Epidemiology and Outcomes of Hospitalized Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Patients Who Developed Acute Respiratory Failure

Abstract

Objectives:The aim of the study was to examine the incidence, baseline characteristics, and outcomes of Chimeric Antigen Receptor T-cell (CAR-T) therapy admissions in individuals who developed acute respiratory failure (ARF). The study utilized the National Inpatient Sample (NIS) database for the years 2017 to 2020. Methods: The study identified CAR-T cell therapy hospitalizations through the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes. Patients with acute respiratory failure (ARF) were further classified using specific International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Descriptive statistics were performed to analyze baseline characteristics, comorbidities, complications, and outcomes. Results: Analysis of the NIS Database identified 5545 CAR-T therapy admissions between 2017 and 2020, revealing a rising trend over time. In our study, we found that hypertension (39%), dyslipidemia (21.7%), and venous thromboembolism (13%) were the most frequently observed comorbidities in CAR-T cell therapy admissions. Acute respiratory failure (ARF) was reported in 7.1% of admissions, and they had higher all-cause in-hospital mortality than CAR-T cell therapy admissions without ARF (32.9% vs 1.3%, P < 0.001). ARF admissions that required invasive mechanical ventilation (IMV) also had higher all-cause in-hospital mortality compared to admissions not requiring IMV (48.9% vs 11.8%, P = 0.001). There was no difference in the mortality rate among admissions with non-Hodgkin's Lymphoma, Multiple Myeloma, and Leukemia that utilized CAR-T therapy. Conclusions: In this largest study to date, we illuminate the incidence and outcomes of CAR-T cell therapy admissions with ARF. Higher mortality rates were observed in CAR-T cell therapy admissions with ARF. The study emphasizes the crucial role of interdisciplinary collaboration in CAR-T patient management and calls for additional research to clarify ARF's etiology and inform effective management strategies.

Keywords

CAR-T cell therapy acute respiratory failure outcome assessment

Background

Chimeric Antigen Receptor T-cell (CAR-T) therapy has emerged as a revolutionary modality in the treatment of relapsed and refractory hematological malignancies. This immunotherapeutic approach involves the genetic modification of autologous T-cells to express chimeric antigen receptors, enabling targeted recognition and tumor lysis. Treatment-related complications arising from CAR-T therapy, including cytokine release syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), can progress to life-threatening conditions that require aggressive supportive care and close monitoring in the intensive care unit (ICU).^1,2 It is reported that 15–47% of patients in limited studies required ICU admission.^2-4 There are a few studies describing the characteristics and outcomes of CAR-T cell recipients, including those requiring ICU admission; however, robust, large-scale database studies regarding the incidence and outcomes of CAR-T recipients are lacking.³ Here, we present a large database study on CAR-T cell admissions with a specific focus on acute respiratory failure (ARF).

Objectives

To query a large database to describe the incidence, baseline characteristics, and outcomes of hospitalized CAR-T therapy patients who develop acute respiratory failure.

Study Design and Methods

Data Source

This retrospective cohort study aimed to investigate the factors associated with CAR-T cell therapy and in-hospital mortality. Additionally, the study examined the relationship between CAR-T cell therapy and other socioeconomic and hospital-level factors, such as the length of stay and hospitalization cost. The study utilized the National Inpatient Sample (NIS) database for the years 2017 to 2020, which was developed for the Healthcare Cost and Utilization Project sponsored by the Agency for Healthcare Research and Quality. The NIS is a publicly available all-payer database of inpatient hospitalizations in the United States, providing nationally representative estimates of hospital inpatient stays. It contains a stratified sample of approximately 20% of all discharges from community hospitals in the country, estimating more than 35 million hospitalizations annually. Each observation in the database represents a hospitalization with one primary diagnosis, up to 39 secondary diagnoses, and 25 procedure diagnoses. These are coded using the International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes and International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes. The NIS data are depersonalized, and individual identities are protected. As the study used the NIS database, it was exempt from review by the institutional review board.

