(216) Safety of Venetoclax in Combination with a Hypomethylating Agent for the Treatment of Newly Diagnosed Acute Myeloid Leukemia in Hospitalized Patients

Poster Abstract:

Background: Venetoclax in combination with a hypomethylating agent is a commonly used regimen for patients with acute myeloid leukemia (AML) ineligible for intensive chemotherapy. Due to concerns over life-threatening complications secondary to tumor lysis syndrome (TLS), thrombocytopenia, and neutropenia, patients started on this regimen are commonly hospitalized through count recovery.

Objective: The purpose of this study was to evaluate the safety of venetoclax in combination with a hypomethylating agent in hospitalized patients with newly diagnosed AML. The results of this study will help inform the feasibility of an outpatient initiation protocol for this treatment regimen.

Methods: This was a single-center, retrospective study performed at Baptist Hospital of Miami, a 900-bed community hospital with a malignant hematology unit. Patients included in the study were adults 18 years and older with newly diagnosed AML initiated on induction therapy with venetoclax in combination with azacitidine or decitabine while hospitalized from June 1, 2022 through June 1, 2023. The primary endpoint was the rate of laboratory TLS, as assessed by the Howard criteria, within seven days of treatment initiation. Secondary endpoints included the rate of clinical TLS within seven days and the rate of febrile neutropenia within 28 days.

Results: Thirty patients met study criteria and were included in the final analysis. The median age was 73.5 years (range, 32-87) and the median length of hospitalization of 38.5 days (range, 22-96). No cases of laboratory or clinical TLS occurred within seven days of treatment initiation. All patients received antiviral, antibiotic, and antifungal prophylaxis throughout the duration of severe neutropenia, defined as an absolute neutrophil count (ANC) < 500 cells/mcL. Sixteen patients (53.3%) required treatment with non-prophylactic antimicrobials during the study period, with a median time to escalation of prophylactic antimicrobials of 13.5 days (range, 4-23). In a subgroup analysis, higher rates of febrile neutropenia and antimicrobial escalation were observed in patients with baseline bone marrow blast count ≥ 80%, ANC < 500 cells/mcL, or prior cytoreduction.

Conclusions: Inpatient treatment of newly diagnosed AML with venetoclax and a hypomethylating agent resulted in no cases of TLS within 7 days of chemotherapy initiation. For patients without significant comorbidities and no active infections, outpatient initiation with close monitoring may be feasible to decrease the risk of hospital acquired infections, reduce costs to the health system, and improve patient quality of life.

References (must also be included in final poster): 1. DiNardo, C. D., Jonas, B. A., Pullarkat, V., Thirman, M. J., Garcia, J. S., Wei, A. H., Konopleva, M., Döhner, H., Letai, A., Fenaux, P., Koller, E., … Pratz, K. W. (2020). Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia. The New England Journal of Medicine, 383(7), 617–629.

2. Gangat, N., & Tefferi, A. (2020). Venetoclax-based Chemotherapy in Acute and Chronic Myeloid Neoplasms: Literature Survey and Practice Points. Blood Cancer Journal, 10(11), 122.

3. Palmer, S., Patel, A., Wang, C., Patel, B., Zeidner, J., Foster, M., Muluneh, B., & Buhlinger, K. (2023). Outpatient Initiation of Venetoclax in Patients with Acute Myeloid Leukemia. Journal of Oncology Pharmacy Practice, 29(7), 1590–1598.

4. Papayannidis, C., Nanni, J., Cristiano, G., Marconi, G., Sartor, C., Parisi, S., Zannoni, L., Saed, R., Ottaviani, E., Bandini, L., Testoni, N., Baldazzi, C., Solli, V., Ricci, P., Di Giovanni Bezzi, C., Abd-Alatif, R., Stanzani, M., Paolini, S., Cavo, M., & Curti, A. (2022). Impact of Infectious Comorbidity and Overall Time of Hospitalization in Total Outpatient Management of Acute Myeloid Leukemia Patients Following Venetoclax and Hypomethylating Agents. European Journal of Haematology, 108(6), 449–459.

5. Pelcovits, A., Moore, J., Bakow, B., Niroula, R., Egan, P., & Reagan, J. L. (2021). Tumor Lysis Syndrome Risk in Outpatient versus Inpatient Administration of Venetoclax and Hypomethylators for Acute Myeloid Leukemia. Supportive Care in Cancer, 29(9), 5323–5327.