ABSTRACT
BACKGROUND: Anti-CD19 chimeric antigen receptor T-cell immunotherapy (CAR-T) is now a standard treatment of relapsed or refractory B-cell non-Hodgkin lymphomas; however, a significant portion of patients do not respond to CAR-T and/or experience toxicities. Lymphodepleting chemotherapy is a critical component of CAR-T that enhances CAR-T-cell engraftment, expansion, cytotoxicity, and persistence. We hypothesized that the lymphodepletion regimen might affect the safety and efficacy of CAR-T. PATIENTS AND METHODS: We compared the safety and efficacy of lymphodepletion using either fludarabine/cyclophosphamide (n = 42) or bendamustine (n = 90) before tisagenlecleucel in two cohorts of patients with relapsed or refractory large B-cell lymphomas treated consecutively at three academic institutions in the United States (University of Pennsylvania, n = 90; Oregon Health & Science University, n = 35) and Europe (University of Vienna, n = 7). Response was assessed using the Lugano 2014 criteria and toxicities were assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and, when possible, the American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading. RESULTS: Fludarabine/cyclophosphamide led to more profound lymphocytopenia after tisagenlecleucel infusion compared with bendamustine, although the efficacy of tisagenlecleucel was similar between the two groups. We observed significant differences, however, in the frequency and severity of adverse events. In particular, patients treated with bendamustine had lower rates of cytokine release syndrome and neurotoxicity. In addition, higher rates of hematological toxicities were observed in patients receiving fludarabine/cyclophosphamide. Bendamustine-treated patients had higher nadir neutrophil counts, hemoglobin levels, and platelet counts, as well as a shorter time to blood count recovery, and received fewer platelet and red cell transfusions. Fewer episodes of infection, neutropenic fever, and post-infusion hospitalization were observed in the bendamustine cohort compared with patients receiving fludarabine/cyclophosphamide. CONCLUSIONS: Bendamustine for lymphodepletion before tisagenlecleucel has efficacy similar to fludarabine/cyclophosphamide with reduced toxicities, including cytokine release syndrome, neurotoxicity, infectious and hematological toxicities, as well as reduced hospital utilization.
Subject(s)
Bendamustine Hydrochloride , Immunotherapy, Adoptive , Lymphocyte Depletion , Lymphoma, Large B-Cell, Diffuse , Receptors, Antigen, T-Cell , Bendamustine Hydrochloride/adverse effects , Bendamustine Hydrochloride/therapeutic use , Cyclophosphamide/therapeutic use , Cytokine Release Syndrome/drug therapy , Humans , Immunotherapy, Adoptive/methods , Lymphocyte Depletion/methods , Lymphoma, Large B-Cell, Diffuse/therapy , Receptors, Antigen, T-Cell/therapeutic useABSTRACT
At the University of Alabama Hospitals, we have established a protocol of routine and supplementary projections to provide an unusually thorough and complete evaluation of the patient suspected of harboring certain acute cervical spine injuries. This paper reports an evaluation of a protocol designed for use in the radiographic emergency room. The protocol was designed to provide uniform roentgen assessment of the cervical spine with a minimum number of exposures, ease in radiographing the patient, and strict avoidance of manipulation of the patient. A total of 268 patients were evaluated. Of these patients, 98 (thirty-six per cent) were admitted to the hospital for various reasons and none required additional roentgenograms of the cervical spine for better delineation. In addition, in no instance was a previously undiagnosed cervical spine injury later found.