Study Population

We utilized the NIS database from 2017 to 2020 to identify hospitalizations with CAR-T cell therapy administration using ICD-10-PCS codes XW033C3, XW043C3, XW23346, XW24346, XW23376, and XW24376. Among these CAR-T cell therapy hospitalizations, the acute respiratory failure subgroup was identified using ICD-10-CM codes J80, J95.821, J95.822, J96.00, J96.01, J9602, J96.20, J96.21, J96.22, and R09.2 listed anywhere in the diagnosis column. The invasive mechanical ventilation subgroup was identified using ICD-10-PCS codes 5A1935Z, 5A1945Z, 5A1955Z, 0BH17EZ, and 0BH18EZ.

Baseline Variables and Comparison Groups

Admissions for CAR-T cell therapy were divided into three groups: non-Hodgkin's lymphoma, multiple myeloma, and leukemia. Additionally, a comparative analysis was conducted on CAR-T cell therapy admissions with and without acute respiratory failure. Baseline variables included demographic characteristics such as age, sex, median household income, and race, with categories of Whites, Blacks, Hispanics, and others (including Asian or Pacific Islanders and Native Americans). Comorbidities (such as hypertension, obesity, venous thromboembolism, cerebrovascular disease, diabetes mellitus) and complications (such as acute kidney injury, acute respiratory failure, neutropenia) were identified using ICD-10-CM codes and the Charlson comorbidity index. The study also investigated the utilization of various procedures, such as non-invasive ventilation and invasive mechanical ventilation, and hospital characteristics, including teaching status, region of the hospital, bed size, and primary payer.

Statistical Analysis

We conducted a descriptive analysis to compare baseline characteristics and in-hospital outcomes among the three groups: non-Hodgkin's lymphoma, multiple myeloma, and leukemia. Additionally, we examined and compared these baseline variables between hospitalizations for CAR-T cell therapy with and without acute respiratory failure. The provided weights were employed to generate national estimates using the methodology outlined by the Healthcare Cost and Utilization Project.⁵ Categorical variables were analyzed using a paired Chi-square test, while means for continuous variables were compared using the adjusted Wald test. The results were presented as percentages for categorical variables and mean ± standard deviation (SD) for continuous variables. The ICD-10 codes utilized in the study can be found in the e-appendix. Furthermore, we reported annual CAR-T cell therapy admissions from 2017 to 2020, along with the corresponding mortality rates for each year. The analyses were conducted using Stata software version 15.1 (StataCorp, College Station, TX).

Results

Baseline Characteristics and outcomes of CAR-T therapy admissions

Between 2017 and 2020, we identified 5545 admissions for CAR-T therapy, with the frequency of CAR-T admissions increasing over time (61 admissions in 2017 to 2120 admissions in 2020) (Figure 1). The baseline characteristics of these admissions are detailed in Table 1. The majority of admissions in our study occurred at teaching hospitals (99.4%), and 41% of these admissions were females. Hypertension (39%), dyslipidemia (21.7%), and venous thromboembolism (13%) were identified as the most prevalent comorbidities in CAR-T cell therapy admissions. Additionally, the most common complications included fever (53.9%), sepsis (39.5%), and neutropenia (38.3%), with ARF occurring in 7.1% of admissions. The mean length of stay was 19 days, and the all-cause in-hospital mortality was 3.5%. Lastly, we found no difference in mortality among admissions with non-Hodgkin's lymphoma, multiple myeloma, and leukemia that underwent CAR-T therapy (P = 0.538). The annual CAR-T cell therapy admissions from 2017 to 2020, along with the corresponding mortality rates for each year are depicted in Figure 1, illustrating an increase in the frequency of CAR-T admissions over time.

Table 1.

Baseline Characters and Outcomes of CAR-T Cell Therapy Admissions.

