Worsening Financial Toxicity Among Patients Receiving Chimeric Antigen Receptor t-Cell (CAR-T) Therapy: A Mixed Methods Longitudinal Study
Authors: Cusatis Rachel , Tan Irena , Piehowski Claire , Akinola Idayat , Crawford Emma , Craig Juliana , Thiengmany Aline , Frank Matthew J. , Miklos David B. , Shah Nirav N. , D'Souza Anita , Knight Jennifer M , Muffly Lori , Flynn Kathryn E , Sidana Surbhi 
Published: November 2021

Abstract
Introduction: CAR-T cell therapy is associated with extra-ordinary costs with estimates of as much as $1.5 million in some patients, including the high list-price for the CAR-T product, additional costs of inpatient stay, toxicity management and outpatient follow-up. As a result, CAR-T therapy may be associated with financial toxicity for patients due to high costs, as well as the financial strain of travel and/or temporary relocation. To date, there are no published studies assessing financial toxicity among CAR-T patients.
Methods: Adult patients with hematologic malignancies receiving CAR-T therapy (commercial and clinical trial products) were prospectively recruited from two academic centers to this longitudinal, mixed methods study evaluating financial toxicity in CAR-T recipients. Patients completed questionnaires and telephone interviews prior to CAR-T, 28 days (questionnaire only), 90 days, and 180 days after treatment. The questionnaire included the Comprehensive Score for Financial Toxicity (COST-FACIT), a validated questionnaire with 12 questions on financial stressors of cancer care. Eleven of the 12 items are used to create a summary score ranging from 0 to 44, with higher scores indicating better financial well-being. Validation studies have established clinically meaningful grades of financial toxicity: scores 26+ = grade 0; 14-25 = grade 1; &lt; 14 = grade 2; 0 = grade 3. Semi-structured interviews included questions on financial concerns, impacts on lifestyle, and other medical costs, including questions like "Has the financial cost of your cancer treatments up until this point affected your lifestyle?"
Quantitative analysis included COST-FACIT scores summarized as means, ranges, and standard deviations at each timepoint, including longitudinal change from baseline. Qualitative analysis included recording interviews, professional transcription, team-based codebook development, and systematic thematic analysis.
Results: We report on 28 patients enrolled from August 2020 to June 2021. For questionnaires, 26 completed baseline, 23 completed day 28 (1 patient died and 2 have not reached this timepoint), 12 completed day 90 (11 have not reached this timepoint), and 8 completed day 180 (16 have not reached this timepoint). For qualitative interviews, 16 completed baseline telephone interviews, 6 completed day 90 (10 have not reach this timepoint), and 4 completed day 180 (12 have not reached this timepoint). Median age was 57.7 years, 52% were male, 21% Hispanic/Latinx, 75% white, 8% Asian, and 4% Hawaiian/Pacific Islander. A majority of patients were (76%) married.
COST-FACIT scores were highest at baseline indicating higher financial well-being (mean 29), and also represented the largest range (range 8-44) suggesting patients come into CAR-T at different levels of financial toxicity, ranging from grade 0 to grade 2 (Figure 1). Average financial toxicity at Baseline and Day 28 corresponded to grade 0 toxicity. Financial well-being declined thereafter, elevating to grade 1 toxicity with the average score 25.2 at day 90 and 23.6 at day 180. At Baseline, Day 28, and Day 90 there are patients experience grades 0, 1, and 2 financial toxicity.
Qualitative themes include: Insurance, Lodging/Relocation, Work/Income, Nontraditional sources of funding, Discussion with Providers (Table 1). Preliminary assessment of thematic patterns over time supports the quantitative results, with patients expressing little to no financial concerns at baseline, often citing "great insurance", with changes at day 90 recognizing the additional costs not covered by insurance, and uncertainty of insurance coverage.
Conclusions: Our results using both quantitative and qualitative methods indicate the financial impact of CAR-T therapy extends beyond the cost of treatment. Patients undergoing CAR-T therapy experience financial toxicity, with its impact worsening with time as the stressors and payments cumulate. These data are important for understanding the full patient experience with CAR-T therapy and emphasize that durable support and resources are needed to help patients with financial toxicity. Concern for financial toxicity may limit access to this therapy and future research should focus on access to therapy based on personal financial concerns and referral patterns.
Figure 1 Figure 1.

Disclosures
Frank: Allogene Therapeutics: Research Funding; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Research Funding. Miklos: Pharmacyclics, Amgen, Kite, a Gilead Company, Novartis, Roche, Genentech, Becton Dickinson, Isoplexis, Miltenyi, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Biosciences, Adicet, Adaptive Biotechnologies: Research Funding; Adaptive Biotechnologies, Novartis, Juno/Celgene-BMS, Kite, a Gilead Company, Pharmacyclics-AbbVie, Janssen, Pharmacyclics, AlloGene, Precision Bioscience, Miltenyi Biotech, Adicet, Takeda: Membership on an entity's Board of Directors or advisory committees; Pharmacyclics: Patents & Royalties; Kite, a Gilead Company, Amgen, Atara, Wugen, Celgene, Novartis, Juno-Celgene-Bristol Myers Squibb, Allogene, Precision Bioscience, Adicet, Pharmacyclics, Janssen, Takeda, Adaptive Biotechnologies and Miltenyi Biotechnologies: Consultancy. Shah: Umoja: Consultancy; Miltenyi Biotec: Consultancy, Honoraria, Research Funding; Lily: Consultancy, Honoraria, Research Funding; Incyte: Consultancy; Kite: Consultancy; Legend: Consultancy; Epizyme: Consultancy. D'Souza: Imbrium, Pfizer, BMS: Membership on an entity's Board of Directors or advisory committees; Sanofi, Takeda, Teneobio, CAELUM, Prothena: Research Funding; Janssen, Prothena: Consultancy. Muffly: Pfizer, Amgen, Jazz, Medexus, Pfizer: Consultancy; Astellas, Jasper, Adaptive, Baxalta: Research Funding; Adaptive: Honoraria, Other: fees for non-CME/CE services: , Research Funding. Sidana: Allogene: Research Funding; Janssen: Consultancy, Research Funding; BMS: Consultancy; Magenta Therapeutics: Consultancy, Research Funding.