Factors Predicting Short-Term Symptom Burden in Patients with Aggressive B-Cell Lymphomas Treated with CAR T-Cell Therapy: A Real-World Study By the Gimema
Authors: Efficace Fabio , Bonifazi Francesca , Zinzani Pier Luigi , Cutini Ilaria , Chiappella Annalisa , Botto Barbara , Tisi Maria Chiara , Bramanti Stefania , Baldi Thomas , Tartaglia Francesca , Farina Mirko , Ragaini Simone , Gambella Massimiliano , Orciuolo Enrico , Martino Massimo , Martelli Maurizio , Cartoni Claudio , Corradini Paolo , Fazi Paola , Vignetti Marco , Di Rocco Alice 
Published: December 2024

Background
The development of chimeric antigen receptor (CAR) T-cell therapy has resulted in remarkable progress in the treatment of patients with aggressive B-cell lymphomas. However, very limited data exists on factors associated with short-term symptom burden and on adverse events (AE) profile.
Objective
The primary objective of this study was to investigate baseline factors predicting overall patient-reported short-term symptom burden (i.e., at day +10 after CAR T-cell infusion).
A secondary objective was to describe the prevalence of moderate to severe patient-reported AEs, by key socio-demographic and clinical characteristics.
Methods:
This was a multicenter prospective observational study including adult patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified, primary mediastinal large B-cell lymphoma (PMBCL), high grade B-cell lymphoma, and DLBCL transformed by indolent lymphoma and mantle cell lymphoma (MCL), scheduled to receive CAR T-cell therapy.
Patient-reported AEs were evaluated at day +10 after CAR T-cell infusion, using 19 items selected from the validated NCI PRO-CTCAE item library. These included: difficulty swallowing, decreased appetite, nausea, diarrhea, swelling, hair loss, dizziness, concentration, memory, general pain, headache, muscle pain, joint pain, insomnia, fatigue, anxious, discouraged, sad and chills. Each symptom was rated based on recommended standards, for example with regard to severity grading: 0=none, 1=mild, 2=moderate, 3=severe, 4= very severe. An overall symptom burden score was computed based on a previously developed composite grading algorithm for PRO-CTCAE items, with a higher score indicating a higher symptom burden. Univariable and multivariable linear regression analyses were performed to investigate several key factors, including baseline self-reported physical functioning (PF) by the EORTC QLQ-C30, predicting a higher symptom burden at day +10.
We also computed the percentage of patients reporting moderate to severe (≥ 2) AEs by age, sex, type of diagnosis, CAR T-cell product and baseline PF.
Results
Overall, 170 patients were enrolled between June 2022 and February 2024. At day +10, 143 (84%) patients were eligible for this analysis. Median age at study entry was 60.2 years and 59%, 24% and 17% were treated with axicabtagene ciloleucel, tisagenlecleucel and brexucabtagene autoleucel, respectively.
The following variables were considered in the starting univariable model for short-term symptom burden: age, sex, time from diagnosis to CAR T-cell infusion, ECOG performance status, Ann Arbor stage, CAR T-cell product, type of diagnosis, presence of comorbidity, disease status, systemic B symptoms, bulky disease, as well as baseline PF. The variables retained in the final multivariable model were baseline self-reported PF (10-point increase, β= -1.10, C.I. -1.90, -0.30, p=.009) and sex (female vs male, β= -3.20, C.I. -6.20, -0.12, p=.042).
A different AE profile was most frequently observed by baseline PF. Indeed, patients reporting better PF (above the median cut-off value of 86.67) had a lower prevalence of moderate to severe toxicities for fatigue (32% vs 67%, p&lt;.001), decreased appetite (34% vs 63%, p=.001), nausea (11% vs 27%, p=.029), general pain (6% vs 20%, p=.037), muscle pain (6% vs 20%, p=.037), joint pain (4% vs 18%, p=.025), insomnia (19% vs 37%, p=.032), memory (0% vs 9%, p=.030), sad (0% vs 24%, p&lt;.001), anxious (9% vs 24%, p=.025) and discouraged (4% vs 20%, p=.013).
Also, female patients reported higher moderate to severe grade (with respect to male) for: fatigue (74% vs 47%, p=.003), general pain (27% vs 10%, p=.009), muscle pain (25% vs 11%, p=.034), dizziness (25% vs 9%, p=.011), joint pain (23% vs 9%, p=.028) and memory (14% vs 3 %, p=.025). Differences in the patient-reported (moderate to severe) AEs profile by age, type of diagnosis and CAR T-cell product were less evident.
Conclusion:
Our findings suggest that inclusion of a baseline self-reported PF assessment, in the setting of CAR T-cell therapy, may facilitate identification of vulnerable patients most in need of special attention just after CAR T-cell infusion.