Variable	All (N = 5545)	Non-Hodgkin's lymphoma (N = 4135)	Multiple myeloma (N = 595)	Leukemia (N = 630)	P value
Age at admission in years, mean (±SD)	58.4 (7.2)	60.2 (6.3)	62.2 (4.1)	43.9 (10.1)	<0.001
Age group (in years):					<0.001
18–40	12.6%	8.8%	*	48.4%
41–60	34.3%	34.7%	40.3%	21.4%
61–80	51%	54%	58.8%	27.8%
>80	2.1%	2.5%	0%	2.4%
Race:					<0.001
White	73.4%	75.2%	72.3%	62%
Black	6.1%	5.4%	14.3%	5%
Hispanic	10.7%	9%	7.1%	24.8%
Others^a	9.8%	10.3%	6.3%	8.3%
Female	41%	40.4%	35.3%	42.1%	0.468
Quarter:					0.111
Quarter 1 (January-March)	21.2%	21.1%	17.7%	25.4%
Quarter 2 (April-June)	23.2%	23.6%	20.2%	23.8%
Quarter 3 (July-September)	25.9%	26.2%	34.5%	16.7%
Quarter 4 (October-December)	29.7%	29%	27.7%	34.1%
Median household income:					0.590
Quartile 1 (poorest)	17%	17.2%	12.9%	20.2%
Quartile 2	20.7%	20.8%	18.1%	24.2%
Quartile 3	28.3%	28.3%	30.2%	24.2%
Quartile 4 (wealthiest)	34%	33.7%	38.8%	31.5%
Primary expected payer:					<0.001
Medicare	34.8%	35.2%	42%	26.4%
Medicaid	8%	6.8%	4.2%	20%
Private Insurance	51%	53.1%	42.9%	48%
Self-pay & other^b	6.2%	4.9%	10.9%	5.6%
Admitted to teaching hospital	99.4%	99.4%	98.3%	100%	0.524
Hospital bed size:					0.096
Small	13.8%	12.3%	13.5%	19.8%
Medium	13%	12.9%	7.6%	19.1%
Large	73.2%	74.8%	79%	61.1%
Region of Hospital:					<0.001
Northeast	27.7%	26.3%	42%	21.4%
Midwest	22.5%	25.5%	15.1%	15.1%
South	27%	27.5%	21.9%	24.6%
West	22.9%	20.8%	21%	38.9%
Charlson comorbidity index:					<0.001
2-3	76.6%	77.5%	84.9%	87.3%
>3	23%	22.5%	15.1%	12.7%
Comorbidities:
Cerebrovascular disease	3.6%	4.1%	*	3.2%	0.192
Coronary artery disease	7.4%	8%	9.2%	5.6%	0.500
Diabetes mellitus	13%	13.9%	10.9%	11.1%	0.547
Dyslipidaemia	21.7%	24.5%	17.7%	12.7%	0.011
Hypertension	39%	39%	49.6%	28.6%	0.003
Obesity	6.7%	6.8%	5.9%	8.7%	0.657
Valvular heart disease	2.1%	2.1%	4.2%	*	0.169
Venous thromboembolism^c	13%	14.4%	10.1%	8.7%	0.102
Complications:
Acute kidney injury	15%	15.2%	17.7%	13.5%	0.635
Acute respiratory failure	7.1%	6.7%	5%	10.3%	0.274
Fever	53.9%	57.1%	52.9%	46%	0.065
Neutropenia	38.3%	38.5%	35.3%	39.7%	0.703
Sepsis or infection	39.5%	40.9%	30.3%	46.8%	0.029
Procedure:
Invasive mechanical ventilation	4.9%	5%	3.4%	6.4%	0.568
Non-invasive ventilation	2.1%	2.4%	0%	2.4%	0.257
Length of stay (in days):					<0.001
≤10	21%	22.4%	6.7%	11.1%
11–20	50.7%	51.3%	74.8%	37.3%
≥21	28.3%	26.3%	18.5%	51.6%
Disposition of Patient:					0.185
Routine	79.2%	77.3%	88%	80.2%
Transfer to short-term hospital	0.7%	0.8%	0%	0%
Transfer to a facility^d	6.5%	7.7%	1.7%	4.1%
Home-health care	13.6%	14.1%	10.3%	15.7%
Left against medical advice	*	*	0%	0%
Outcomes:
All-cause-inpatient mortality	3.5%	3.6%	1.7%	4%	0.538
Length of stay in days, mean (±SD)	19.3 (7.5)	19.1 (7.7)	18.3 (5.6)	24.3 (7.6)	0.002
Total hospital charges in US dollars, mean (±SD)	$929,232 (512,098.3)	$1,111,451 (524,191.8)	$227,843.4 (20,9759.6)	$762,745 (493,894.3)	0.001
Total hospital costs in US dollars, mean (±SD)	$239,855.8 (106,577.5)	$286,741.5 (105,726.3)	$60,484.1 (51,782.2)	$191,145.3 (93,874.8)	<0.001

