CTOTC‐08: A multicenter randomized controlled trial of rituximab induction to reduce antibody development and improve outcomes in pediatric lung transplant recipients

• Published in: American journal of transplantation Vol. 22; no. 1; pp. 230 - 244
• Main Authors: Sweet, Stuart C., Armstrong, Brian, Blatter, Joshua, Chin, Hyunsook, Conrad, Carol, Goldfarb, Samuel, Hayes, Don, Heeger, Peter S., Lyou, Victoria, Melicoff‐Portillo, Ernestina, Mohanakumar, Thalachallour, Odim, Jonah, Ravichandran, Ranjithkumar, Schecter, Marc, Storch, Gregory A., Visner, Gary, Williams, Nikki M., Danziger‐Isakov, Lara
• Format: Journal Article
• Language: English
• Published: United States Elsevier Limited 01.01.2022
• Subjects: alloantibody; Bronchiolitis obliterans; Bronchiolitis Obliterans - drug therapy; Bronchiolitis Obliterans - etiology; Bronchopneumonia; Child; Clinical trials; Flow cytometry; Globulins; Graft rejection; Graft Rejection - drug therapy; Graft Rejection - etiology; Graft Rejection - prevention & control; Histocompatibility antigen HLA; Humans; immunosuppressant ‐ fusion proteins and monoclonal antibodies: B cell specific; Immunosuppressive agents; immunosuppressive regimens ‐ induction; Immunotherapy; Lung; lung (allograft) function/dysfunction; Lung transplantation; Lung Transplantation - adverse effects; lung transplantation/pulmonology; Lung transplants; Lymphocytes; Monoclonal antibodies; Obliterative bronchiolitis; Pediatrics; Peripheral blood; Placebos; Rituximab; translational research/science; Transplant Recipients; Xenografts; lung (allograft) function/dysfunction; translational research/science; immunosuppressant - fusion proteins and monoclonal antibodies: B cell specific; immunosuppressive regimens - induction; lung transplantation/pulmonology; pediatrics; alloantibody
• ISSN: 1600-6135; 1600-6143; 1600-6143
• DOI: 10.1111/ajt.16862

We conducted a randomized, placebo‐controlled, double‐blind study of pediatric lung transplant recipients, hypothesizing that rituximab plus rabbit anti‐thymocyte globulin induction would reduce de novo donor‐specific human leukocyte antigen antibodies (DSA) development and improve outcomes. We serially obtained clinical data, blood, and respiratory samples for at least one year posttransplant. We analyzed peripheral blood lymphocytes by flow cytometry, serum for antibody development, and respiratory samples for viral infections using multiplex PCR. Of 45 subjects enrolled, 34 were transplanted and 27 randomized to rituximab (n = 15) or placebo (n = 12). No rituximab‐treated subjects versus five placebo‐treated subjects developed de novo DSA with mean fluorescence intensity >2000. There was no difference between treatment groups in time to the primary composite outcome endpoint (death, bronchiolitis obliterans syndrome [BOS] grade 0‐p, obliterative bronchiolitis or listing for retransplant). A post‐hoc analysis substituting more stringent chronic lung allograft dysfunction criteria for BOS 0‐p showed no difference in outcome (p = .118). The incidence of adverse events including infection and rejection episodes was no different between treatment groups. Although the study was underpowered, we conclude that rituximab induction may have prevented early DSA development in pediatric lung transplant recipients without adverse effects and may improve outcomes (Clinical Trials: NCT02266888). A multicenter randomized controlled trial in pediatric lung transplantation shows that Rituximab induction reduces the development of de novo donor specific antibody.