Study Evaluates Impact of AE Severity on Health State Utility for CAR T Treatment in LBCL

With multiple chimeric antigen receptor (CAR) T-cell therapies available, understanding the health state utilities associated with toxicities of treatment can provide a way to compare the value of these treatments. As may be expected, more severe adverse events (AEs) are associated with greater disutility, or utility decrease, in large B-cell lymphoma (LBCL), according to a study published in PharmacoEconomics – Open.

Two important toxicities associated with CAR T-cell therapies are cytokine release syndrome (CRS) and neurological events (NEs). Both can become severe and require intensive treatments and rates of severe CRS have ranged from 2% to 22% in clinical trials for various CAR T-cell therapies and rates of NEs have ranged from 10% to 28%.

“As more CAR T-cell treatments are introduced, cost-utility analyses (CUAs) can be used to examine their value and inform decision making on healthcare resource allocation,” the authors explained. Health state utilities, which are valued to 0 (dead) and 1 (full health), are factored into CUAs to calculate quality-adjusted life-years. “Because the CAR T-cell therapies differ in the rates of CRS and NEs, a CUA comparing these treatments should incorporate utility differences associated with these [AEs].”

The researchers estimated health state utilities associated with CAR T-cell therapy toxicities using health state vignettes based on literature review, AE reports from a trial, and clinician input.

A total of 6 health states were developed describing a year in the life of a patient with LBCL who experienced various AEs after CAR T-cell therapy and prior to recovery.

• Health state A: no AEs
• Health state B: grade 1 CRS
• Health state C: grade 2 CRS
• Health state D: grade 3/4 CRS
• Health state E: grade 1/2 NE
• Health state F: grade 3/4 NE

The clinician reports of the typical patient experience of each AE and the published literature of AE reports from a clinical trial were used to maximize the representativeness of these health state vignettes.

A pilot study tested the time trade-off (TTO) methods with a sample of the general population. The Eq-5D-5L, which comprises 5 dimensions to describe and value health, was administered to characterize the health status of the sample population.

A total of 366 potential participants were reached but only 218 interviews were included in the analysis, with 113 patients from London and 105 patients from Edinburgh. While age, sex, marital status, and education level were similar between the 2 groups, the Edinburgh group had a higher rate of White patients and a lower rate of patients employed full time.

Depression, anxiety, diabetes, arthritis, and hypertension were the most common medical and mental health conditions, but 43.6% reported no health conditions. None of the participants reported having a diagnosis of LBCL, but 9 said they knew someone with LBCL. Another 5 participants were diagnosed with another type of lymphoma and 57 knew someone with another type of lymphoma

The results of the 5Q-5D-5L found few issues with mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.

In the study, the participants ranked the health states in order of preference with health state A (no AEs) ranked as most preferable by all participants and health state D (grade 3/4 CRS) and health state D (grade 3/4 NE) ranked as least preferable. Mean rankings from most preferred to least were A, B, E, C, F, and D. Mean utility scores ranked from most preferred to least were A (0.73), B (0.71), E (0.69), C (0.68), F (0.55), and D (0.50).

“Grade 3/4 AEs (described in health states D and F) had substantially larger disutilities than the less severe AEs (described in health states B, C, and E),” the authors wrote. These are life-threatening events that require longer hospitalization and possibly intensive treatments such as mechanical ventilation.

Participants were most willing to trade time in perfect health to avoid living in health state D (89.0%), followed by F (86.7%), C and E (78.9%), B (75.2%) and A (72.0%). “Most participants perceived all health states as better than dead,” they noted.

The Edinburgh group has consistently lower utility scores for health states B through F, but there was no significant difference in the utility for health state A.

The limitation of this kind of study is that the scores represent the general population and not the experience of the actual patients.

“The rates and severity of the AEs represented in the health states can differ across the CAR T-cell treatments. By incorporating disutility of these AEs, CUAs can more accurately and comprehensively model the differences among available treatments for LBCL,” the authors concluded.

Reference

Howell TA, Matza LS, Jun MP, Garcia J, Powers A, Maloney DG. Health state utilities for adverse events associated with chimeric antigen receptor T-cell therapy in large B-cell lymphoma. Pharmacoecon Open. Published online February 7, 2022. doi:10.1007/s41669-021-00316-0