The acceleration of CAR‐T therapy in non‐Hodgkin lymphoma

Abstract

Recent advances in diffuse large B‐cell lymphomas have included both identification of high‐risk subtypes characterized by multiply relapsed and/or refractory disease as well as novel treatment in the form of cellular therapy. Chimeric antigen receptor (CAR)‐T cell therapy is a recently developed approach to address the poor outcomes in this patient population. The CAR‐T cell construct has evolved although several iterations as it transitioned from the lab to the clinic. Three major studies have evaluated the efficacy of CD19‐directed CAR‐T cell therapy in aggressive B‐cell non‐Hodgkin lymphoma; each demonstrating durable complete remissions in heavily pretreated patients. The cost of this remarkable therapy, however, includes cytokine release syndrome and neurotoxicity shortly after administration as well as delayed infectious complications due to B‐cell aplasia. Future investigations are focused on the optimizing both safety and efficacy of CAR‐T cell therapy.

CD19-Targeted Chimeric Antigen Receptor T-cell Therapy for Concomitant Diffuse Large B-cell Lymphoma and Multiple Myeloma

“…CD19-targeted CAR T-cell therapy has become an established and accepted standard of care for multiply r/r DLBCL when it is available [ 15 ]. However, the role of HSCT in r/r DLBCL is as the standard of care after second-line salvage [ 16 ].…”

The novel CD19-targeting antibody-drug conjugate huB4-DGN462 shows improved anti-tumor activity compared to SAR3419 in CD19-positive lymphoma and leukemia models

“…36 Despite the success of CD19-targeting immunotherapies, there still remains the need for more effective therapies, particularly in patients with relapsed/refractory lymphomas such as DLBCL. The clinical activity of CD19-targeting ADC following other anti-CD19 directed therapeutic modalities 32–39 will have to be determined. However, unlike immunotherapies that stimulate the patient’s immune systems to fight cancer, ADC like huB4-DGN462 kill tumor cells by delivering a cytotoxic payload directly to tumor cells.…”

Emerging Therapies for the Treatment of Relapsed or Refractory Diffuse Large B Cell Lymphoma

“…Importantly, a number of logistical and practical barriers must be overcome before this costly therapy can be routinely offered in Canada. Currently, car-t therapy is manufactured in a centralized system in the United States, with production taking an average of 10-21 days 71 . Subsequently, the product has to be shipped through Canadian customs to reach infusion centres.…”