(236) Use of Venetoclax in Combination with Hypomethylating Agents for the Treatment of Myelodysplastic Syndrome

Poster Abstract:

Background:
Acute myeloid leukemia (AML) is diagnosed based on the presence of ≥20% blasts in the bone marrow. Those with blasts present but making up < 20% of the cellularity are diagnosed with myelodysplastic syndrome (MDS). Historically, this differentiation in diagnosis has limited patients with 10%-19% of bone marrow blasts to the same MDS treatment options used in patients with a very low burden of bone marrow blasts ( < 10%). In 2022, the World Health Organization (WHO) addressed this problem by redefining the classification of MDS, categorizing the disease as “MDS-IB2 (increased blasts)” for patients with 10-19% bone marrow blasts. This WHO update also states that MDS-IB2 may be considered as an equivalent of AML for treatment purposes. However, the National Comprehensive Cancer Network (NCCN) guidelines have not yet taken a firm approach regarding treatment options for these AML-equivalent MDS cases. While combination therapy is most often what is utilized in AML, the NCCN guidelines recommend one of the following for MDS: clinical trial, a hypomethylating agent such as azacitidine (preferred) or decitabine, or allogeneic hematopoietic stem cell transplant if eligible.

In 2020, a phase 3, double-blinded, placebo-controlled trial evaluated azacitidine plus venetoclax compared to azacitidine alone in previously untreated patients with AML that were not able to receive intensive chemotherapy. DiNardo and colleagues report longer overall survival and a higher rate of complete remission with combination therapy. Since MDS with 10-19% blasts can be classified similarly to AML according to the WHO update and current NCCN guidelines, combination therapy with a hypomethylating agent and venetoclax may be one option for these AML-equivalent MDS patients based on the positive results of the 2020 trial.

Objective(s):
The primary objective is to evaluate treatment response in patients diagnosed with high-risk MDS treated with venetoclax and a hypomethylating agent. The secondary objective is to evaluate the safety of combination therapy with venetoclax and a hypomethylating agent in patients with high-risk MDS.

Methods:
This IRB-approved, single center, retrospective study included patients 18 years of age or older with MDS who have received venetoclax and a hypomethylating agent (azacitidine or decitabine) for the treatment of MDS between 1/1/2017 and 9/30/2023. Patients enrolled in a clinical trial were excluded. Data will be collected via chart review from the electronic medical record. All outcomes evaluating treatment response will be defined by the 2006 International Working Group response criteria in myelodysplasia.

Results:
Results pending.

Discussion/

Conclusions:
Results pending.

References (must also be included in final poster): Cheson BD, Greenberg PL, Bennett JM, et al. Clinical application and proposal for modification of the International Working Group (IWG) response criteria in myelodysplasia. Blood. 2006;108(2):419-425. doi:10.1182/blood-2005-10-4149

DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. N Engl J Med. 2020;383(7):617-629. doi:10.1056/NEJMoa2012971

Khoury JD, Solary E, Abla O, et al. The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Myeloid and Histiocytic/Dendritic Neoplasms. Leukemia. 2022;36(7):1703-1719. doi:10.1038/s41375-022-01613-1

NCCN. Acute Myeloid Leukemia NCCN Clinical Practice Guidelines in Oncology. Version 6.2023 – October 24, 2023 https://www.nccn.org/professionals/physician_gls/pdf/aml.pdf

NCCN. Myelodysplastic Syndromes NCCN Clinical Practice Guidelines in Oncology. Version 3.2023 – November 10, 2023. https://www.nccn.org/professionals/physician_gls/pdf/mds.pdf