CAR T-Cell Therapy

Abstract

The search for more effective and less toxic therapies for cancer has occupied scientists for decades. Recently approved treatments involving the genetic modification of a patient's own T cells to better target cancer cells are an important advance in cancer treatment, thereby sparing patients less effective therapies while offering a meaningful chance at remission. Chimeric antigen receptor (CAR) T cells involve the ex vivo transduction of T cells so they express a receptor on their surface that both is specific for a tumor antigen and contains T-cell activation domains such that engagement of the receptor by tumor antigen results in activation of the T cell against the tumor cell. The 2 approved CAR T-cell products include axicabtagene ciloleucel, manufactured by Kite Pharma, and tisagenlecleucel, a Novartis product. Both therapies target CD19 on the surface of B lymphocytes and are approved as single infusions for the treatment of relapsed and refractory B-cell malignancies, including B-cell acute lymphoblastic leukemia (B-ALL) in children and young adults (tisagenlecleucel) and aggressive B-cell non-Hodgkin lymphoma (B-NHL) (both tisagenlecleucel and axicabtagene ciloleucel). Even though these cell therapies produce durable remissions in some patients with no existing effective options, they are priced at a 1-time cost of $475 000 for B-ALL and $373 000 for B-NHL. Countries around the world are grappling with the cost of these treatments.CAR T-cell therapy is not the first treatment to present health care payers and policy makers with difficult choices about coverage and reimbursement; however, this treatment represents a significant escalation in these challenges. Ensuring equitable and affordable access to CAR T-cell therapy is an important policy goal; development of appropriate policies that anticipate and encourage similar innovations in the future is critical. As the largest payer for cancer care, Medicare is at the center of this discussion. CAR T-cell therapy can be used as a lens through which to examine the larger health policy challenges that high-cost innovation will bring to Medicare and, by extension, other payers.

Early toxicity and clinical outcomes after chimeric antigen receptor T-cell (CAR-T) therapy for lymphoma

“…[1][2][3][4][5] This is compounded by the common nature of immune-related toxicities, including cytokine release syndrome (CRS), neurotoxicity, and cardiotoxicity. [10][11][12][13] Yet, currently there is limited evidence to guide the prognostication of outcomes after treatment with CAR-T therapies.…”

Cost-effectiveness of Tisagenlecleucel vs Standard Care in High-risk Relapsed Pediatric Acute Lymphoblastic Leukemia in Canada

“…In the United States, while the Centers for Medicaid & Medicare and private insurers may place greater emphasis on efficacy over cost, the issue of drug affordability is nonetheless relevant as more expensive drug products like CAR T-cells are brought to market. 19,50…”

“…These results expand the evidence base for these decisions and underscore the allocative ethics that must be considered within a public insurer context. In the United States, while the Centers for Medicaid & Medicare and private insurers may place greater emphasis on efficacy over cost, the issue of drug affordability is nonetheless relevant as more expensive drug products like CAR T-cells are brought to market …”

Long‐lasting efficacy and safety of lenalidomide maintenance in patients with relapsed diffuse large B‐cell lymphoma who are not eligible for or failed autologous transplantation

“…These patients are good candidates for a few registered drugs, chimeric antigen receptor T (CAR-T) cells or prospective trials. However, only a small part of these patients has access to these therapies, 15 and only 22% of them enter prospective trials in large referral centers. 16,17 Therefore, use of improved schedule and combinations of available drugs is urgently needed to reduce mortality of patients with failed DLBCL.…”