Patient-Reported and Neurocognitive Outcomes in Patients Treated with Axicabtagene Ciloleucel
Authors: Jim Heather S.L. , Hoogland Aasha I. , Collier Aaron , Booth-Jones Margaret , Jain Michael D. , Locke Frederick L. 
Published: October 2019

Abstract
Background: Axicabtagene ciloleucel (axi-cel) is a CD19 targeted chimeric antigen receptor (CAR) T-cell therapy that may induce durable responses in relapsed/refractory lymphoma patients whose survival prospects are otherwise poor. Recent FDA approval of axi-cel and other CAR T-cell therapies is expected to lead to a growing population of cancer survivors treated with these therapies. Little is known about patient-reported outcomes (PROs) such as symptomatology and quality of life (QOL) in these patients. The goal of the current observational study was to examine PROs and neurocognitive functioning in adult patients in the first 90 days after treatment with axi-cel.
Methods: Patients who were scheduled to undergo axi-cel therapy as part of a clinical trial or standard of care at Moffitt Cancer Center were recruited prior to conditioning chemotherapy. Patients completed items from the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) at enrollment and 14, 30, 60, and 90 days post-CART. A total of 20 symptoms were selected for inclusion based on clinician-rated toxicity of CART reported on clinical trials as well as symptoms likely to be of concern to cancer patients (e.g., fatigue, insomnia, diarrhea, constipation, nausea, decreased appetite). Patients also completed the Medical Outcomes Study Short Form 36 (SF-36) QOL measure at baseline and 90 days. Neurocognitive assessments were completed at baseline and 30 days using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Means, SDs, frequencies, and Wilcoxon signed rank tests were used to characterize outcomes and change over time.
Results: Participants were 29 patients (28% female; mean age=58, SD=13; 52% treated on an interventional trial). Participants were diagnosed with diffuse large B-cell lymphoma (76%), follicular lymphoma or transformed follicular lymphoma (10%), mediastinal large b cell lymphoma (3%), or other indications (11%). Of these, 11 completed neurocognitive testing at baseline and 30 days. Patient-reported symptoms spiked at 14 days post-CAR-T before returning to levels similar to baseline. The most common symptoms at 14 days post-CAR-T were decreased appetite (95% any severity, 48% moderate to severe), fatigue (95% any severity, 43% moderate to severe), and dry mouth (85% any severity, 38% moderate to severe). By 90 days post-CAR-T, the most common symptoms were fatigue (82% any severity), insomnia (55% any severity), and joint pain (45% any severity); no patients reported moderate to severe symptoms at this time. Non-significant improvements were observed in physical health QOL (mean increase=1.43; p=0.37) and mental health QOL (mean increase=2.66, p=0.07) from baseline to 90 days. Patients demonstrated non-significant declines in total RBANS percentile score from baseline to day 30 (mean decrease=-8.18, p=0.32). Updated results will be presented at the meeting.
Conclusions: This study is the first to our knowledge to report on both PROs and neurocognitive outcomes in patients treated with CAR T-cell therapy. Results indicate that moderate-to-severe patient-reported symptoms were transient following axi-cel, although a majority of patients reported ongoing, low-grade symptoms at 90 days post-treatment. Quality of life and neurocognition did not significantly change over time. These preliminary findings warrant larger future studies with longer follow-up to better understand changes in PROs and neurocognition in cancer survivors treated with CAR-T.

Disclosures
Jim: Janssen: Consultancy; RedHill Biopharma: Consultancy. Locke:Kite Pharma: Other: Scientific Advisor; Novartis Pharmaceuticals: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy.