An Examination of Aggregate Side-Effects Mapped to Therapies Experienced by Patients with Relapsed Large B-Cell Lymphomas
An Analysis from the Lymphoma Coalition’s 2022 Global Patient Survey
Authors:
S. E. Kalloger¹, S. Sajkowski¹, A. Watson¹, and L. Warwick²
¹ Department of Research and Information, Lymphoma Coalition, Mississauga, ON, Canada
² Management, Lymphoma Coalition, Mississauga, ON, Canada
Introduction
The identification of side-effects associated with a particular therapy relies on univariable assessments of incidence across treatment arms. While this approach serves to set the groundwork for the establishment of causation, it is suboptimal when the incidence is small or when novel therapeutics with limited deployment are being examined.
In this study, we used a multivariate approach to aggregate multiple symptoms in order to segment our sample into those who had differing degrees of side-effect incidence. We used the resultant strata to examine the use of various therapies.
Method
- Patients with relapsed large B-cell lymphomas who responded to the Lymphoma Coalition’s 2022 Global Patient Survey (N=215) were asked if they had ever been treated with a particular treatment (N=20) and what side effects (N=32) they had ever experienced.
- Unsupervised hierarchical clustering utilizing Ward’s algorithm was used to aggregate the incidence of side-effects (N=32).
- Resultant strata from the hierarchical clustering procedure were subjected to contingency analysis with the use of 20 treatments.
- Differences were assessed with odds ratios, 95% confidence intervals, and p-values from the likelihood chi-square statistic as appropriate.
Results
The total number of respondents meeting the criteria for inclusion in this study was 215. The median age of respondents was 58, ranging from 23–85 years. Females comprised 55% of the study sample.
A hierarchical clustering analysis was used to segment the study sample at the first branch, yielding two clusters:
- Cluster 1: N = 76
- Cluster 2: N = 139
The rationale for selecting two clusters was based upon an obvious difference in side-effect incidence.
- Cluster 1: 1,570 cumulative side-effects, incidence rate = 11.3 per patient
- Cluster 2: 272 cumulative side-effects, incidence rate = 3.6 per patient
Key Findings
- Significantly increased odds of CAR T (p=0.001), steroids (p=0.05), and radiation therapy (p=0.01) were found in Cluster 1 relative to Cluster 2.
- No significant change in odds ratio was detected for the other 17 treatments.
Conclusions
The results suggest that there is an association of increased side-effects for those receiving CAR-T. Additionally, radiotherapy was also found to be primarily more used in those with more side-effects.
The fact that steroid use was also increased in this cluster of patients makes sense since that is routine prophylactic management for patients experiencing substantial side-effects.
From the heat map, we can infer two things:
- There are groups of at least five effects that tend to cluster together, which may reflect treatment heterogeneity.
- About one-third of patients experience very few side-effects, supporting the idea of patient heterogeneity.
There are some limitations to this work, including the use of patient reported outcomes and the fact that we were unable to explicitly map the treatment course of every individual patient.
However, the study does support the idea that the diversity of the side-effect profile for CAR-T may extend beyond the traditional phenomenon of cytokine release syndrome, blood, and neurological effects.
We suspect that as the use of CAR-T expands, additional side-effects will become apparent. Future studies should focus on identifying individuals who are likely to experience significant side-effects and mapping treatment strategies to the appropriate patients.
Acknowledgements
The Lymphoma Coalition (LC) would like to acknowledge and thank every patient and caregiver who took the time to fill out the 2022 survey. Through sharing your experiences, you have allowed us to amplify your voices, creating the potential for change.
Contact Information
For further details on the LC 2022 Global Patient Survey, please visit:
🔗 https://lymphomacoalition.org/global-patient-survey
Please direct any queries to the research department at Lymphoma Coalition:
📧 steve@lymphomacoalition.org
Summary
This study analyzed data from 215 patients with relapsed large B-cell lymphoma who responded to the Lymphoma Coalition’s 2022 Global Patient Survey. Researchers examined the relationship between therapies and the aggregate incidence of side-effects using a clustering approach.
- Method: Patients reported treatments received and side-effects experienced. Using unsupervised hierarchical clustering, two patient groups were identified based on side-effect burden.
- Findings:
- Cluster 1 (N=76): Higher side-effect incidence (11.3 per patient).
- Cluster 2 (N=139): Lower side-effect incidence (3.6 per patient).
- Patients in Cluster 1 had significantly higher odds of having received CAR-T, steroids, and radiation therapy.
- No significant differences were found for 17 other treatments.
- Conclusions:
- CAR-T therapy is strongly associated with higher side-effect burden, which may extend beyond known issues like cytokine release syndrome and neurological effects.
- Results highlight patient heterogeneity, with some experiencing few side-effects and others many.
- Future research should focus on identifying patients at risk for significant side-effects to guide personalized treatment strategies.