Understanding and Managing Large B Cell Lymphoma Relapses after Chimeric Antigen Receptor T Cell Therapy

• Published in: Biology of blood and marrow transplantation 2019-11, Vol.25 (11), p.e344-e351
• Main Authors: Byrne, Michael, Oluwole, Olalekan O., Savani, Bipin, Majhail, Navneet S., Hill, Brian T., Locke, Fredrick L.
• Format: Article
• Language: English
• Subjects: Antigens, CD19 - therapeutic use; CAR T cell; Diffuse large B cell lymphoma; Humans; Immunotherapy, Adoptive; Lymphoma, Large B-Cell, Diffuse - immunology; Lymphoma, Large B-Cell, Diffuse - pathology; Lymphoma, Large B-Cell, Diffuse - therapy; Receptors, Antigen, T-Cell - therapeutic use; Recurrence; Relapse
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2019.06.036

•CD19 chimeric antigen receptor (CAR) T cell therapy can achieve durable remissions for patients with relapsed/refractory diffuse large B cell lymphoma, yet approximately 60% of patients will relapse.•Patients who progress after CAR T therapy, or those with stable disease at 3 months, are at risk for poor clinical outcomes. Future efforts are needed to improve the outcomes of these patients.•To ensure success of future strategies, such as novel CAR T cell constructs or combination therapies, a better understanding of the mechanisms of disease resistance is necessary. Most patients with large cell lymphoma are cured with frontline chemoimmunotherapy. For individuals with refractory disease and those who relapse after conventional therapies, chimeric antigen receptor (CAR) T cells are an important treatment option and have led to remissions in otherwise refractory patients. In the pivotal trials, durable responses were achieved in approximately 40% to 50% of patients treated with axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel, indicating that many patients will require subsequent treatment. Failure after CAR T cell therapy is caused by a variety of factors that can be divided into 3 broad categories: tumor intrinsic factors, other host factors, and inadequacies of the CAR T cells. Within this framework, this article reviews possible mechanisms of treatment failures and, based on the timing of relapse, considers potential salvage therapies and opportunities for future clinical studies.