homoharringtonine (IDAC-plus, N = 120) after complete remission (CR) or complete remission with incomplete count recovery (CRi).

RESULTS: At a median follow-up of 26.5 months, IDAC-plus significantly improved relapse-free survival (RFS) compared to IDAC monotherapy (HR 0.62, p = 0.019). Although overall survival (OS) was not significantly different, the IDAC-plus group showed a survival advantage (HR, 0.68; p = 0.11). Subgroup analysis identified younger patients (HR = 0.43, p = 0.01), male patients (HR = 0.51, p = 0.03), patients with better performance status (HR = 0.52, p = 0.01), lactate dehydrogenase (LDH) >2 × upper limit of normal (ULN) (HR 0.51, p = 0.01), intermediate-risk disease (HR= 0.51 p = 0.01), measurable residual disease (MRD) positivity at CR/CRi (HR = 0.48, p = 0.03) and patients without hyperleukocytosis (HR = 0.64, p = 0.04), can have a more pronounced benefit from IDAC-plus consolidation chemotherapy. IDAC-plus group had more neutropenia (grade ≥3) (p = 0.032), febrile neutropenia (p = 0.039) and documented infection (p = 0.028), but non-relapse mortality (NRM) was similar between the two groups (p = 0.985).

CONCLUSION: The findings suggest that IDAC-based combination consolidation chemotherapy reduces the risk of relapse in non-transplant AML compared to IDAC alone, particularly in patients with intermediate-risk disease or MRD positivity at the time of achieving CR/CRi, underscoring the need for intensified regimens in these populations.