Estimation of eligibility for and response to CAR-T therapy in the United States

Abstract

Chimeric antigen receptor (CAR) T-cell (CAR-T) therapies genetically modify a person's own T cells to bind to antigens expressed on cancer cells. 1,2CAR-T has generated sizable enthusiasm because of early reports of dramatic and sustained response. 3Since 2017, 6 CAR-T products have been approved by the Food and Drug Administration (FDA), and other indications for a wide variety of tumors, including solid cancers, are actively being tested. [4][5][6][7] CD19 CARs have been associated with high response rates and a fraction of patients experiencing durable complete remissions. 8,9B-cell maturation antigen CARs have hitherto been associated with high response rates but concerningly high rates of eventual relapse.For these reasons, and consistent with prior works, which have examined genome driven therapies, checkpoint inhibitors, and cytotoxic drugs, [10][11][12][13] we sought to estimate the percentage of patients in the United States with advanced or metastatic cancer who may be eligible for and respond to CAR-T therapies.We considered a person as being eligible for CAR-T therapy if they had the tumor type and notable inclusion criteria for the drug approval.In accordance with 45 Code of Federal Regulations section 46.102(f), this study was not submitted for institutional review board approval because it involved publicly available data.In order to estimate the number of persons in the United States with advanced or metastatic cancer who were eligible, according to the approval indications, we used death data for the respective tumor type from the American Cancer Society's Cancer Facts and Figures. 14These data were used as a stand-in for eligibility because these therapies are often administered in later lines when other frontline drugs and therapies have been unsuccessfully used.We abstracted data corresponding to the years the individual malignancy types had a CAR-T therapy approval, through 31 March 2023.Because several indications were approved for a more specific tumor type than that used for death data, we searched the peer-reviewed literature for specific prevalence estimates for those tumor types.For eligibility, we assumed that 20% of patients with multiple myeloma progressed to fourth line or later. 15We assumed that 22% of non-Hodgkin lymphoma (NHL) was follicular lymphoma; 16 3% of NHL was mantle cell lymphoma; 16 and 75% of patients with NHL had large B-cell lymphoma (after subtracting follicular and mantle cell lymphomas).For B-cell precursor acute lymphoblastic leukemia, we assumed that 75% of acute lymphoblastic leukemia cases were of the B-cell lineage. 17,18r all CAR-T therapies approved by the FDA, we used package inserts to identify trial data, indication, and the reported overall response rate.Response rates were based on complete and partial responses, including complete remission with or without complete hematologic recovery.We divided the number of cancer-specific deaths for which there was an FDA-approved CAR-T therapy by the total number of all cancer deaths to estimate the percentage of people who were eligible for CAR-T therapy.

Topics & Concepts