ABSTRACT
Chimeric antigen receptor (CAR) T-cell therapies that specifically target the CD19 antigen have emerged as a highly effective treatment option in patients with refractory B-cell hematological malignancies. Safety and efficacy outcomes from the pivotal prospective clinical trials of axicabtagene ciloleucel, tisagenlecleucel and lisocabtagene maraleucel and the retrospective, postmarketing, real-world analyses have confirmed high response rates and durable remissions in patients who had failed multiple lines of therapy and had no meaningful treatment options. Although initially administered in the inpatient setting, there has been a growing interest in delivering CAR-T cell therapy in the outpatient setting; however, this has not been adopted as standard clinical practice for multiple reasons, including logistic and reimbursement issues. CAR-T cell therapy requires a multidisciplinary approach and coordination, particularly if given in an outpatient setting. The ability to monitor patients closely is necessary and proper protocols must be established to respond to clinical changes to ensure efficient, effective and rapid evaluation either in the clinic or emergency department for management decisions regarding fever, sepsis, cytokine release syndrome and neurological events, specifically immune effector cell-associated neurotoxicity syndrome. This review presents the authors' institutional experience with the preparation and delivery of outpatient CD19-directed CAR-T cell therapy.
Subject(s)
Ambulatory Care , Antigens, CD19/immunology , Immunotherapy, Adoptive , Lymphoma, B-Cell/therapy , Precursor Cell Lymphoblastic Leukemia-Lymphoma/therapy , Receptors, Chimeric Antigen/genetics , T-Lymphocytes/transplantation , Ambulatory Care/economics , Cost-Benefit Analysis , Hospital Costs , Humans , Immunotherapy, Adoptive/adverse effects , Immunotherapy, Adoptive/economics , Immunotherapy, Adoptive/mortality , Lymphoma, B-Cell/economics , Lymphoma, B-Cell/immunology , Lymphoma, B-Cell/mortality , Patient Safety , Precursor Cell Lymphoblastic Leukemia-Lymphoma/economics , Precursor Cell Lymphoblastic Leukemia-Lymphoma/immunology , Precursor Cell Lymphoblastic Leukemia-Lymphoma/mortality , Risk Assessment , Risk Factors , T-Lymphocytes/immunology , Treatment OutcomeABSTRACT
The SARS-CoV-2 coronavirus (COVID-19) pandemic has significantly impacted the delivery of cellular therapeutics, including chimeric antigen receptor (CAR) T cells. This impact has extended beyond patient care to include logistics, administration, and distribution of increasingly limited health care resources. Based on the collective experience of the CAR T-cell Consortium investigators, we review and address several questions and concerns regarding cellular therapy administration in the setting of COVID-19 and make general recommendations to address these issues. Specifically, we address (1) necessary resources for safe administration of cell therapies; (2) determinants of cell therapy utilization; (3) selection among patients with B cell non-Hodgkin lymphomas and B cell acute lymphoblastic leukemia; (4) supportive measures during cell therapy administration; (5) use and prioritization of tocilizumab; and (6) collaborative care with referring physicians. These recommendations were carefully formulated with the understanding that resource allocation is of the utmost importance, and that the decision to proceed with CAR T cell therapy will require extensive discussion of potential risks and benefits. Although these recommendations are fluid, at this time it is our opinion that the COVID-19 pandemic should not serve as reason to defer CAR T cell therapy for patients truly in need of a potentially curative therapy.