^aIncludes Asian or Pacific Islanders, Native Americans, and others.

^bIncludes no charge, worker's compensation, CHAMPUS, CHAMPVA, Title V, and other government programs.

^cIncludes both pulmonary embolism and deep vein thrombosis.

^dIncludes Skilled Nursing Facility (SNF), Intermediate Care Facility (ICF), another type of facility.

*Small numbers not reported due to database policy.

Baseline Characteristics of CAR-T Cell Therapy Admissions with and without Acute Respiratory Failure

Out of the 5545 admissions identified, 395 (7.1%) developed ARF, and we found no difference in the rate of ARF development among admissions with non-Hodgkin's Lymphoma, Multiple Myeloma, and Leukemia that underwent CAR-T therapy (Table 2). Age at admission, race, or gender was also not statistically different between admissions complicated by respiratory failure and those without respiratory failure. However, patients who developed acute respiratory failure were more likely to have cerebrovascular disease and venous thromboembolism as comorbidities (P < 0.05). The annual CAR-T cell therapy patients who developed ARF from 2017 to 2020, along with the corresponding mortality rates for each year are depicted in Figure 1. To examine the effect of the year of CAR-T Cell Therapy as a predictor of outcome, we calculated the adjusted odds ratio (aOR) for overall mortality and mortality from ARF using the year 2018 as a reference. The aOR for overall mortality and mortality from ARF for 2019 were 0.61 (CI 0.281-1.314) and 1.01 (CI 0.302- 3.386, respectively). For the year 2020, the aOR were 0.77 (CI 0.386-1.527) and 1.13 (CI 0.308-4.166, respectively). These differences were not significant.

Table 2.

Baseline Characteristics of CAR-T Cell Therapy Admissions With and Without Acute Respiratory Failure.

