Real world data to identify target population for new CAR‐T therapies

Abstract

Purpose Diffuse large B‐cell lymphoma (DLBCL) is an aggressive lymphoma often refractory to currently available treatments (immuno‐chemotherapy/autologous‐stem‐cell‐transplantation‐ASCT). Recently, new cell therapies have been approved for patients failing two conventional treatments, CAR‐T (Chimeric‐Antigen‐Receptor‐T‐cell), committing payers in planning and implementing their use. We aim to define, using Real World Data (RWD), a reproducible procedure that allows identification of CAR‐T target population for DLBCL. Methods Through the linking of electronic healthcare datasets (EHD), we identified patients with non‐Hodgkin's Lymphoma (NHL), resident in Lazio region (2010–2015), aged ≥20 years. DLBCL patients were followed using pathological anatomy (PA) reports, up to 3 years. To be defined as relapsed after two treatment lines, patients must have had new chemotherapy and/or NHL hospitalization after ASCT or at the end of the second chemotherapy. The incident rate of second relapse (R2‐rate) was extended to the population without PA reports. Result NHL incident patients were 7384, 68% presented a PA report and, 29% of these had DLBCL codes. Patients who relapsed after two treatment lines were 47 (39%) in the subgroup of patients who received ASCT and 138 (41%) in that with second chemotherapy treatment. Patients in the two subgroups were very different in terms of age and comorbidity. The annual incident number of DLBCL was estimated to be 329 which multiplied by R2‐rate (13.7%) gives 45 patients per year eligible for CAR‐T. Discussion This study shows how RWD allows the identification of a target population with new advanced therapies. This approach is rigorous, transparent and verifiable over time.

CAR T-Cell Therapies in Italy: Patient Access Barriers and Recommendations for Health System Solutions

“…This corresponds to an incidence rate of 7.6 per 100,000 inhabitants, which is comparable to other estimations for Italy ( Heine et al, 2021 ). Of these DLBCL patients, 4,058 (89%) are estimated to have received first-line therapy ( Belleudi et al, 2021 ), and 1,542 (34%) to have been treated in second-line after relapse or being refractory to first-line therapy. 638 DLBCL patients (14%) are estimated to have relapsed or have been refractory after two lines of systemic therapy, which corresponds to the EMA-approved indication for CAR T-cell therapies ( Belleudi et al, 2021 ; Di Rocco et al, 2021 ).…”

“…Of these DLBCL patients, 4,058 (89%) are estimated to have received first-line therapy ( Belleudi et al, 2021 ), and 1,542 (34%) to have been treated in second-line after relapse or being refractory to first-line therapy. 638 DLBCL patients (14%) are estimated to have relapsed or have been refractory after two lines of systemic therapy, which corresponds to the EMA-approved indication for CAR T-cell therapies ( Belleudi et al, 2021 ; Di Rocco et al, 2021 ). Of note, other estimations for Italy ( Heine et al, 2021 ) as well as from the French Haute Autorité de Santé ( HAS, 2021b ; 2021a ) report a higher percentage (17%) of DLBCL patients relapsed or refractory after two lines of systemic therapy, which would correspond to 775 Italian patients in 2020.…”

Barriers to patient access of CAR T cell therapies in Austria

“…Since at the time of writing both recent and specific public data on DLBCL incidence and treatment patterns were not available in Austria, published estimations from France [35] and Germany [34] were used to approximate the DLBCL incidence in Austria, as well as patient flow in first, second and third line. The proportion of CAR T eligible patients in Austria was estimated based on estimations for France [35], the Netherlands, Austria, Spain, and Italy [36,37] as well as recent real-world analyses [48][49][50][51]. Data on the use of CAR T cell therapies in Austria have been retrieved from recently published reports.…”

“…Around 16% (89 of 556) of DLBCL patients are estimated to be refractory or in relapse after 2 previous lines of therapy based on the estimations for Germany [34], France [35], and the USA [54], which would represent the EMA-approved DLBCL CAR T population of 89 patients per year in Austria [4,5]. When also applying eligibility criteria as used in the registrational trials and specified by the Austrian CAR T algorithm, approximately 10% (56 of 556) of all incident DLBCL patients are estimated to qualify for CAR T cell therapy per year based on the estimation for France [35], the Netherlands, Austria, Spain, Italy, and recent realworld data [36,37,48,50,51,57].…”

“…This corresponds to the EMA DLBCL label indication for licensed CAR T products [4,5] 10% of DLBCL patients estimated to be eligible for CAR T cell therapy base on the registrational trial criteria, based on estimation for France (Haute Autorité de Santé, [35]) and the Netherlands, Austria, Spain [36] and Italy [37] DLBCL patients eligible for licensed CAR T products under clinical trial criteria (Austrian CAR T algorithm)…”