Assessing Overall Survival, Quality of Life, Frailty, Comorbidity Indexes, Healthcare Usage, and Pharmacoeconomics in Elderly Patients with Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is a malignant disease of the bone marrow with a
poor prognosis, especially in elderly patients [1][2]. With a year incidence of
3 - 4,5 cases per 100.000 people AML is a rare disease although it is the most
frequently diagnosed leukemic disease [3]. As the median age at diagnosis is 68
years, AML at a young age is viewed as a different disease entity [1][2][3].
Patients aged below 65 are commonly treated by intensive induction chemotherapy
until remission or remission with minimal residual disease is reached.
Remission, if reached, is then consolidated with an allogenic or autologic stem
cell transplant. Elderly patients are often times not in a good enough baseline
health state to undergo this highly intensive, somewhat risky, and overall
expensive treatment trajectory [1][3]. In 2012 and 2015 respectively the
Hypomethylating agents Azacitidine and Decitabine were introduced to the market
and offer less intensive treatment options for elderly patients [4][5]. Because
of this, stratifying de novo AML patients into the follow three groups became
common practice: Fit for intensive chemotherapy, not fit for intensive
chemotherapy but fit enough for HMA based therapy, and unfit even for HMA based
therapy [6]. After a period in which Azacitidine monotherapy was the first
choice of treatment for patients deemed ineligible for intensive induction
therapy, the combination of Azacitidine AZA with Venetoclax VEN was proven to
lead to superior outcomes and has been promoted to first choice of treatment
for this patient group in March 2022 [7]. In the near future, multiple other
agents currently in phase III clinical trials are expected to make it into
treatment guidelines [8][9].
The superiority in terms of OS of the HMA with VEN combination regimens over
HMA comes with more side effects, adverse events, nights stayed in the hospital
(time toxicity), as well as increasing healthcare costs. It is unknown how
Quality of Life (QOL) develops in AML patients under the novel regimens in the
real world setting [10]. It would be highly desirable to be able to predict
which patients develop toxicity to better identify patients that might benefit
from regimens such as AZA+VEN There are multiple prognostic tools for
evaluation of certain conditions and interventions already validated in AML
populations (Ferrara criteria, Wheatley Index, HCT-CI, AML-CM, and more being
developed) [6][11][12]. It is unknown however how valuable these tools are for
aiding clinical decision-making. It is also not well known what other costs
-besides the substantial cost of agents such as Venetoclax- the new regimens
creates through increases in healthcare usage.

Primary Objective:
- To assess and describe Quality of Life throughout a patients treatment
trajectory

Secondary Objective(s):
- To assess and describe how frail unselected real world AML patients are at
diagnosis using geriatric screening tools (G8, 6-CIT) and comorbidity tools
(HCT-CI, AML-CM, Ferrara criteria lists, Wheatley Index, Charlson Comorbidity
Index CCI)
- To determine of what predictive quality of clinical scoring tools (Ferrara,
Wheatley, HCT-CI, AML-CM) are for endpoints such as overall survival, 1-year
survival, remission rates, rates of treatment related mortality, and early
death (within 30 days)
- To evaluate the potential of the Wheatley Index, the HCT-CI, and the AML-CM
for usage as a tool to support choosing between non-intensive chemotherapy and
best supportive care in AML
- To analyze how an AML patients QOL changes in respect to time and in respect
to treatment regimens
- To quantify healthcare usage (transfusions, antibiotics, other) of elderly
patients with AML.
- To evaluate the AZA+VEN regimen from a pharmaco-economical perspective (ICER,
price per QALY) by combining the survival-, quality of life-, and healthcare
usage data and comparing it to existing data on Azacitidine monotherapy

The ZEALOUS-AML study is a prospective, observational, single-centre, real
world study. The investigators are exploring options for collaboration with
other STZ hospitals. The inclusion period of the study is 2,5 years (between
01-01-2023 and 31-06-2025). The design was chosen for its real world
representativeness, aiming for inclusion of at least 50 patients in the Medisch
Centrum Leeuwarden. Assessment of comorbidity scores requires access to a
patients full medical history. Quantification of healthcare usage and
pharmacoeconomic evaluation require extensive data gathering during a patients
trajectory. All datapoints collected are required for the analysis. An interim
pharmacoeconomic analysis may commence as early as when the 15th included
patient passed away.

The study is mainly observational in nature with questionnaires for patients
(before cycle 1, after cycle 1, after cycle 2, after cycle 4, 6, 8, *) and
family (2-4 weeks after death of the patient) being the only interventions. AML
patients spend considerable time in the hospital anyways, especially during the
first cycle. We deem the risk for patients to be zero and the burden for
patients to be acceptable with each questionnaire taking approximately 30
minutes of their time. The burden for the family is potentially significant as
they are approached with an optional request in a difficult time of their life,
that however only takes 5-15 minutes to answer.