(237) Use of Venetoclax Plus Cladribine, Idarubicin, and Cytarabine as Induction Chemotherapy for De Novo or Relapsed/Refractory Acute Myeloid Leukemia: A Single Center Experience

Poster Abstract: Background/Rationale: Standard induction chemotherapy in acute myeloid leukemia (AML) is comprised of cytarabine and either daunorubicin or idarubicin (IDA). This regimen has demonstrated complete remission rates averaging 60%(1); despite this, approximately 30-40% of patients relapse after frontline therapy.(2,3) Modifications have been made to intensive chemotherapy in efforts to improve patient outcomes and complete remission rates. A phase 1/2 study by DiNardo and colleagues evaluated the use of fludarabine, cytarabine, granulocyte colony-stimulating factor, IDA, and venetoclax (FLAG-IDA-VEN).(4) FLAG-IDA-VEN demonstrated a composite complete response (CR) rate of 76% with 96% of de novo (DN) and 69% of relapsed/refractory (R/R) patients achieving measurable residual disease (MRD)-negative status.(4)
Since this publication, select patients at the University of Virginia (UVA) Health have received FLAG-IDA-VEN induction in the DN or R/R setting. However, due to a nationwide fludarabine shortage in December 2021, UVA established a fludarabine sequestration plan. During the fludarabine shortage at UVA, candidates for FLAG-IDA-VEN induction received an alternative induction regimen utilizing cladribine, IDA, cytarabine, and VEN (CLIA-VEN) for DN or R/R AML. The use of this regimen was supported by a phase 2 study by Kadia and colleagues evaluating CLIA-VEN in DN-AML patients.(5) CLIA-VEN demonstrated a composite CR rate of 96% with 82% of patients achieving undetectable MRD.(5) This institutional review was conducted after approximately 2 years of CLIA-VEN induction use in these select patients.

Objective: To evaluate safety and efficacy of CLIA-VEN as induction chemotherapy for DN or R/R AML patients at UVA Health.

Methods: This retrospective, single-center, cohort study included adult patients ≥ 18 years of age with DN or R/R AML who received CLIA-VEN for induction chemotherapy from December 2021 through September 2023. Data were obtained through an electronic health record report and manual chart review. The primary outcome assessed the composite rate of patients attaining CR and CR with incomplete hematologic recovery (CRi). Secondary outcomes included percent of patients achieving MRD-negative status, duration of response, overall survival, time to absolute neutrophil count recovery, and length of hospitalization. Data pertaining to those who proceeded to stem cell transplant were also collected. Safety outcome measures included the development of cardiotoxicity, pulmonary toxicity, hepatotoxicity, and infectious complications. Data were analyzed using descriptive statistics.

Results: Results are pending.

Conclusion: Conclusion is pending.

References (must also be included in final poster): 1. Rai KR, Holland JF, Glidewell OJ, et al. Treatment of acute myelocytic leukemia: a study by Cancer and Leukemia Group B. Blood. 1981;58(6):1203-1212.
2. Fernandez HF, Sun Z, Yao X, et al. Anthracycline dose intensification in acute myeloid leukemia. N Engl J Med. 2009;361(13):1249-1259.
3. Löwenberg B, Ossenkoppele GJ, van Putten W, et al. High-dose daunorubicin in older patients with acute myeloid leukemia. N Engl J Med. 2009;361(13):1235-1248.
4. DiNardo CD, Lachowiez CA, Takahashi K, et al. Venetoclax combined with FLAG-IDA induction and consolidation in newly diagnosed and relapsed or refractory acute myeloid leukemia. JCO. 2021;39(25):2768-2778.
5. Kadia TM, Reville PK, Borthakur G, et al. Venetoclax plus intensive chemotherapy with cladribine, idarubicin, and cytarabine in patients with newly diagnosed acute myeloid leukaemia or high-risk myelodysplastic syndrome: a cohort from a single-centre, single-arm, phase 2 trial. The Lancet Haematology. 2021;8(8):e552-e561.