CAR-T-cell-therapies (CARTs) have transformed the therapeutic landscape of B- and plasma cell malignancies. However, misconceptions of “CART-eligibility”, the logistical burden and significant costs associated with CARTs complicate access. There is a scarcity of data on how readily eligible patients gain access to CARTs outside of clinical trials. We analyzed real-world CART data from our center to understand patterns of patient referral and thereby try to delineate potential obstacles keeping eligible patients from receiving CARTs.

We identified patients treated at LMU University Hospital by searching the electronic records for relevant procedural codes. Patients who received CARTs in clinical trials were excluded. German cancer registry data (GCRD) were exported from the Center for Cancer Registry Data at the Robert Koch Institute, which pools data from all German state-level cancer registries. Statistical analyses were performed using R version 4.4.1. This retrospective analysis was approved by the relevant ethics committee and was conducted in accordance with the declaration of Helsinki.

Between 2018 (year of first CART approval in the European Union) and 2024, a total of 218 patients were evaluated for CARTs outside of clinical trials at our center. Of those, 44 were not treated with CARTs (33/44 due to early progression/death ). Of those, 19 had already undergone apheresis. The percentage of those evaluated but not treated decreased over the years (14/38 [37%] in 2019 versus 9/64 [14%] in 2024).

The number of patients treated per year increased over time (24 in 2019 vs. 55 in 2024). Median age of patients who received CARTs was 63 years (range 20 - 86). 69 patients (40%) were female. Within entities, the sex distribution of treated patients was close to the incidence reported by German cancer registries (e.g. 46% (our data) vs. 44% (registry) female in diffuse large B-cell lymphoma (DLBCL)). Overall, DLBCL was the most common indication (64%), followed by multiple myeloma (MM, 14%). As CARTs were approved for more entities, the landscape shifted. In 2019, 19/24 (79%) patients were treated for DLBCL, whereas this entity only made up 58% (32/55) of patients treated in 2024, with follicular lymphoma (FL), mantle cell lymphoma (MCL) and especially MM becoming more common.

Median vein-to-vein time (v2v) decreased over the years, but product-specific differences were maintained (axicabtagen-ciloleucel v2v 2019 vs. 2024 33 vs. 31 days, lisocabtagen-maraleucel v2v 2023 vs. 2024 47 vs. 41 days). Over the years, the median duration of hospitalization shortened significantly (2019 vs. 2024: 31 vs. 21 days, p=0.003). ICU admissions decreased considerably (21% vs. 11%), but the median length of ICU stay did not change (9 vs. 12 days, p = 0.8).

We categorized patients by referrer: internal referral from our center vs. external referral from other hospitals or private practices. The percentage of external referrals for CART-evaluation increased from 2019 to 2024 (32% vs. 48%), which was even more pronounced for those who received CARTs (12% vs. 55% of externally referred patients). Internally referred patients were more likely to receive CARTs after being evaluated (85% vs. 70%, p = 0.008). However, this association was only present for patients treated between 2018 and 2021 (88% vs. 44%, p = 0.001) and disappeared for those evaluated in 2022-2024 (p = 0.5). The age distribution of internally vs. externally referred patients was not significantly different, neither for evaluated nor treated (n = 174) patients. Median ECOG was not significantly different for internal and external patients (median ECOG 1 for both, p= 0.9). The percentage of externally referred patients with DLBCL increased over time (2019 vs. 2024: 33% vs. 56%, p = 0.009), while this percentage is lower for FL and MCL (for 2024: 33% and 29% respectively).

Taken together, the rate of external referral for CARTs to LMU university hospital increased from 2019 to 2024, potentially due to a broader acceptance of CARTs as a valid therapy option. Characteristics of externally referred patients were not significantly different from those internally referred. From our data, we therefore cannot derive specific referral obstacles for CART candidate patients treated outside CART-performing centers. In conclusion, shorter v2v intervals, shorter hospitalizations and fewer ICU-admissions make CARTs a viable option for an increasing number of patients.

This content is only available as a PDF.
2025
Sign in via your Institution