Variable	CAR-T cell therapy admission without Acute Respiratory Failure (N = 5150)	CAR-T cell therapy admission with Acute Respiratory Failure (N = 395)	P value
Cancer:
Non-Hodgkin's lymphoma	74.7%	73.4%	0.810
Multiple myeloma	11%	7.6%	0.366
Leukemia	11%	16.5%	0.176
Age at admission in years, mean (±SD)	58.4 (7.1)	57.7 (7.7)	0.656
Age group (in years):			0.669
18–40	12.3%	16.5%
41–60	34.6%	30.4%
61–80	51.1%	50.6%
>80	2%	*
Race:			0.481
White	73.5%	72.7%
Black	6.2%	5.2%
Hispanic	10.9%	7.8%
Others^a	9.4%	14.3%
Female	41.7%	32.9%	0.147
Quarter:			0.424
Quarter 1 (January-March)	21.4%	19%
Quarter 2 (April-June)	23.3%	21.5%
Quarter 3 (July-September)	25.3%	34.2%
Quarter 4 (October-December)	30%	25.3%
Median household income:			0.097
Quartile 1 (poorest)	16.4%	25.4%
Quartile 2	21.1%	15.5%
Quartile 3	28.9%	21.1%
Quartile 4 (wealthiest)	33.7%	38%
Primary expected payer:			0.480
Medicare	35.2%	29.1%
Medicaid	7.8%	10.1%
Private Insurance	51%	51.9%
Self-pay & other^b	6%	8.9%
Admitted to teaching hospital	99.4%	98.7%	<0.001
Hospital bed size:			0.834
Small	13.9%	12.7%
Medium	12.8%	15.2%
Large	73.3%	72.2%
Region of Hospital:			0.691
Northeast	28%	24.1%
Midwest	22.2%	25.3%
South	26.7%	30.4%
West	23.1%	20.3%
Charlson comorbidity index:			<0.001
0-1	0.5%	0%
2-3	78.1%	57%
>3	21.5%	43%
Comorbidities:
Cerebrovascular disease	2.8%	13.9%	<0.001
Coronary artery disease	7.3%	8.9%	0.665
Diabetes mellitus	12.9%	13.9%	0.807
Dyslipidaemia	21.8%	21.5%	0.964
Hypertension	38.2%	49.4%	0.036
Obesity	6.4%	10.1%	0.200
Valvular heart disease	2%	*	0.765
Venous thromboembolism^c	11.8%	29.1%	<0.001
Complications:
Acute kidney injury	12%	53.2%	<0.001
Fever	55.3%	35.4%	<0.001
Neutropenia	38.5%	36.7%	0.747
Sepsis or infection	36.6%	77.2%	<0.001
Procedure:
Invasive mechanical ventilation	0.9%	57%	<0.001
Non-invasive ventilation	1.1%	15.2%	<0.001
Length of stay (in days):			<0.001
≤10	22.5%	1.3%
11–20	52.6%	25.3%
≥21	24.9%	73.4%
Disposition of Patient:			<0.001
Routine	80.9%	45.3%
Transfer to short-term hospital	0.3%	7.6%
Transfer to a facility ^d	5.4%	26.4%
Home-health care	13.3%	20.8%
Left against medical advice	0.1%	0%
Outcomes:
All-cause-inpatient mortality	1.3%	32.9%	<0.001
Length of stay in days, mean (±SD)	17.9 (6.4)	37.5 (12.8)	<0.001
Total hospital charges in US dollars, mean (±SD)	$903,250.2 (508,989.6)	$1,273,745 (522,511.9)	0.002
Total hospital costs in US dollars, mean (±SD)	$232,008.1 (103,916.2)	$343,913.8 (126,212.7)	<0.001

^aIncludes Asian or Pacific Islanders, Native Americans, and others.

^bIncludes no charge, worker's compensation, CHAMPUS, CHAMPVA, Title V, and other government programs.

^cIncludes both pulmonary embolism and deep vein thrombosis.

^dIncludes Skilled Nursing Facility (SNF), Intermediate Care Facility (ICF), another type of facility.

*Small numbers not reported due to database policy.

The most common complications accompanying CAR-T admissions with acute respiratory failure were sepsis (77.2%), acute renal failure (53.2%), and fever (35.4%), which were more prevalent compared to admissions without respiratory failure (P < 0.05). Among the 395 CAR-T admissions with acute respiratory failure, 60 (15.2%) required non-invasive ventilation, and 225 (57.0%) required support with mechanical ventilation at some point during the admission. The remaining 110 patients (28%) did not require mechanical ventilation or non-invasive ventilation. Data on the type of oxygen supplementation or FIO2 are not available in this group of patients.

The all-cause in-hospital mortality for admissions complicated by ARF was higher than the admissions who did not develop ARF (32.9% vs 1.3%, P < 0.001). Disposition also differed significantly, with acute respiratory failure admissions more likely to be discharged to a facility (26.4% vs 5.4%) or require home healthcare (20.8% vs 13.3%) (P < 0.001). Those who developed acute respiratory failure had a statistically higher mean length of stay (37.5 vs 17.9 days, P < 0.001) and higher mean overall hospitalization cost ($343,913 vs $232,008, P < 0.001) compared to those without respiratory failure.

