Geographical CAR-T Unmet Needs for Patients with Large B-Cell Lymphoma in the Province of Quebec

Introduction

Anti-CD19 CAR-T has revolutionized the outcome of patients with refractory and/or relapsing large B-cell lymphoma. Anti-CD19 CAR-T significantly improved their median overall survival (Neelapu et al. NEJM 2017, Schuster et al. NEJM 2019, Abramson et al. Lancet 2020) and has defined a standard-of-care in third line therapy. Results have been reproduced in real-world settings (Iacoboni et al. Cancer Med 2021, Jacobson et al. Transplant Cell Ther 2022) and the clinical implementation of this therapy is expanding worldwide. Commercially approved anti-CD19 CAR-T cell therapies require patients to be treated in specialized (FACT accredited) medical centres and to stay near these centres for the first 28 days once these are administered. As CAR-T cell therapies for lymphoma are only offered in three academic centres across the province of Quebec despite its population of 9 million people and its enormous geographic footprint, we hypothesized that these limitations would result in a geographic disparity in the delivery of care. Our aim was to evaluate the access to this innovative therapy in the province of Quebec.

Methods

We retrieved the postal codes of all patients living in the province of Quebec who received commercial CAR-T from its launch in August 14^th 2019 up until June 30^th 2022. We grouped these patients according to their respective administrative regions, taking into account their relative population densities. No difference in the incidence of lymphoma in Quebec is reported across administrative regions.

Results

Quebec covers a large territory of 1 667 441 km² divided in 17 administrative regions (figure 1). Maisonneuve-Rosemont Hospital was the first center to offer CAR-T cell therapy in Quebec and is located in the region of Montreal, followed by CHU de Québec - university Laval in the region of Capitale-Nationale and McGill University Health Centre also in Montreal. Between August 14^th 2019 and June 30^th 2022, 108 patients have been treated from 16 of the 17 administrative regions in Quebec. In 2019: 9 patients from 4 of the 17 administrative regions were treated, in 2020: 23 patients from 9 of the 17 regions were treated, in 2021: 47 patients from 12 of the 17 regions were treated and in the first semester of 2022: 29 patients from 13 of the 17 regions were treated. Table 1 depicts the administrative regions of the 108 patients of our cohort treated over our first 3 years of activity, the representation of each of these regions amongst our cohort and their share of the Quebec population. The administrative regions where the CAR-T centers are located (Montreal and Capitale-Nationale) contributed significantly to the number of patients infused, but the numbers are below expected based on the actual population. Following the opening of a second CAR-T cell unit in the Capitale-Nationale, patients from 3 new administrative regions were treated. Capitale-Nationale is located East of Montreal and the patients from these 3 new administrative regions (namely Bas-St-Laurent, Gaspésie-Îles-de-la-Madelaine and Nord-du-Québec) are further away from Montreal.

Discussion

Based on the incidence of large B-cell lymphoma in the province of Quebec and the outcomes following actual standard therapies, approximately 60 patients should be eligible for CAR-T in Quebec per year. Our results demonstrates that although CAR-T are available as standard-of-care in Quebec since August 2019, not all patients throughout the province have had access to this therapy probably because of many challenges patients face to obtain this potential beneficial therapy. Although the COVID-19 pandemic has been a significant impediment, we believe that competitive trials, reduced referrals due to strict eligibility criteria and patients' reluctance to travel away from their home represent significant limitations. In order to facilitate the implementation of an expected increasing number of indications for CAR-T, our data provide basis to survey patients and healthcare workers in Quebec to better understand the limitations to the implementation of this therapy in a geographically large region such as the province of Quebec.

Fromentin:Kite-Gilead: Speakers Bureau. Sebag:BMS: Consultancy; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding. Couture:Novartis: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Larouche:Abbvie: Research Funding; German: Research Funding; Incyte: Research Funding; Kite-Gilead: Research Funding; Astrazeneca: Research Funding. Lemieux:AbbVie: Consultancy, Speakers Bureau. Cohen:ExCellThera: Consultancy, Patents & Royalties, Research Funding. Veilleux:Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Honoraria, Membership on an entity's Board of Directors or advisory committees. Fleury:Seagen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees, Research Funding; Roche: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kite-Gilead: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; AbbVie: Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Incyte: Membership on an entity's Board of Directors or advisory committees, Other: Grant during the conduct of the study , Research Funding, Speakers Bureau; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; AstraZeneca: Membership on an entity's Board of Directors or advisory committees, Research Funding; Beigene: Membership on an entity's Board of Directors or advisory committees, Research Funding.