Background: Venetoclax (Ven) in combination with Azacitidine (AZA) is the standard of care for newly diagnosed or relapsed/refractory (R/R) patients with Acute Myeloid Leukemia (AML) aged 75+ or unfit for intensive chemotherapy. The registration VIALE-A trial mandated inpatient therapy initiation, due to the risks of Tumor Lysis Syndrome (TLS) and infection. To enhance patient quality of life, reduce the risk of hospital-acquired infections and alleviate healthcare costs, our study investigates the feasibility of administering the first cycle of therapy in an outpatient setting.

Aims and Methods: This is a retro-prospective single-center study. Inclusion criteria encompassed newly diagnosed or R/R AML patients, aged 18+, receiving their first cycle of Azacitidine-Venetoclax and treated in either an inpatient or outpatient setting at our center. Therapy regimen followed standard guidelines.

All received TLS prophylaxis with rasburicase and/or allopurinol depending on baseline uric acid levels and TLS risk. Our primary endpoint was to evaluate differences in infection and TLS rates between inpatient and outpatient setting, with infection defined as any condition requiring antibiotic therapy (either intravenous or oral) other than anti-infectious prophylaxis, while TLS was defined according to Cairo-Bishop Criteria (Cairo MS, Bishop M, Br J Haematol). Secondary endpoints were evaluation of differences in Overall Survival (OS) and Progression Free Survival (PFS) between the two cohorts. Statistical analysis was performed with Graphpad Prism V 10.2.

Results: Thirty-seven consecutive patients (21 males, 16 females; median age 72 years, range 34-80) diagnosed between June 2020 and May 2024 were included in the study. Among these, 30 patients (81.1%) had newly diagnosed AML, while 7 patients (18.9%) had R/R AML. Eighteen patients (48.6%) received their first cycle of Azacitidine-Venetoclax (C1 AZA-Ven) in an outpatient setting (outpts), whereas 19 patients (51.4%) were hospitalized at the time of therapy initiation (inpts). The two cohorts were well balanced, with no statistically significant differences in sex, karyotype complexity, hemoglobin (Hb), leukocytes, neutrophils, platelets, and creatinine levels at diagnosis. However, outpts were older than inpts, with a median age of 75 years (range 67-80) compared to 66 years (range 34-75) for inpts (p<0.01).

Median time from diagnosis to treatment was 20 days (Confidence Intervals (CI) 9-35 days) for inpts and 27 days (CI 20-40) for outpts.

Regarding the primary endpoint of infection rates, no significant differences were observed between outpts and inpts (38.9% vs. 52.6%, respectively; Odds Ratio 1.7; CI 0.47 to 5.92; p=0.52). Additionally, there were no significant differences in the occurrence of TLS (p=0.48), thus meeting the primary endpoint. Cox-regression analysis with a 30-day censoring revealed no increased Hazard Risk (HR) of infection in outpts compared to inpts (HR 0.71; CI 0.2-1.8; p=0.48). Three (42.8%) of the 7 infected outpts were hospitalized within 7 days from the start of C1 AZA-Ven, while 2 (28.6%) within 30 days. Hospitalizations were primarily for intravenous antibiotic therapy, except for one case of invasive cryptococcal infection.

Considering baseline patients features, only Hb resulted in a higher risk of infection, with infected patients having lower median Hb levels (median 8.6 vs. 10.15 g/dL; p=0.019). No differences were seen in leukocytes, neutrophils and platelet count between infected and not infected patients.

Regarding secondary endpoints, between the two cohorts there was no significant difference in OS at 12 months (inpts: 51.6%, CI 21.6-74.5; outpts: 40.5%, CI 15.2-64.8; p=0.75) or PFS (median PFS: inpts not reached; outpts 21.14 months; p=0.59).

Conclusions: Our preliminary results, based on a retro-prospective analysis, suggest that outpatient administration of C1 AZA-Ven could be a viable alternative to inpatient care, potentially improving patient quality of life and reducing healthcare costs. Further studies with larger sample sizes are warranted to confirm these findings and to identify patients suitable for therapy initiation in an outpatient setting and to determine what baseline characteristics, if any, can aid in risk stratification for TLS or early hospitalization.

Disclosures

No relevant conflicts of interest to declare.

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2024
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