Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T-cell therapy has changed the treatment landscape of B-cell non-Hodgkin lymphoma (NHL), especially for aggressive B-cell lymphomas.
CAR T-cell therapy is FDA approved for poor-risk diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL) when no other effective treatment options are available, and it has shown long-term remissions in up to 40% of patients without other treatment options.
CAR T-cell–related toxicities remain important potential complications of this therapy, which includes acute toxicity with cytokine-release syndrome and neurotoxicity, as well as long-term complications such as infection and cytopenias.
Relapse after CAR T-cell therapy remains a significant challenge and, although the exact mechanisms causing tumor escape remain unknown, relapse after CAR T-cell therapy that targets the CD19 antigen can be categorized broadly as (1) antigen loss, (2) lack of CAR T-cell persistence, or (3) host-specific factors.
Real-world analyses highlight that patient response rates and toxicity profiles were similar to the pivotal trials, while being inclusive of patients who would not fit within the highly restrictive parameters of clinical trials.
Trials are ongoing in multiple lymphoma histologies including T-cell lymphoma and Hodgkin lymphoma, in addition to novel autologous CAR constructs and allogeneic CAR T and natural killer (NK) cells.
For decades, the standard treatment for hematologic malignancies has been systemic chemotherapy, radiation, and stem cell transplantation (SCT). Exploiting the immune system to attack cancer cells is not a novel concept. In fact, the development of allogeneic stem cell transplantation (allo-HCT) first highlighted the potential of T-cells to eliminate cancer cells. As of this writing, immune effector cells, including T-cells and natural killer (NK) cells, which have been genetically engineered to express a chimeric antigen receptor (CAR), constitute a powerful new class of therapeutic agents to treat patients with hematologic malignancies, and have resulted in a paradigm shift in the treatment of relapsed lymphoma in particular. However, this emerging therapy also brings with it a different toxicity profile compared with chemotherapy and challenges in management related to cytokine-release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (Fig. 17–1). Adoptive cell therapy is FDA approved for the treatment of certain non-Hodgkin lymphoma (NHL) types, as well as B-cell acute lymphoblastic leukemia (ALL) and is currently being evaluated in clinical trials for follicular lymphoma (FL), marginal zone lymphoma (MZL), T-cell lymphoma (TCL), and Hodgkin lymphoma (HL). There are more than 750 cellular therapies in development, and approximately half of these are in clinical trials.1 This chapter will review current paradigms in cellular therapy for lymphoma.
Graphic representation of CAR T-cell therapy from screening to post-treatment assessment.
The concept of using CAR T-cells to target tumor surface antigens was described in the late 1980s, but first-generation CARs, which included only the receptor component CD3ζ as ...