Improving access to chimeric antigen receptor T-cells for refractory or relapsing diffuse large B cell lymphoma therapy in Asia

Abstract

Chimeric antigen receptor T-cell (CAR-T)-mediated therapies have shown promising clinical benefit in patients with refractory or relapsing (R/R) diffuse large B-cell lymphoma (DLBCL). However, CAR-T treatment presents challenges such as lack of drug accessibility, financial barriers, variable physician preference or experience, and risk assessment based on patient-specific characteristics. This article thus aims to provide an overview of the CAR-T landscape for R/R DLBCL in Asia, with a focus on identifying barriers to access, from the perspective of Asian and international lymphoma experts. Presently, existing clinical data indicate that CAR-T therapy is a potentially curative strategy for R/R DLBCL in addition to stem cell transplantation, provided the patient's disease profile and treatment history have been thoroughly considered. However, longer-term follow-up data from large-scale studies are needed to confirm curative potential and define optimal sequencing of CAR-T in the context of novel emerging treatments, such as bi-specific antibodies, in the management of R/R DLBCL. Consequently, further research into CAR-T would benefit from collaboration between institutions. Furthermore, there is a wide disparity in CAR-T accessibility across regions due to complicated logistics and cost, which represent a significant barrier to patients in Asia. Hence, there is a need to increase representation and engagement across different stakeholders such as policymakers, payers, and the industry to arrive at a consensus on patient selection, establish clear guidelines, and develop strategies to lower CAR-T costs. Ultimately, data can support a multi-stakeholder approach when devising strategies to make CAR-T feasible and sustainable for patients.

Keywords: CAR-T; Diffuse large B-cell lymphoma; Immunotherapy; Lymphoma; Novel therapy.

Fig. 1

Summary of barriers to CAR-T treatment in Asia and potential solutions. The figure presents a visual summary of barriers to CAR-T treatment in Asia and potential solutions. Moving from the left to the right of the figure, each point is presented in a rectangle box to show how challenges map on to action points for evidence-generating activities, and how these data can be used to encourage policymakers and payers to bridge the financial gap between patients and CAR-T. On the far left-hand side, there are three boxes that summarise the challenges of CAR-T treatment in Asia, such as how: 1. specific patient/disease characteristics may be associated with poor response and outcomes with CAR-T, 2. long-term benefits of CAR-T need to be balanced against the risk of adverse events, and 3. despite funding assistance, the cost of CAR-T remains as a barrier to receiving treatment. These challenges link to two boxes on the right, which show the ways that these challenges can be collectively addressed, specifically by: 1. generating longer-term data on outcomes of CAR-T and bispecific antibodies, and 2. collaboration between institutions to share learnings and research. This continues on to two boxes on the further right, which show the collective practical applications and outputs of these learnings and data, specifically to: 1. develop guidelines for patient selection and optimal sequencing of CAR-T, and 2. conduct cost-effectiveness assessments. Finally, the box on the extreme right concludes that: evidence can be used to encourage policymakers and payers to bridge the financial gap between patients and CAR-T. CAR-T chimeric antigen receptor T-cell