French Regional Experience of Pre-CAR-T Cells Lymphodepleting Chemotherapy Outcourced in the Patient's Referring Center
Authors: Dumont Anne , Beziat Guillaume , Gadaud Noemie , Ghenim Leila , Gauthier Martin , Thomazeau Joséphine , Vergez Francois , Spinau Coline , Vicente Céline , De Barros Sandra , Despas Fabien , Rey Solène , Pajiep-Chapda Marie Christelle , Guenounou Sarah , Cazaux Marine , Borel Cecile , Perrot Aurore , Ysebaert Loic , Recher Christian , Huynh Anne , Bories Pierre 
Published: December 2024

Background
CD19 and BCMA CAR-T cells have not only transformed the therapeutic landscape of relapse or refractory (R/R) lymphoid malignancies but also generated major transformation in patient (pt) journey and healthcare center-to-center coordination. French health authorities have restricted their use to inpatient administration in a limited number of around 40 qualified centers. The hospitalization capacity of these centers has not increased as fast as the number of CAR-T cells indications, which may generate barriers to timely management of R/R pts. Pre-CAR-T lymphodepletion (LD) is an essential step as it maximizes engraftment, efficacy and long-term survival of CAR-T. LD mainly relies on drugs well known by hematologists: Fludarabine (Flu) and cyclophosphamide (Cy). In order to reduce hospitalization times in the qualified center and increase its capacity, the Toulouse University Hospital and the West Onco-Occitanie cancer network have set-up a pt pathway in 2022 for B-cell lymphoma and myeloma pts, with outsourced LD in the referring center (ref-LD). Decision to outsource the LD was based on physicians' judgment for each individual pt.
Aims
To explore the outcome of R/R pts with B-cell malignancies infused with CD19 or BCMA CAR-T after the administration of ref-LD in their center of origin and to compare with those of pts infused after receiving the LD in the qualified center (qual-LD).
Methods
We retrospectively analyzed adults pts from the regional CARAVAGE registry (NCT06369389) infused with commercial CAR-T products, and focused on pts with outsourced LD in their referring center. The primary endpoint was hospital length stay in the CAR-T qualified center. The secondary endpoints were best ORR and CRR, grade≥3 CRS and ICANS rates, PFS, OS and CAR-T expansion (Cmax) and persistence (AUC-28d). All time-to-event analyses were carried out on the period 2022-2024 using time of CAR T-cell infusion as the origin.
Results
Between July 2019 and April 2024, 163 consecutive adults pts with R/R B-cell malignancies were infused with a CD19 or BCMA CAR-T cells and registered in the CARAVAGE registry, including 100 large B cell lymphoma (LBCL; 61.3%), 9 follicular lymphoma (FL; 5.6%) , 18 mantle cell lymphoma (MCL; 11.1) and 36 multiple myeloma (MM; 22.1%). Of those, we identified 34 pts (20.8%) receiving ref-LD in 9 different secondary healthcare centers and 129 pts receiving qual-LD (79.2%). As a reflection of pt selection, the ref-LD group included pts with more mature lymphoïd malignancies: 13 MM (38.2%) and 4 FL (19%) compared to 23 MM (17.8%) and 5 FL (4.7%) in the qual-LD group (p=0.01) and were more often responders to the bridging therapy: 38.2% versus 15.5% (p=0.003), respectively. The 2 groups were well balanced in terms of age, gender, number of prior lines, prior autologous transplant, performance status, HCT-CI score, CAR-HEMATOTOX score and bulky disease. All pts received Flu/Cy LD in accordance with manufacturer specifications. Among the 34 pts of the ref-LD group, 2 pts received 2 procedures of LD as they experienced infectious event after the first procedure (1 covid and 1 bacteriemia).
Hospital length stay was significantly reduced in the ref-LD group with a median of 14 days (range 10-23) compared to 20 days (range 14-69) in the qual-LD group, p&lt;0.001.
Among 163 pts evaluable for response, best OR/CR rates were similar between the 2 groups, at 77.2% and 51.9% in the ref-LD group versus 80.4% and 62.3% in the qual-LD group, with p-values at 0.93 and 0.27, respectively. We did not observe any difference in terms of G≥3 CRS and ICANS, which occurred in 2.9% and 8.8% of the ref-LD group versus 13,7% and 5,5% in the qual-LD group, p=0.56 and 0.06 , respectively. With a median follow-up of 6 months, among 122 pts evaluable for survival, on the time period 2022-2024, the estimated median PFS was 13 months (95% CI; 5 - NR) with ref-LD and 11 months (95% CI; 7-NR) with qual-LD (p=0.48) and the estimated median OS was 16 months (95% CI; 12 - NR) with ref-LD and 18 months (95% CI; 13 -NR) with qual-LD. Monitoring of circulating CAR-T cell is pending and will be presented during the meeting.
Conclusion
Outsourcing of pre-CAR-T LD in the referring center is a feasible strategy for selected patients to significantly reduce hospital times in the qualified center without compromising treatment safety and efficacy. Prospective cost efficiency analysis of this 2 pt pathways is planned including quality of life comparison.