Outcomes of Acute Respiratory Failure in CAR-T Cell Therapy Admissions with and without Invasive Mechanical Ventilation

Of the 395 admissions who developed ARF, 225 required IMV. These represented 4.9% of the overall admissions for CART therapy and 57% of those who developed ARF. ARF admissions requiring IMV had higher mortality than those not requiring IMV (48.9% vs 11.8%, P = 0.001). The ARF cohort requiring IMV had higher total hospital costs compared to the ARF cohort not requiring IMV ($398,994.7 vs $270,472.6, P = 0.02) (Table 3).

Table 3.

Outcomes of CAR-T Cell Therapy Admissions With Acute Respiratory Failure comparing those who required IMV to those who did not.

Variable	CAR-T cell therapy admissions with Acute Respiratory Failure and without Invasive Mechanical Ventilation (N = 170)	CAR-T cell therapy admissions with Acute Respiratory Failure and with Invasive Mechanical Ventilation (N = 225)	P value
All-cause-inpatient mortality	11.8%	48.9%	0.001
Length of stay in days, mean (±SD)	31.7 (8.7)	41.9 (13.1)	0.055
Total hospital charges in US dollars, mean (±SD)	$1,029,687 (376,849.6)	$1,456,788 (523,101.7)	0.063
Total hospital costs in US dollars, mean (±SD)	$270,472.6 (95,515.1)	$398,994.7 (121,761.3)	0.020

Discussion

To our knowledge, this is the largest and only database study to date that characterizes CAR-T admissions, with a specific focus on admissions complicated by ARF. The all-cause mortality reported in our large database study was 3.5% for all CAR-T admissions, with the most frequent complications being sepsis, neutropenia, and fever. We identified that ARF was present in 7.1% of all CAR-T cell admissions, with a large number of admissions complicated by ARF (72.2%) requiring support with either non-invasive ventilation or invasive mechanical ventilation. We did not identify a difference in the incidence of ARF or the need for respiratory support among the three subgroups of hematological malignancies being treated by CAR-T therapy. Of note, admissions that developed ARF had significantly higher all-cause mortality (32.9%) when compared to admissions that did not (1.3%), suggesting that ARF is a harbinger of poor outcomes among CAR-T admissions. In those with ARF, the need for IMV was associated with significantly higher mortality compared to those who did not (48.9% vs 11.8%, respectively). Sepsis, acute renal failure, and fever were the most common complications of CAR-T admissions with ARF.

The outcomes of CAR-T therapy recipients have been the subject of a few observational studies and a recent meta-analysis.^2-4 One observational study of 942 CAR-T cell patients (CARTTAS) identified 27.5% of recipients (241 cases) requiring ICU admission. ARF was the reason for admission to the ICU in 10% of these cases.² Of all cases requiring ICU-level care, 5% required support with high-flow nasal oxygen, and 7% required invasive mechanical ventilation. In a study conducted by Gutierrez et al, which specifically examined 105 individuals admitted to the ICU for CRS or ICANS, it was found that 1.9% of admissions necessitated respiratory support with NIV, 8.6% required high-flow nasal oxygen, and 10.5% required invasive mechanical ventilation.³ Hospital mortality in this study was 15.2%, with the majority of deaths coming from disease progression or sepsis. A very recent meta-analysis including 4 studies of CAR-T recipients reported that of patients admitted to ICU, 10% had ARF.⁴ Among all ICU admissions, 18% required support with invasive mechanical ventilation at some point.⁴ Our study provides more specific findings related to those who had a diagnosis of ARF from a large in-hospital database, showing the incidence to be close to previously reported results (7.1%), with significantly higher mortality (32.9%), especially those who required IMV (48.9%).

