An Examination of Side-Effects in CAR-T Versus Other Therapies in Patients with Relapsed Lymphoma and Chronic Lymphocytic Leukemia - an Analysis from the Lymphoma Coalition's 2024 Global Patient Survey on Lymphomas & CLL
Authors: Kalloger Steve E , Watson Amanda , Sajkowski Shawn , Perry Kathryn , Bolanos Natacha , Warwick Lorna 
Published: December 2024

Introduction
The expansion of CAR-T continues to improve life expectancy for patients with various subtypes of lymphoma. In 2023, Lymphoma Coalition (LC) presented an analysis at ASH based on our 2022 Global Patient Survey on Lymphomas & CLL (GPS). Due to a paucity of data, we were only able to examine aggregate side effects to draw inferences regarding increased incidence of side-effects associated with different therapies. In that study, CAR-T showed significantly higher odds of having more side-effects. In this follow-up study, we continue to focus on CAR-T side effects, but we are using data from the LC 2024 GPS with a greater number of subtypes and an increased number of respondents. Our goal is to increase the granularity of our study to directly address the incidence of individual side-effects in those receiving CAR-T versus other therapies.
Methods
Patients with relapsed lymphomas who responded to the LC 2024 GPS were asked what treatments (N = 22) they had received and which side-effects they had experienced (N = 35). Univariable contingency analysis was used to examine differences in side-effect incidence for those receiving CAR-T versus any other treatment. Differences were assessed with odds ratios, 95% confidence intervals and p-values from the likelihood chi-square statistic as appropriate.
Results
Overall, 1940 patients met the eligibility criteria for our study and had a median age of 65 [18-91] years. Females comprised 56% of the respondents. CART-T therapy was used in 169 patients (5.3%). The study sample consists of 19 subtypes. The 5 most prevalent subtypes in the sample included chronic lymphocytic leukemia, follicular lymphoma, Waldenstrom's macroglobulinemia, diffuse large B-cell lymphoma and Hodgkin lymphoma and accounted for 80% of the study sample. Significantly increased incidence of side-effects associated with CAR-T included: cytokine release syndrome OR = 45.7 [28.3 - 73.6]; neurological effects OR = 6.0 [3.9 - 9.3]; tumor lysis syndrome OR = 4.3 [2.0 - 9.4]; blood clots OR = 2.9 [1.8 - 4.6]; pain OR = 2.3 [1.6 - 3.2]; muscle weakness OR = 2.3 [1.64 - 3.1]; anemia OR = 2.2 [1.6 - 3.0]; diarrhea OR = 2.2 [1.6 - 3.0]; respiratory problems OR = 2.1 [1.5 - 3.0]; hair loss OR = 2.1 [1.5 - 2.9]; infertility OR = 2.0 [1.2 - 3.4]; liver problems 1.9 [1.1 - 3.1]; headaches OR = 1.9 [1.1 - 3.1]; loss of appetite OR = 1.7 [1.2 - 2.4]; nausea and vomiting OR = 1.7 [1.2 - 2.4]; infections OR = 1.7 [1.2 - 2.3]; changes in taste and smell OR = 1.6 [1.2 - 2.3]; hearing changes/loss OR = 1.6 [1.1 - 2.5]; constipation OR = 1.6 [1.2 -2.2]; fatigue OR = 1.6 [1.1 - 2.3]; loss of memory OR = 1.5 [1.1 - 2.2]. Borderline significance was found for: sexual and intimacy problems OR = 1.5 [1.0 - 2.3] and changes in sleep patterns OR = 1.5 [1.1 - 2.1]. The remaining side-effects examined failed to demonstrate significant differences with regard to the use of CAR-T. The above analysis represents that approximately 65% of the side effects examined in our survey had significantly increased odds of being associated with CAR-T relative to those who received other treatments.
Conclusions
Our analysis suggests that patients who receive CAR-T have increased odds of experiencing a wide variety of side effects. While it can be argued these toxicities may be attributable to other therapies experienced prior to or post CAR-T, the results indicate that these patients are likely to have a greater incidence of side effects. We also recognize that these are patient reported outcomes and that recall bias may influence these results. However, these results essentially replicate the findings from our 2022 data which yields a degree of external validity. We plan to determine which of these side effects track together and work toward building a predictive algorithm that will aid in the early identification of patients treated with CAR T who may be predisposed to side effects. We feel that this will enable care teams to provide optimal supportive care to those at increased risk and thereby improve the recovery and rehabilitation of this vulnerable population.