Predictors of Mortality Among Acute Myeloblastic Leukemia Patients Using Venetoclax with Septicemia

Introduction: With scientific growth and the development of groundbreaking therapies, the prognosis of acute myeloblastic leukemia (AML) has improved over the last decades. Venetoclax, a novel therapy that targets BCL-2 inhibition, has recently been approved for use among AML patients. As with several other oncological treatments, Venetoclax can lead to multiple hematologic toxicities that predispose them to infection and septicemia. We aim to evaluate the all-cause mortality among AML patients using Venetoclax who were admitted for septicemia through a national estimate.

Methods: Our retrospective study consisted of adults (≥18 years) with AML(excluding remission) using Venetoclax who experienced septicemia from the 2019-2021 National Inpatient Sample(NIS). The mortality rate was calculated. We applied multivariable regression analyses to understand the roles of various patient characteristics and complications in their all-cause in-hospital mortality. We reported them as adjusted odds ratios, 95% confidence intervals, and their p-values[aOR[95%CI, p-value].

Results: In total, 720 adults matched our selection. The mortality rate was estimated at 22.2%, as it included 160 deaths among patients who also expressed a higher median age (71.00 years, IQR 61.25-76.00, vs. 65.00 years, IQR 53.25-72.00, p<0.01). While females (aOR 0.503[0.262-0.966,p=0.039]) had lower odds of death than males, no differences were seen for weekend (vs. weekday, aOR 0.551[0.192-1.582,p=0.268]) admissions, and for patients covered by Medicaid(aOR 0.326 [0.096-1.112, p=0.074]) or private insurance(aOR 0.544[0.244-1.215, p=0.138)(vs. Medicare). Racial disparities were noted with higher odds of mortality among Blacks(aOR 2.593[2.247-13.924], p<0.01) and Hispanics(aOR 5.549[2.248-13.697, p<0.01]), as compared to Whites. Comorbidities including obesity(aOR 3.636[1.369-9.659, p=0.010]) and chronic obstructive pulmonary disease (COPD)(aOR 6.501 [2.253-18.760, p<0.01]) were linked with poorer outcomes. At the same time, no differences were seen for hypertension(aOR 0.501,p=0.077), diabetes(aOR 0.767,p=0.502), dyslipidemia(aOR 0.807, p=0.513), chronic kidney disease(CKD)(aOR 0.542,p=0.091), or peripheral vascular disease(PVD)(aOR 1.910, p=0.235). Paradoxically, patients with pancytopenia/anemia/agranulocytosis had reduced odds of death(aOR 0.40[0.220-0.731, p<0.01]). Events involving tumor lysis syndrome(TLS) [aOR 2.471[1.128-5.412, p=0.024]), acute kidney injury (AKI)(aOR 5.663[2.756-11.637, p<0.01]), or cardiac arrest(aOR 7.745[1.604-37.402, p<0.01]) also were more likely to lead to death. No differences were seen for those who experienced gastrointestinal bleeding (aOR 1.297, p=0.708]), acidosis(aOR 0.544, p=0.106), or disseminated intravascular coagulation (DIC)(aOR 1.765,p=0.312).

Conclusion: Our study highlights the racial and sex-based disparities in mortality among our sample. Moreover, several events and comorbidities were also linked with poorer outcomes. The presence of lower mortality odds among patients with pancytopenia/anemia/agranulocytosis is potentially linked with close monitoring and early admissions in such cases. As the NIS does not provide data on the main cause of death, physicians and researchers need to develop additional studies to identify the key risk factors and develop adequate measures to improve their outcomes.