Venetoclax Combined with Cladribine, Idarubicin, Cytarabine Shows Promise in Patients with Newly Diagnosed AML, High-Risk MDS

By Leah Sherwood - Last Updated: December 27, 2022

Among younger patients with newly diagnosed acute myeloid leukemia (AML) deemed fit for intensive chemotherapy, venetoclax with cladribine, idarubicin, and cytarabine (CLIA) induced high rates of minimal residual disease (MRD)-negative remissions, allowing a higher rate of these patients to proceed with a potentially curative allogeneic hematopoietic stem cell transplantation (HSCT), according to updated results and longer-term follow-up of a phase II study.

The results on the study of venetoclax plus CLIA in this population were presented at 2022 American Society of Hematology Annual Meeting and Exposition in a poster session by Patrick K. Reville, MD, MPH, of the University of Texas MD Anderson Cancer Center, and colleagues.

The ongoing clinical trial is investigating venetoclax combined with CLIA for patients aged 65 years or younger with newly diagnosed AML or high-risk myelodysplastic syndromes (MDS). Induction included intravenous (IV) cladribine 5 mg/m2 on days one through five, cytosine arabinoside 1.5 g/m2 IV on days one through five, and idarubicin 10 mg/m2 IV on days one through three; venetoclax was given at an effective dose of 400 mg on days two to eight without ramp up with every cycle. Consolidation consisted of three days of cladribine, idarubicin, and cytarabine (two days of idarubicin).

A total of 67 patients were treated with venetoclax plus CLIA. The median patient age was 48 years (range, 18-64 years). Among these patients, 60 had a diagnosis of AML, four had high-risk MDS (either high or very high risk by Revised International Prognostic Scoring System), and three patients had a mixed phenotype acute leukemia with a myeloid predominant clone.

All patients who received venetoclax plus CLIA were evaluable for response, with a composite complete response rate (CRc) of 96%. The best response was CR in 57 (85%), complete remission with incomplete count recovery (CRi) in seven (10%), no response in two (3%), and death in one (2%) patient.

In responding patients with a bone marrow sample that was evaluable for assessment of measurable residual disease (MRD) by flow cytometry, 55 of 61 patients (90%) were MRD-negative.

Responses were preserved across European Leukemia Network (ELN) risk classification groups with the CRc (CR/CRi) rate of 94% (88%/6%), 95% (86%/9%), and 96% (84%/12%) for patients with ELN favorable, intermediate, and adverse risk, respectively.

With a median follow up of 22.5 months, the median duration of response (DOR) was not yet reached, with an estimated 12- and 24-month DOR of 82.6% and 80.3%, respectively. The median EFS was not yet reached with an estimated 12- and 24-month EFS of 71.8% and 69.7%, respectively. The median overall survival (OS) was not yet reached, with an estimated 12- and 24-month OS of 86.5% and 70.7%, respectively.

“EFS and OS rates are highly encouraging and worthy of further study as a safe and effective induction treatment strategy for younger patients with AML or high-risk MDS,” the authors concluded.


Reville PK, Kantarjian H, Borthakur G, et al. Venetoclax combined with cladribine, idarubicin, cytarabine (CLIA) as induction therapy in patients with newly diagnosed acute myeloid leukemia and high-risk myelodysplastic syndrome. Abstract #709. Presented at the 64th American Society of Hematology Annual Meeting, December 10-13, 2022; New Orleans, Louisiana.

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