Venetoclax Plus Hypomethylating Agents Demonstrated Improved Outcomes and Infection Risk Among Older Patients With Acute Myeloid Leukemia

For the treatment of acute myeloid leukemia among adult patients over the age of 65 years, venetoclax combined with hypomethylating agents demonstrated favorable safety and efficacy compared with standard and low-dose chemotherapy, according to a retrospective analysis published in the American Journal of Cancer Research.

Previous research has highlighted the need for additional treatment options for patients with AML that are over the age of 60 years. The combination of anthracyclines and cytarabine as a chemotherapy option for AML has demonstrated a need reduced overall survival (OS) and complete remission (CR) among patients over 60, as well as increased risk for infections. Additionally, BCL-1 oral inhibitors, such as venetoclax, can increase AML cell sensitivity and improve tumor cell apoptosis.

While no current standardized therapy exists for AML, researchers conducted a retrospective study to evaluate the infection profiles and characteristics of elderly patients with AML undergoing initial induction therapy under various therapies, including standard chemotherapy lines and venetoclax.

Researchers analyzed the medical records of 169 eligible patients with AML who had not received any lines of prior therapy. Patients were stratified according to treatment regiments including standard chemotherapy (e.g., idarubicin plus cytarabine; n = 84), low dose chemotherapy (i.e., cytarabine plus aclarubicin; n = 53), and targeted therapy with venetoclax combined with hypomethylating agents (n = 32). The primary outcome was infection incidence and AML response was a secondary outcome.

Overall, patients who were assigned to targeted venetoclax therapy (73 years) were older than patients receiving standard chemotherapy (68 years) and low dose chemotherapy (71 years). Additionally, patients receiving venetoclax (87.5%) were more likely to have comorbidities including hypertension and diabetes compared with patients receiving standard chemotherapy (46.4%) or low dose chemotherapy (58.5%; P < .05).

Among all patients, complete response was seen in 79 patients. Overall response rates (ORR) were higher for patients who received targeted therapy than patients who received standard chemotherapy or low dose chemotherapy (68.8% vs 51.2% vs 26.4%, P=.0004).

Patients in the targeted group experienced shorter duration of neutropenia (9.0 ± 8.4 days) than patients under standard chemotherapy (15.0 ± 15.0 days) and patients who received low dose chemotherapy (9.2 ± 9.1 days; P <. 05). Additionally, fever duration was shorter under targeted therapy compared with standard chemotherapy and low dose chemotherapy (2.34 ± 3.59 vs 4.52 ± 4.38 vs 3.53 ± 4.76 days; P < .05).

Infections occurred in 159 patients, with an overall infection rate of 93.5%. Some of the most common infections were lung infections (70.53%), bloodstream infections (6.8%), upper respiratory tract infections (4.2%), and skin infections (4.2%). Infection rates were lower among patients who received targeted therapy (87.5%) than patients who received standard chemotherapy (95.2%) or low dose chemotherapy (94.3%; P <. 05).

A significantly lower number of patients who received targeted therapy (34.4%) initiated preemptive antifungal prophylaxis compared to patients in the standard chemotherapy group (48.8%) or the low-dose chemotherapy group (43.4%).

Septic shock was experienced by 1 patient, as well as 2 patients who progressed to functional failure stage via infection-induced multiple organse dysfunction syndrome.

“Compared with standard and low dose chemotherapy, targeted therapy combining VEN (venetoclax) and HMA (hypomethylating agents) improves disease remission rates in elderly AML patients,” the researchers concluded, “Additionally, the targeted therapy has a favorable safety profile with a lower incidence and severity of infections.”

Source:

Zhu W. Safety and infection risk factors in elderly acute myeloid leukemia patients undergoing induction therapy with venetoclax combined with hypomethylating agents. American Journal of Cancer Research. Published online December 15, 2024. doi: 10.62347/vzzv6163