Impact of Patient Distance from Center on Outcomes and Cost of Therapy for Patients Undergoing Chimeric Antigen Receptor T-Cell Therapy for B-Cell Lymphoma
Authors: Hoeynck Brian , Bhaskar Shakthi , Jallouk Andrew P , Dholaria Bhagirathbhai , Savani Bipin N. , Oluwole Olalekan O. , Morgan David , Sengsayadeth Salyka M. , Kassim Adetola A. , Patel Vivek 
Published: December 2024

BACKGROUND:
Chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape for B-cell non-Hodgkin lymphoma (B-NHL). Results from recent studies have expanded patient access to CAR-T; however, treatment is only given at specialized centers. Little data is available evaluating the impact of distance from the CAR-T center on outcomes or cost for patients receiving CAR-T.
METHODS:
Patients (pts) aged ≥18 years with B-NHL who were referred either internally or externally between November 2017 and March 2023 for commercial CAR-T at Vanderbilt Medical Center were included. Pts who died prior to leukapheresis or infusion were not excluded. Date of referral was defined by presentation at an internal consensus meeting shortly after the initial provider visit. Other key time points were date of leukapheresis and date of CAR-T infusion. Brain to vein (B2V) time was defined by time from referral to CAR-T infusion.
Kaplan Meier method was used for survival outcomes. Results were stratified by home distance from the medical center (within 90 miles or greater). Infection data including need for hospitalization was collected for 12 months after CAR-T infusion. Descriptive statistics are reported.
Post referral therapy included treatment given between referral and leukapheresis, and bridging therapy included treatment given after leukapheresis. A crude cost estimate of therapies prior to CAR-T infusion was performed. Dollar amounts were obtained by review of CMS and previously published studies.
RESULTS:
A total of 61 pts intended to receive axicabtagene ciloleucel (79%), tisagenlecleucel (7%), or brexucabtagene autoleucel (15%) with a median follow up of 17 months. There were 14 pts (23%) who died while awaiting leukapheresis. The median age at referral was 60 (range 22-84). More pts had relapsed disease (43%) than relapsed/refractory (22%) or primary refractory disease (35%). Most patients had stage 3 or 4 disease (72%) and elevated LDH (75%). Private insurance (63%) was more common than Medicare (37%). The median distance from the CAR-T center was 139 miles (range 3-618). There were 40 pts (66%) who lived greater than 90 miles from the center (long distance) and 21 pts (34%) who lived closer (close distance).
The median time from referral to leukapheresis and B2V time were similar between distance groups (65 days and 96 days in the close distance vs. 72 days and 100 days in the long distance). There was no significant difference with respect to death prior to leukapheresis between close distance and long distance groups (19% vs. 25%)
Most pts (85%) required post-referral therapy and many pts (21%) required two or more lines. Post referral therapy regimens were platinum-based (39%), polatuzumab-based (29%), other systemic chemotherapy (16%), oral targeted agents (16%), and radiation (1%). Few pts (35%) required bridging therapy after leukapheresis. There were no differences in post referral treatment by distance. Excluding costs for leukapheresis and CAR-T infusion, the median cost of post-referral and bridging therapies was $23,900 USD and there were no differences by distance from the center.
The 12 month progression free survival (PFS) was 75% (CI: 56% - 87%) for the long distance group compared to 82% (CI: 55% - 94%) in the short distance group. There was a trend towards inferior 12-month overall survival (OS) for the long distance group (55%, CI: 39% - 69%) compared to the short distance group (71%, CI: 47% - 86%). Non relapsed mortality (NRM) was numerically higher in the long distance group (n=6, 20%) compared to the short distance group (n=1, 5%). There were 6 deaths related to infection in the long distance group and no deaths from infection in the short distance group. At 1 year after CAR-T infusion, there were 11 pts (39%) with infections requiring hospitalization in the long distance group compared to 3 pts (20%) in the short distance group.
CONCLUSION:
In this intention to treat analysis, we showed that longer distances from CAR-T centers may be associated with inferior infection and survival outcomes. Time from referral to CAR-T infusion is longer than expected; however, is not affected by patient distance from the center. NRM was high in this cohort and infection related deaths were more common for patients who lived more than 90 miles from the CAR-T center. Future multicenter studies should be conducted to better understand barriers to access and supportive care for patients undergoing CAR-T therapy.