Real-world patient-reported symptomatic adverse events and concordance with physician assessments after CAR T-cell therapy in patients with aggressive B-cell lymphomas: a prospective study
Menée en Italie à partir de données en vie réelle portant sur 170 patients atteints d'un lymphome agressif à cellules B (âge médian : 61,1 ans ; durée médiane de suivi : 23,7 mois), cette étude prospective analyse les événements indésirables induits par une immunothérapie à base de lymphocytes CAR-T et auto-déclarés par les patients, puis évalue la concordance avec ceux rapportés par les médecins
Background: Chimeric antigen receptor (CAR) T cells have shown considerable promise in treating patients with haematological malignancies. We aimed to investigate short-term patient-reported symptomatic adverse events in patients with aggressive B-cell lymphomas treated with CAR T-cell therapy and compare them with those reported by their treating physicians. We also examined factors predicting overall short-term burden of therapy.
Methods: This was a prospective, observational, multicentre study enrolling patients across 13 centres in Italy. Eligible patients were aged 18 years and older with a confirmed diagnosis of aggressive B-cell lymphoma. All patients were scheduled to undergo CAR T-cell therapy with one of the following products: axicabtagene ciloleucel (axi-cel), tisagenlecleucel (tisa-cel), or brexucabtagene autoleucel (brexu-cel). The primary objective of this analysis was to assess the prevalence of short-term patient-reported symptomatic adverse events overall and by sex and age categories. The primary objective was evaluated on day 10 after infusion via the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE), which includes 19 items selected based on their clinical relevance, including: difficulty swallowing, decreased appetite, nausea, diarrhoea, swelling, hair loss, dizziness, concentration difficulty, memory difficulty, general pain, headache, muscle pain, joint pain, insomnia, fatigue, anxiety, discouragement, sadness, and chills. Prevalence of symptomatic adverse events was also assessed by type of CAR T-cell product. Additionally, the study was designed to allow a corresponding adverse event assessment via the CTCAE by treating haematologists for comparative analysis. Adverse events reported by physicians were matched with corresponding adverse events reported by patients. Furthermore, an overall symptom burden score was computed and used as outcome variable in multivariable analysis to examine factors predicting short-term burden of therapy, including sociodemographic and clinical data and pre-infusion patient-reported physical functioning by the EORTC QLQ-C30. The study is registered with ClinicalTrials.gov, NCT06026644, and is closed to accrual and follow-up is complete.
Findings: Between June 29, 2022, and Feb 26, 2024, 170 patients were included in the study. The median age of patients was 61·1 years (IQR 51·1–68·5) and the median follow-up was 23·7 months (17·7–24·6). 53 (31%) of 170 enrolled patients were female and 117 (69%) were male. Most patients were diagnosed with diffuse large B-cell lymphoma (118 [69%] patients), followed by mantle cell lymphoma (32 [19%] patients) and primary mediastinal large B-cell lymphoma (20 [12%] patients). 98 (58%) patients were infused with axi-cel, 39 (23%) with tisa-cel, and 32 (19%) with brexu-cel. 165 patients reached the day 10 timepoint, of whom 143 (87%) completed the corresponding PRO-CTCAE item list. We observed a prevalence (any grade) of more than 50% across 12 of the 19 symptomatic adverse events examined: fatigue (123 [87%] of 141 patients), decreased appetite (116 [83%] of 139 patients), insomnia (112 [79%] of 142 patients), chills (103 [73%] of 142 patients), diarrhoea (99 [70%] of 141 patients), sadness (81 [57%] of 141 patients), general pain (78 [55%] of 143 patients), dizziness (78 [55%] of 143 patients), joint pain (74 [52%] of 142 patients), muscle pain (73 [51%] of 143 patients), headache (73 [51%] of 143 patients), and impaired concentration (72 [51%] of 142 patients). Inspection of moderate to severe grades revealed that more than 30% of patients reported fatigue (78 [55%] of 141 patients), decreased appetite (74 [53%] of 139 patients), diarrhoea (63 [45%] of 141 patients), chills (49 [35%] of 142 patients), and insomnia (44 [31%] of 142 patients). Physicians frequently under-reported symptoms in their patients. For example, gastrointestinal symptoms were consistently under-reported, including difficulty swallowing (28 [78%] of 36 patients), decreased appetite (75 [77%] of 98 participants), nausea (43 [70%] of 61 participants), and diarrhoea (60 [71%] of 85 participants).
Interpretation: Our findings could assist clinicians in delivering more targeted and timely supportive care interventions and might inform patients about anticipated symptoms during the early post-CAR T-cell infusion period. Moreover, the observed discrepancies between patient-reported and clinician-reported symptoms suggest that more systematic use of patient-reported outcome measures might provide complementary insights beyond those captured through clinician assessment.
The Lancet Oncology , résumé, 2026