Grant Number:	5R03CA259489-03 Interpret this number
Primary Investigator:	Barata, Anna
Organization:	Massachusetts General Hospital
Project Title:	Development and Validation of a Patient-Reported Measure Assessing Chimeric Antigen Receptor (CAR) T-Cell Therapy-Related Side Effects
Fiscal Year:	2023

PROJECT SUMMARY Chimeric antigen receptor (CAR) T-cell therapy is transforming care for adult patients with hematological malignancies who have otherwise poor prognoses. Up to 40% of patients with large B cell lymphoma (LBCL) can expect to survive at least two years after infusion of CAR T-cell therapy, in contrast to a mean overall survival of 6 months before the advent of CAR T-cell therapy. Moreover, many more trials are underway to evaluate CAR T-cell therapy for other hematologic and solid malignancies. As a result, there is an increasing population of survivors who experience the unique side effects associated with CAR T-cell therapy such as cytokine release syndrome (CRS) and neurotoxicity. Data on toxicities of CAR T-cell therapy come almost exclusively from physician-rated adverse events (AEs) on clinical trials. In contrast, patient-reported outcomes (PROs) provide important information from the patient’s perspective that is complementary to AEs. The FDA defines PROs as: 1) symptoms of disease, 2) side effects of treatment, and 3) quality of life. Although there are well-validated measures of symptoms of disease (#1) and quality of life (#3), there are no validated measures that capture the unique side effects of CAR T-cell therapy (#2). Lack of such a measure limits attempts to conduct research and patient education about this novel therapy. This study will develop and validate a new measure assessing patient- reported side effects of CAR T-cell therapy. Measure development will follow FDA measure development guidelines and be available in English and Spanish. In Aim 1, qualitative interviews will be conducted with 20 CAR T-cell recipients, 20 informal family caregivers, and 20 medical providers with expertise in CAR T-cell therapy. Patients and caregivers will be sampled across the survivorship trajectory to ensure adequate representation of a variety of experiences since CAR T-cell therapy. Qualitative interviews will identify patient- reported side effects that are common, severe, distressing, and diagnostically important over the course of CAR T-cell therapy, recovery and survivorship. Side effects will be mapped on to the Functional Assessment of Chronic Illness Therapy (FACIT) item library of 700 unique PRO items. New items will be written for side effects that do not have a corresponding FACIT item. In Aim 2, cognitive interviews with 20 additional patients will be conducted to ensure the readability, comprehensibility, and face validity of the item bank as well as generate additional items as needed. In Aim 3, convergent, divergent, and discriminant validity as well as reliability will be evaluated in a cross-sectional study assessing 150 CAR T-cell therapy patients at various times since treatment. The current project is highly innovative. From a research perspective, the measure will provide important data in observational, interventional, and therapeutic trials with CAR T-cell therapy recipients. From a clinical perspective, the measure will lead to a better detection of patient-reported side effects to improve supportive care for this population.





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