Identification of Barriers of CAR-T Utilization in Patients with Diffuse Large B-Cell Lymphoma
Authors: Awan Farrukh T. , Belli Andrew J. , Hansen Eric , Chung Mimi , Wang Ching-Kun 
Published: November 2021

Abstract
Introduction:
The advent of CAR-T cell therapies have significantly improved outcomes of patients with relapsed/refractory B-cell malignancies - particularly those with diffuse large B-cell lymphoma (R/R DLBCL) with chemorefractory disease. However, despite the early promise and improved access, utilization of commercially approved CAR-T treatments has lagged behind early estimates generated by historical outcomes of patients with R/R DLBCL. The influences and challenges that limit utilization of CAR-T treatments and practice-specific treatment patterns in CAR-T-eligible patients have also not been studied systematically. Herein we provide comprehensive comparative characteristics, treatment patterns, and outcomes of patients with R/R DLBCL who would be deemed eligible for CAR-T therapy, per the criteria utilized in pivotal clinical trials performed for commercial approval of these agents.
Methods:
This retrospective study utilized the COTA real-world database, a de-identified database of RWD derived from the electronic health records of partnered healthcare providers in the United States. A total of 1663 patients treated for DLBCL after 2016 were included in the analysis. Patient and disease outcomes, therapy utilizations and comparative outcomes with respect to clinical trial criteria were extracted and analyzed descriptively. Line of therapy was assigned programmatically utilizing standard definitions and guidelines. Survival and mortality outcomes were assessed by KM method across various subgroups.
Results:
In the 1663 patients with DLBCL included in this study, the median age was 66 years (IQR: 56-75). 58.9% were males and 73.6% were Caucasians. Practice setting distribution of this cohort was 50.6% academic and 49.4% community. 7.9% of the population (N=131) had primary refractory disease and 45.1% had relapsed disease, including 4.5% (N=75) who relapsed following autologous stem cell transplantation (ASCT). Most common histology was DLBCL not otherwise specified, 31.1% had bulky disease and 69.3% had extranodal disease at initial presentation. Double- or triple-hit status was not assessed in 52.0% of patients. With a median follow up of 1.8 years, the 12-month overall survival (OS) from time of starting first line treatment of the entire cohort was 84%. Patients with primary refractory disease had a median OS of 21.2 months and patients with relapsed disease post ASCT had a median OS of 33 months. We further evaluated the outcomes of 145 patients who underwent CAR-T therapy (8.7% of the entire cohort) and compared outcomes to 169 patients who did not undergo CAR-T therapy despite meeting the eligibility criteria utilized in the pivotal ZUMA-1 or JULIET trial for axicabtagene cilolecleucel and tisagenlecleucel respectively (10.1% of the entire cohort). Patients who did not undergo CAR-T therapy were older (median age 63 vs. 59 years respectively, p=0.031) and almost all in the academic setting (96.4% vs 56.6% respectively, p&lt;0.001). The rest of the demographics and comorbid conditions were similar between the 2 groups. A higher proportion of patients in the group that did not proceed to CAR-T had stage 1-2 disease at diagnosis (27.2% vs 14.5% respectively, p&lt;0.001), ECOG performance status of 0-1 (100% vs 51.0%, p&lt;0.001), normal LDH (52.1% vs. 19.3%, p&lt;0.001). With a median follow up of 3 years, the 12-month OS was 91% in this cohort, and compared favorably for patients undergoing CAR-T for whom the median PFS, 12-month OS, and 12-month NRM was 9.3 months, 94%, and 6.8% respectively at a median follow up of 2.0 years. These patients were treated with various additional therapies the details of which will be presented at the meeting.
Conclusions:
Our study details the characteristics of a real-world population of patients with DLBCL and evaluates outcomes specifically with respect to CAR-T therapy utilization. Outcomes of patients undergoing CAR-T therapies are similar to previously reported data. While retrospective reviews are limited in their ability to truly assess all patient and physician factors that influence therapeutic selection, our study highlights clinical characteristics of potentially eligible patients who do not undergo CAR-T treatment. Furthermore, it provides an avenue to compare outcomes of novel therapies in the relapsed setting especially when compared to CAR-T treatment and the promising survival outcomes observed presumably due to their use.

Disclosures
Awan: Verastem: Consultancy; ADCT therapeutics: Consultancy; Incyte: Consultancy; MEI Pharma: Consultancy; Abbvie: Consultancy; Cardinal Health: Consultancy; Merck: Consultancy; BMS: Consultancy; Beigene: Consultancy; Kite pharma: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Pharmacyclics: Consultancy; Gilead sciences: Consultancy; Janssen: Consultancy; Johnson and Johnson: Consultancy; Astrazeneca: Consultancy; Dava Oncology: Consultancy; Genentech: Consultancy. Belli: COTA, Inc.: Current Employment, Other: Equity ownership. Hansen: COTA, Inc.: Current Employment. Chung: COTA, Inc.: Current Employment. Wang: COTA, Inc.: Current Employment, Other: Equity ownership.