The shifting roles and toxicities of cellular therapies in B‐cell malignancies

Abstract

Cellular therapies provide a curative‐intent option for patients with relapsedand refractory lymphomas. Current options including high dose chemotherapyfollowed by autologous or allogeneic hematopoietic stem cell transplantation or CD19 chimericantigen receptor T‐cell (CART) therapy. The indication varies according to lymphoma sub‐type and line oftherapy. The sequencing of these therapies and their use in second‐line orlater settings to manage these diseases is undergoing significant changes, withCD19 CAR T becoming a preferred option for relapsed aggressive B‐cell lymphoma.The mechanism of both therapies causes significant yet distinctlymphodepletion, infectious, and inflammatory toxicities. The resulting patternand timing of immune reconstitution helps guide risk‐mitigating strategies,revaccination, and infectious prophylaxis. In this review, we discuss theindication, efficacy, toxicity and immune reconstitution of autologoushematopoietic stem cell transplantation and CAR T therapy for use in thetreatment of lymphoma.

Car-T Cell Therapy in Large B Cell Lymphoma

“…CAR T cells can result in significant toxicities directly associated with the induction of powerful immune effector responses. Cytokine release syndrome (CRS), neurotoxicity, [71][72][73] or more rarely cardiotoxicity 74 represent the most frequent manifestations of this toxicity, which is in relationship with the immunological effects of CAR T cells. [71][72][73] Toxicities may be related both to the activation of T cells with the release of high levels of cytokines and the interaction between CAR and CAR-target antigens expressed on non-malignant cells.…”

“…Cytokine release syndrome (CRS), neurotoxicity, [71][72][73] or more rarely cardiotoxicity 74 represent the most frequent manifestations of this toxicity, which is in relationship with the immunological effects of CAR T cells. [71][72][73] Toxicities may be related both to the activation of T cells with the release of high levels of cytokines and the interaction between CAR and CAR-target antigens expressed on non-malignant cells. Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are well-known inflammatory side effects of CAR T-cell therapy.…”

“…Cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) are well-known inflammatory side effects of CAR T-cell therapy. [71][72][73] CRS typically presents with constitutional symptoms such as fever, myalgia, and arthralgia or constitutional symptoms such as rigors, fatigue, malaise, and anorexia. However, rapid progression to hemodynamic instability, respiratory failure, organ dysfunction, shock, and hemophagocytic lymphohistiocytosis has also been reported.…”

“…However, rapid progression to hemodynamic instability, respiratory failure, organ dysfunction, shock, and hemophagocytic lymphohistiocytosis has also been reported. 71,72 Depending on the product, CRS typically occurs within 1-2 weeks of CART-cell infusion but can occur as early as a few hours post-infusion. 71,72 CRS has a reported incidence between 37% and 93% across different studies.…”

“…71,72 Depending on the product, CRS typically occurs within 1-2 weeks of CART-cell infusion but can occur as early as a few hours post-infusion. 71,72 CRS has a reported incidence between 37% and 93% across different studies. Factors associated with CRS include the product type, tumor burden, disease indication, elevation in baseline inflammatory markers (i.e., ferritin, C-reactive protein), and concomitant infection.…”