Patient Characteristics and Treatment Patterns for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) By CAR T Eligibility and Treatment Status in France, Germany, Italy, Spain, the UK, and Japan
Authors: Park Andrew , Cooper Selin , Mpima Sheila , Casey Vicky , Chatu Moulika , Nunes Ângela , Manuguid Fil , Liede Alexander 
Published: December 2024

Introduction: Although most patients (pts) with DLBCL will be cured with first-line chemoimmunotherapy, those with relapsed/refractory (R/R) disease have poor prognoses. The emergence of chimeric antigen receptor T-cell therapy (CAR T) has changed the treatment landscape for pts with R/R DLBCL, offering improved response and survival outcomes vs historical standard of care. However, there are limitations to CAR Ts that may impede their widespread utilization, including a serious side-effect profile, high treatment costs, required travel to a certified treatment center, and substantial logistical burdens and challenges. Determining pt eligibility also requires careful consideration of overall fitness, comorbidities, and organ function. Herein, we report clinical characteristics and previous treatment patterns of pts with R/R DLBCL deemed eligible for CAR T and their treatment status (ie, CAR T not planned, planned, or ongoing) in France, Germany, Italy, and Spain (EU4), the United Kingdom (UK), and Japan.
Methods: Hematology/oncology specialists treating R/R DLBCL in EU4, the UK, and Japan participated in a retrospective cross-sectional study from April to June and October to December of 2022 and 2023 as part of IQVIA CAR T-Cell Monitor. Pts with CAR T ongoing were reported by a panel of physicians from CAR T-accredited sites, while pts receiving non-CAR T treatments were reported by physicians from both accredited and non-accredited sites. Physicians reported on pt diagnoses, clinical characteristics, and ongoing and prior treatment regimens for pts treated in the previous 6 months. Findings were stratified by region (EU4/UK or Japan) and by reported CAR T treatment status (eligible but not planned, planned, or ongoing).
Results: 377 hematology/oncology specialists provided data on 986 pts with R/R DLBCL who were eligible for or currently receiving CAR T. Of these pts, 169 total (147 EU4/UK, 22 Japan) were eligible but not planned for CAR T; 156 total (120 EU4/UK, 36 Japan) were planned for CAR T, and 661 total had CAR T ongoing (587 EU4/UK, 74 Japan). More pts were eligible but not planned for CAR T vs planned or ongoing, respectively, who were &gt;65 years old (EU4/UK: 50% vs 42% and 28%; Japan: 73% vs 28% and 16%) and considered frail (EU4/UK: 26% vs 14% and 11%; Japan: 50% vs 8% and 16%). The proportion of pts with Eastern Cooperative Oncology Group (ECOG) performance status 0-1 was similar across the eligible but not planned, planned, and ongoing CAR T groups in EU4/UK (83%, 86%, and 83%, respectively); however, in Japan, a lower percentage of pts eligible but not planned for CAR T had ECOG status 0-1 (64%) vs those with CAR T planned (86%) or ongoing (92%). In the EU4/UK, 42% of CAR T eligible but not planned, 50% of CAR T planned, and 41% of CAR T ongoing pts had no preexisting comorbidities. In Japan, a slightly smaller proportion (45%) of CAR T eligible but not planned pts had no preexisting comorbidities vs 56% of CAR T planned and 58% of CAR T ongoing pts. Stem cell therapy (SCT) eligibility status varied by CAR T status and region: in EU4/UK, 24% of CAR T eligible but not planned, 21% of CAR T planned, and 22% of CAR T ongoing pts were ineligible for SCT; in Japan, these values were 50%, 25%, and 58%, respectively. Previous treatments received also varied by CAR T status and region. In EU4/UK, the proportion of pts who had received second-line (2L) immunotherapy was similar among those who were CAR T eligible but not planned (7%), planned (6%), and ongoing (9%). In Japan, a larger proportion of CAR T eligible but not planned pts were treated with 2L immunotherapy (20%) vs CAR T planned (3%) and ongoing (10%) pts. In the EU4/UK, 55%, 70%, and 54% of pts in the CAR T eligible but not planned, planned, and ongoing groups, respectively, were treated with chemotherapy and rituximab-based regimens in 2L; in Japan, these proportions were 55%, 53%, and 51%.
Conclusion: CAR T utilization remains hampered by limitations in access for pts. Results of this study suggest physicians select pts for CAR T with better fitness, lower ECOG performance status, younger age, and fewer comorbidities. These findings highlight a persistent unmet need in the European Union, the UK, and Japan for novel treatment options, particularly for pts who may be eligible for CAR T but are not selected to receive treatment.