Single-Center Retrospective Clinical Evaluation of Venetoclax Combined with HMAs and Half-Dose CAG for Unfit or Refractory/Relapsed AML

Abstract

Purpose

The prognosis of patients with unfit or relapsed/refractory (R/R) AML remains poor. Venetoclax (VEN) has been shown to exhibit anti-leukemia stem cell activity; however, few studies have been published on the efficacy and safety of VEN combined with both hypomethylating agents (HMAs) and low-dose chemotherapy for patients with unfit or R/R AML.

Methods

This study retrospectively analyzed the clinical characteristics, treatment details, safety profile and clinical outcomes of patients with unfit or R/R AML treated with VEN+ HMAs+ half-dose CAG (LDAC, aclarubicin and granulocyte colony-stimulating factor).

Results

A total of 24 AML patients were involved in the study, of whom 13 (54.2%) were in the unfit group, and 11 (45.8%) were in the R/R group. FLT3 and IDH (8/24, 33.3%) were the most common gene aberrations. Patients in the R/R group were found to be more likely to carry KIT (5/11, 45.5%) compared with the unfit group (0/13, 0%) (P = 0.006). The ORR observed during the study was 83.3% (20/24; 14 CR, 2CRi, 4PR). In the unfit group, 11/13 (84.6%) patients achieved cCR (10 CR and 1 CRi); while 5/11 (45.5%) R/R patients achieved response (4 CR and 1 CRi). CR was observed in all AML patients with TP53 (5/5), GATA2 (3/3), CEBPA (3/3) and ASXL1 (3/3). The most common adverse events (AEs) during VEN+ HMAs+ half-dose CAG therapy were persistent cytopenias and infections.

Conclusion

The results of this study confirm that VEN+ HMAs+ half-dose CAG is associated with promising efficacy (even high-risk molecular patterns) and tolerable safety profile in patients with unfit or R/R AML. Yet, the study involves only a small sample size, which should not be overlooked. As such, further studies on the efficacy of VEN combined with HMAs and half-dose CAG regimen in AML patients are essential.

Keywords:

• acute myeloid leukemia
• BCL2 inhibitor
• venetoclax
• combined chemotherapy

Abbreviations

AML, acute myeloid leukemia; BFI, breakthrough fungal infection; TLS, tumor lysis syndrome; VEN, venetoclax; AEs, adverse events; R/R, relapsed/refractory; HSCT, hematopoietic stem cell transplant; BCL2, B-cell leukemia/lymphoma-2; HMAs, hypomethylating agents; LDAC, low-dose cytarabine; HD, high-dose; DAC, decitabine; AZA, azacitidine; ELN, European Leukemia Net; WBC, white blood cell; PLT, platelet; CTCAE, Common Terminology Criteria for Adverse Events; MRD, minimal residual disease; CR, complete response; cCR, composite complete remission; PR, partial response; TF, treatment failure; ANC, absolute neutrophil cell; ORR, overall response rate; BM, bone marrow.

Data Sharing Statement

All data generated or analyzed during the research are included in this article. Further enquiries can be directed to the corresponding author.

Ethical Approval

This study protocol was discussed and approved by the Medical Ethics Committee of the First Affiliated Hospital of Harbin Medical University, and the informed consent was approved to be waived in this retrospective analysis by the committee. The study was conducted in compliance with the Declaration of Helsinki, and patient data were maintained with strict confidentiality.

Disclosure

There is no competing interest among the authors.

Additional information

Funding

No funding was received.