Chimeric Antigen Receptor T-Cell Therapies: Barriers and Solutions to Access

Abstract

Chimeric antigen receptor T-cell (CAR-T) therapies are relatively new treatments for patients with heavily pretreated hematologic malignancies. Although these innovative therapies can offer substantial benefit to patients with limited alternative treatment options, patient-access barriers exist. Conventional clinical trials are time-consuming and may be limited by strict patient eligibility criteria, resources, and availability of enrollment slots. Because of the complexity of the CAR-T administration process, treatment delivery can be associated with additional burden for the patient, including requiring patients to reside close to treatment centers and remain with a caregiver after infusion. Manufacturing of CAR-T cells is completed in specialized facilities and depends on the availability of reagents, manufacturing workforce, and timely transportation. CAR-T therapy is costly, and many US health plans restrict coverage of cell and gene therapies. Several of the existing challenges because of these barriers have been exacerbated during the COVID-19 pandemic. This review discusses these barriers and proposes some potential solutions to improving patient access, including innovation in clinical trial design and manufacturing, location of treatment delivery, and key stakeholder opinions regarding treatment and reimbursement. We propose a call to action for key stakeholder groups to address these barriers to CAR-T therapy to expand treatment access for patients. Future collaboration between key stakeholders, including payers, regulatory agencies, and industry/academia, will be critical to continue to address these barriers and enhance patient access to these therapies.

Innovation in BCMA CAR-T therapy: Building beyond the Model T

“…In contrast, prolonged “brain-to-vein” times between CAR-T consultation and cell infusion remain a stubbornly persistent barrier to the success of BCMA CAR-T therapy. Some of the difficulties early in brain-to-vein intervals include high patient demand, limited slot availability for apheresis, and scarce inpatient beds for post-infusion toxicity monitoring ( 98 , 99 ). However, the bulk of brain-to-vein intervals is comprised by “vein-to-vein” times between T-cell apheresis and CAR-T infusion, which often span 2-3 months for patients currently receiving commercial BCMA CAR-T therapies.…”

Development of Ingenui-T, a Novel Vein-to-Vein Solution for Rapid Autologous CAR T-Cell Manufacturing Starting From Whole Blood, for the Treatment of Autoimmune Diseases

“…The challenges encountered in obtaining an optimal leukapheresis starting material for CAR T-cell manufacturing encompass operational hurdles like access to specialized apheresis centers that meet guidelines along with resourced and trained staff, 2 and technical issues such as vascular access, contamination from other cell types, and effectively managing adverse events during the collection process. 3 Furthermore, conventional CAR T-cell manufacturing involves a protracted culture of patient apheresis material over 7-10 days designed to maximize expansion, resulting in a final product with a highly differentiated T-cell phenotype.…”

“…The challenges encountered in obtaining an optimal leukapheresis starting material for CAR T-cell manufacturing encompass operational hurdles like access to specialized apheresis centers that meet guidelines along with resourced and trained staff, 2 and technical issues such as vascular access, contamination from other cell types, and effectively managing adverse events during the collection process. 3…”

High-density microbioreactor process designed for automated point-of-care manufacturing of CAR T cells

“…The CAR T cells are then expanded to clinical dosages, which can take 7 to 14 days, before final formulation, cryopreservation and subsequent thawing for patient infusion 3,4 . Current commercial CAR T cell therapies largely rely on a centralized manufacturing model, but low manufacturing throughputs and long turnaround times of 21 to 37 days have hindered patient accessibility and treatment efficacy [4][5][6][7][8] . There is thus a need to intensify the scaling-out of autologous CAR T cell production, in order to reduce the wait times and cost of goods of these living drugs 3,9,10 .…”