(052) Cost Estimation of Concomitant Venetoclax and Azole Therapies in Patients with Acute Myeloid Leukemia

Poster Abstract: Background
Acute myeloid leukemia (AML) is the most common acute leukemia in adults, with a median age of diagnosis of 68 years.1-3 Standard induction for patients unfit to receive intensive chemotherapy includes lower intensity chemotherapy in combination with venetoclax, a potent and selective B-cell lymphoma (BCL-2) inhibitor that is predominantly metabolized hepatically through CYP3A4. 3-6 The most common adverse effects include thrombocytopenia, neutropenia, anemia, and GI upset. 5-7 In addition to the clinical adverse effects associated with venetoclax, the cost of this agent is associated with significant financial toxicity and can be burdensome to patients and their families.8
      Patients with AML are at heightened risk of opportunistic infections including invasive fungal infections (IFI) due to impaired bone marrow reserves and myelosuppression secondary to oncology therapies. Therefore, fungal prophylaxis is indicated in all AML patients undergoing induction.7,9-11 Posaconazole has specifically demonstrated treatment related mortality benefit in AML patients, however, any broad-spectrum azole or echinocandin may be utilized in clinical practice.11 Posaconazole and voriconazole are strong inhibitors of CYP3A4 and therefore interact with venetoclax. This interaction delays clearance of venetoclax and requires dose reduction. Current pharmacokinetic data suggests at least a 75% dose reduction in venetoclax, however, dose reductions can vary in clinical practice.7 Additionally, this drug interaction leads to potentially significant differences in the cumulative dose of venetoclax utilized, therefore affecting the overall cost of therapy. A study has not evaluated whether this drug-drug interaction can be utilized as a cost savings strategy in AML patients receiving venetoclax.

Objectives
The primary objective of this study is to determine the average cost of venetoclax plus antifungal therapy in the presence or absence of concomitant azole antifungals. Key secondary objectives include the dose-intensity and the number of patients who achieve a complete response or complete response with incomplete hematologic recovery after 100 days of concomitant venetoclax and antifungal therapy.

Methods
This is a retrospective cohort study utilizing electronic medical record review of adult patients diagnosed with AML and treated with venetoclax and an antifungal for at least 100 days between April 1, 2016 and June 30, 2022. Data will be collected for each patient starting on day 1 of induction therapy with venetoclax and ending 100 days after venetoclax initiation. For cost analysis, wholesale acquisition cost will be collected by cross referencing the NDC utilized in Micromedex Redbook.

Results
Results pending.

Conclusion
Conclusion pending.

References (must also be included in final poster): 1. Döhner H, Weisdorf DJ, Bloomfield CD. Acute Myeloid Leukemia. N Engl J Med. 2015;373(12):1136-1152. doi:10.1056/NEJMra1406184
2. American Cancer Society. Cancer Facts & Figures 2023. Atlanta, Ga: American Cancer Society; 2023.
3. Alon Rozental, Shai Shimony, Pia Raanani, Ofir Wolach; Analysis of Elderly Patients (≥70 years old) with Acute Leukemia in the Era of Targeted Therapy. Blood 2019; 134 (Supplement_1): 5100. doi: https://doi.org/10.1182/blood-2019-121904
4. DiNardo CD, Pratz K, Pullarkat V, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7-17. doi:10.1182/blood-2018-08-868752
5. 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
6. Guerra VA, DiNardo C, Konopleva M. Venetoclax-based therapies for acute myeloid leukemia. Best Pract Res Clin Haematol. 2019;32(2):145-153. doi:10.1016/j.beha.2019.05.008
7. Agarwal SK, DiNardo CD, Potluri J, et al. Management of Venetoclax-Posaconazole Interaction in Acute Myeloid Leukemia Patients: Evaluation of Dose Adjustments. Clin Ther. 2017;39(2):359-367. doi:10.1016/j.clinthera.2017.01.003
8. Kishan K. Patel, Amer M. Zeidan, Rory M. Shallis, Thomas Prebet, Nikolai Podoltsev, Scott F. Huntington; Cost-effectiveness of azacitidine and venetoclax in unfit patients with previously untreated acute myeloid leukemia. Blood Adv 2021; 5 (4): 994–1002. doi: https://doi.org/10.1182/bloodadvances.2020003902
9. Rausch CR, DiNardo CD, Maiti A, et al. Duration of cytopenias with concomitant venetoclax and azole antifungals in acute myeloid leukemia. Cancer. 2021;127(14):2489-2499. doi:10.1002/cncr.33508
10. Rausch CR, DiPippo AJ, Jiang Y, et al. Comparison of Mold Active Triazoles as Primary Antifungal Prophylaxis in Patients With Newly Diagnosed Acute Myeloid Leukemia in the Era of Molecularly Targeted Therapies. Clin Infect Dis. 2022;75(9):1503-1510. doi:10.1093/cid/ciac230
11. Cornely OA, Maertens J, Winston DJ, et al. Posaconazole vs. fluconazole or itraconazole prophylaxis in patients with neutropenia. N Engl J Med 2007; 356:348–59.