Grant Number:	5R01CA244328-03 Interpret this number
Primary Investigator:	Jim, Heather
Organization:	H. Lee Moffitt Cancer Ctr & Res Inst
Project Title:	Neurocognitive and Patient-Reported Outcomes After Chimeric Antigen Receptor T-Cell Therapy: a Controlled Comparison
Fiscal Year:	2024

PROJECT SUMMARY There is widespread excitement about chimeric antigen receptor (CAR) T-cell therapy, which causes complete disease response in 40%-54% of adults with relapsed/refractory large B-cell lymphoma (LBCL), compared to a response rate of 7% to chemotherapy prior to the advent of CAR T-cell therapy. For the first time, long-term disease-free survival is possible for patients with advanced LBCL. CAR T-cell therapy causes a unique profile of adverse events, including cytokine release syndrome (CRS) and neurologic events, which may be risk factors for cancer-associated cognitive decline (CACD). However, little is known about neurocognition and patient- reported outcomes (PROs; e.g., symptoms, quality of life or QOL) in CAR T-cell therapy patients. The goal of the current study is to investigate longitudinal changes in PROs and CACD, outcomes that are highly relevant to survivorship, in the first year after CAR T-cell therapy. We will recruit 204 LBCL patients treated with CAR T-cell therapy and 102 age-, sex-, and education-matched individuals without cancer. Participants will be assessed at pre-CAR T-cell therapy baseline and 3 and 12 months later to capture acute and longer-term outcomes. At each time point, participants will complete internet-based neuropsychological testing, validated PRO questionnaires, and 7-day smartphone-based ecological momentary assessment (EMA) of cognition and self-reported risk factors for CACD (i.e., fatigue, depression, pain, stress). Actigraphy during EMA periods will be used to objectively measure sleep, physical activity, and sedentary behavior as behavioral factors for QOL and CACD. Blood will be collected and banked at each assessment for future examination of biological mechanisms (e.g., inflammation, accelerated cellular aging). Data will be used to address the following aims: 1) to examine baseline differences and longitudinal changes in patient-reported outcomes and cognition in CAR T-cell therapy recipients and controls, 2) to identify demographic, contextual, and clinical risk factors that are associated with worse cognition in CAR T-cell therapy recipients compared to controls, and 3) to determine behavioral protective factors associated with better cognition among CAR T-cell therapy recipients and controls. This research will be highly impactful, providing the data needed to educate patients and their families about CAR T-cell therapy in collaboration with the Leukemia and Lymphoma Society. Analyses focused on risk and protective factors will provide insights into potential targets of intervention to improve QOL and CACD in this novel cancer survivor population.