Increased CAR-T Infusions Occur in Conjunction with Decreased Hematopoietic Stem Cell Transplantation

Abstract

Background: Chimeric Antigen Receptor T-cell (CAR-T) therapies were first approved by the FDA in 2017, and multiple commercial products are currently available. Hematopoietic stem cell transplantation (HSCT) is another treatment strategy often utilized for patients with advanced and/or relapsed hematologic malignancies. Both CAR-T and HSCT require significant, overlapping resources for their collection, storage, and processing. Understanding the impact of evolving standards of care in clinical practice is necessary in the planning of resource allocation and laboratory expansion. We aimed to characterize the trends of CAR-T and HSCT infusions over a five-year period. Methods: The processing lab database was reviewed to compile a list of patients that received either CAR-T or HSCT (autologous or allogeneic) infusions, between 01/01/2018 and 12/12/2022. The number of individual HSCTs and CAR-T infusions were plotted over time. We also calculated the percent contribution of both HSCT and CAR-T to the total number of products infused per year. We subsequently examined these parameters, within the specific diagnoses of diffuse large B-Cell lymphoma/large cell lymphoma (DLBCL/LCL, including double and triple hit DLBCL and High-Grade lymphoma) and multiple myeloma (MM), including MM with amyloid and MM with plasma cell leukemia/plasmacytoma. Simple linear regression was used to calculate statistical significance to determine if the slopes were non-zero, and the direction of change over time. Results: Overall, our study included 210 CAR-T infusions and 2366 HSCTs. 89/210 (42%) patients who received a CAR-T product also received HSCT between 2018 and 2022, with 85/89 receiving HSCT prior to CAR-T infusion and 4/89 receiving CAR-T prior to HSCT, including two patients who received HSCT before and after CAR-T. The median interval between the most recent HSCT and subsequent CAR-T was 37 months. DLBCL/LCL and MM were the disease indications for which CAR-T was most utilized, accounting for 87.6% of the 210 procedures. The total number of CAR-T procedures increased significantly over the five-year period, from 24 in 2018 to 74 in 2022 (Slope=13.8; p=0.02), accompanied by a marked decrease in the number of HSCT from 502 in 2018 to 393 in 2022 (Slope=-26.6; p=0.06). The overall number of infusions (calculated as number of HSCT + number of CAR-T) declined slightly, though this was not statistically significant (mean 511 + 30.6 per year; Slope=-12.8; p=0.22). When expressed as a percentage of the total number of infusions, we observed a significant increase in the proportion of CAR-T, from 4.6% in 2018 to 15.8 % in 2022, (Slope=2.98; p=0.02), and a significant decrease in the proportion of infusions that were HSCT, from 95.4% in 2018 to 84.2% in 2022 (Slope=-2.98; p=0.02). In DLBCL, we observed a slight decrease in the number of overall infusions, from 71 in 2018 to 58 in 2022 (Slope=-3.5; p=0.18) and a significant decrease in HSCT from 47 in 2018 to 26 in 2022 (Slope=-6.0; p=0.0172), while the number of CAR-T infusions remained stable (mean=27.4 + 5.3 per year; Slope=2.5; p=0.14). In MM, we observed a marked increase in CAR-T infusions, from none in 2018 to 33 in 2022 (p=0.0544), while the total number of infusions remained stable (Mean 231.8 + 16.54; slope=-3.5; p=0.58) and HSCT slightly decreased, from 228 in 2018 to 184 in 2022, though this was not statistically significant (Slope=-11.5; p=0.18). We observed a non-significant increase in the percent contribution of CAR-T to the total number of infusions performed for MM, from 0% in 2018 to 15.3% in 2022 (Slope=3.62; p=0.06) while in DLBCL we observed a significant increase, from 33.8% in 2018 to 55.2% in 2022 (slope=6.42; p=0.017). Conclusion: The findings from this study suggest a gradual trend in the clinical utilization of human cellular therapy products over time. Since many of the resources and personnel involved in the collection, storage, and processing of these products are shared, an increase in CAR-T is an important observation. These findings underscore key issues in lab management for cell manufacturing facilities when considering resource allocation and infrastructure development. More analysis is needed to determine if the decrease in HSCT and the increase in CART are related.