Statistical Analysis
Total cost and utilization were summarized for the cohort for the 90-day
time period of interest. Cost was further characterized by the location
of service provided, the presence of ICD-10 codes for the complications
of CRS (D89.831-D89.835, D89.839) and/or ICANS (G92.00-G92.05). Total
cost was analyzed by age group (1-9 years vs. 10-25 years) as a proxy
for upfront ALL risk group and by the occurrence of CRS. Analyses were
performed using R.33
Results
A cohort of 37 patients aged 1-25 years was identified with a
concomitant ICD-10 code for ALL and CPT code for CAR-T cell
administration (Table 1). All patients had continuous coverage
enrollment from one month prior to infusion through two months
post-infusion except patients who died during the time period. Thirteen
patients (35%) were under 10 years of age at the time of cell infusion;
median age at administration was 13 years (interquartile range [IQR]
7-19 years). Fourteen patients (37.8%) were female, and while 14
patients were reported to be White, race and ethnicity were unknown in
43% of individuals.
Over the 90 day period encompassing 30 days prior to CAR-T infusion
through 60 days post-infusion, the median cost for the full cohort was
$620,500 (mean, $585,398). Overall utilization and cost findings are
shown in Table 2. Median cost was not significantly different between
patients under vs. over age 10 ($620,279 vs $633,137, respectively).
Inpatient cost accounted for approximately 71% of the total cost with a
median inpatient cost of $556,492. Median outpatient cost was $70,545.
There were no statistically significant differences between inpatient or
outpatient total cost between the two age cohorts (Figure 1).
The median number of inpatient encounters across the cohort was 2, with
patients spending a median of 21 days in the hospital. Patients had an
average of 7 outpatient visits in the 30 days prior to CAR-T therapy and
an average of 9 outpatient visits in the 60 days following infusion.
Similar to cost, there was no significant difference between the
utilization of care based on age.
Within the cohort, less than 11 patients had a diagnostic code for
cytokine release syndrome at some point during the study period
(n<11 cannot be identified per OptumLabs data guidelines). No
patients in the dataset had a diagnostic code for ICANS. When stratified
into CRS and non-CRS cohorts, there were no significant differences in
total, inpatient or outpatient cost between the cohorts (Figure 2).
Greater than zero but less than 11 patients had a diagnosis code
indicative of death during the 60 days post-infusion.
Discussion
In this study, we examined the healthcare cost and utilization for
pediatric patients receiving CAR-T cell therapy for B-ALL using a
commercial claims database, the first analysis of its kind in this
patient population. Patients were predominantly male and most were
adolescents, which is consistent with prior studies that have shown that
in the pediatric population, male sex and age >10 years are
significant predictors of inferior post-relapse survival and therefore
require novel therapies such as CAR-T.34
Almost all patients received the CAR-T therapy in the inpatient setting,
and thus, inpatient cost was significantly higher than outpatient cost,
likely reflecting the price of the tisagenlecleucel product itself in
addition to the cost of lymphodepleting chemotherapy and care for
post-infusion complications. Costs of emergency department care and home
health-related care contributed minimally to the overall cost burden in
the 90 day period of interest around CAR-T infusion.
The median total cost across the entire cohort for the period of
interest was $620,500, indicating that the typical cost of care,
excluding the listed drug price for tisagenlecleucel of $475,000, was
approximately $145,500. This is fairly consistent with cost modeling
performed for tisagenlecleucel in pediatric B-ALL patients by Lin et al.
which predicted the total cost to be between $548,000 and
$599,000.18 This is also consistent with other
reports of cost associated with the real-world care for patients
receiving CAR-T therapies in adults with relapsed or refractory
lymphomas.35,36
Our study has several limitations. The landmark ELIANA trial of
tisagenlecleucel study reported a CRS rate of 77% and neurotoxicity
rate of 40% with this therapy.8 Prior to October
2020, no ICD-10 diagnosis codes for CRS or ICANS had been adopted by the
Centers for Medicare & Medicaid Services. Therefore, other studies have
utilized claims-based algorithms for CRS and neurotoxicity via expert
clinical opinion and based on the clinical manifestations of these
complications.35 However, given the lack of ability to
validate these algorithms with electronic medical record (EMR)-based
records, the interpretation of these algorithms is challenging. Less
than 11 patients in our cohort had a recorded ICD-10 for cytokine
release syndrome (CRS) and no patients had a diagnostic code for
immune-effector cell associated neurotoxicity syndrome (ICANS). This is
expected given the cohort was primarily treated prior to October 2020
when ICD-10 codes for these diagnoses were introduced, however it
unfortunately impacts our ability to detect whether there was higher
cost and utilization of care for patients with vs without CRS. Cost that
may not have been captured in this analysis include those of
leukapheresis, which often occurs greater than 30 days prior to the
administration of the CAR-T product, as well as the longer term cost of
B-cell aplasia and secondary hypogammaglobulinemia following CAR-T
infusion, treated with immune globulin replacement therapy.
Consistent with most commercial claims databases, some demographic and
clinical characteristics, such as race/ethnicity or prior therapies such
as stem cell transplant, were absent or missing from the OptumLabs
data.35 This limits our ability to analyze the effect
of race/ethnicity on cost, a key component of health equity and
opportunity in the current era of healthcare in the United States. The
relatively small sample size of this study limits the power to detect
differences between cohorts and the lack of clinical information or
ability to validate diagnostic coding with EMR-based data limits
analysis of the effect of disease characteristics, performance index or
prior therapies and hinders cost-benefit analyses. Additionally, the
OptumLabs Data Warehouse is limited to commercially insured individuals,
thus excluding publicly insured or managed care patients from this
analysis and limiting the generalizability of these results.
Conclusions
This robust real-world cost analysis shows for the first time the true
cost and peri-infusion care utilization of CAR-T therapy for pediatric
B-ALL. This encompasses not only the commercial cost of the cellular
therapy product itself, but the care involved prior to cell product
infusion and the management of its complications. The total cost and
utilization of care is not significantly impacted by patient age. Mean
and median total cost well exceeded $500,000 US dollars, as expected
with the listed commercial price of tisagenlecleucel of $475,000. This
study provides a valuable benchmark that can be used to analyze the
financial toxicity of CAR-T therapy for pediatric ALL therapy on health
systems, patients and families. The cost of this therapy can be
reassessed over time as other novel therapeutics are introduced into ALL
therapy and long-term outcome data for this therapy are established
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TABLE 1 Demographics