The etiology of ARF following CAR-T cell therapy was not identified in this study. However, few reports have suggested that this complication could be related to cytokine release syndrome (CRS).⁶ CRS is characterized by the abrupt release of pro-inflammatory cytokines following CAR-T cell infusion and leading to a clinical syndrome ranging from mild flu-like symptoms to severe multi-organ dysfunction.^7,8 Isolated CRS is present in 34% of CAR-T cell therapy patients admitted to the ICU, and in addition, 26% combined with ICANS. Hypoxemia and respiratory failure are important clinical manifestations of CRS, with hypoxemia requiring support FiO2 > 40% discriminating between grade 2 and 3 CRS and the need for mechanical ventilation raising the grade to 4..⁹ The etiology of hypoxic respiratory failure in CRS is linked to the release of multiple cytokines that induce capillary leak, which can progress to non-cardiogenic pulmonary edema in advanced cases^6,9 The mainstay of management in high-grade CRS, after appropriate supportive measures with supplemental oxygen, and non-invasive ventilation, includes suppression of cytokines with the anti-IL-6 medication tocilizumab as well as systemic glucocorticoids.^10-11 Although hypoxic respiratory failure from CRS is well described in the literature and is likely the most common cause of ARF, the extent to which other etiologies are responsible for ARF is not known. Other potential causes of ARF following CAR-T cell therapy include encephalopathy related to ICANS, acute pneumonia, sepsis, aspiration pneumonitis, and pulmonary embolism. Further studies are needed to study the etiologies of ARF following this therapy.

The current study provides valuable information on the incidence and outcome of CAR-T cell patients with ARF. However, this analysis has several limitations. A notable one is the absence of specific information on the etiology of ARF or whether ARF served as a primary complication or was part of a broader multi-organ system failure. This remains an important clinical question that requires further study. There is no data on the investigations and treatment that these patients received. In addition, it is important to recognize the unique structure of the NIS database, where individual patients remain unidentifiable, and each recorded entry represents a discrete hospital admission rather than a continuous patient profile.¹² This inherent design feature limits longitudinal tracking of individuals across multiple hospitalizations, potentially obscuring aspects of disease progression and treatment trajectories. Due to the structure of the NIS database, we had to merge admission data from 2017 through 2022 for our analysis. However, in this structure we were unable to assess whether the year of admission and CART therapy independently contributed to complications such as ARF. We also have no data on the type of oxygen supplementation in the group of patients who did not require mechanical ventilation or noninvasive ventilation. While utilizing a national-level database in our study, it's essential to interpret results with caution due to potential misclassification bias from the administrative nature of the database. Additionally, the reliance on administrative data introduces questions regarding accuracy and completeness, with coding errors and variations in coding practices across healthcare facilities introducing a measure of variation in results. As such, we should exercise caution in generalizing findings from database studies and consider supplementary methodologies, such as prospective studies or randomized controlled trials, to enhance the robustness of conclusions drawn from NIS data.

Conclusion

CAR-T cell therapy is increasingly acknowledged as a treatment for various malignancies. A substantial number of these patients may necessitate ICU support for ARF and other critical conditions. This analysis indicates a high mortality rate associated with the development of ARF in these patients. Effective management requires close collaboration among pulmonologists, intensivists, hematologists/oncologists, and other specialists. Urgent research is needed to provide guidance for the comprehensive management of these patients.

Supplemental Material

sj-docx-1-jic-10.1177_08850666241253537 - Supplemental material for Epidemiology and Outcomes of Hospitalized Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Patients Who Developed Acute Respiratory Failure

Supplemental material, sj-docx-1-jic-10.1177_08850666241253537 for Epidemiology and Outcomes of Hospitalized Chimeric Antigen Receptor T-Cell (CAR-T) Therapy Patients Who Developed Acute Respiratory Failure by Daniel Kurtz, Aditya Sharma, Aditi Sharma and Ayman O. Soubani in Journal of Intensive Care Medicine

Footnotes

Financial Disclosure

None reported.

Declaration of Conflicting Interests

The authors whose names are listed immediately below certify that they have NO affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

ORCID iD

Ayman O. Soubani

Supplemental Material

Supplemental material for this article is available online.

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