Carfilzomib versus rituximab for treatment of de novo donor-specific antibodies in lung transplant recipients |
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| Institution: | 1. Norton Thoracic Institute, St. Joseph''s Hospital and Medical Center, 500 W. Thomas Rd., Suite 500, Phoenix, AZ 85013, USA;2. Department of Epidemiology and Biostatistics, University of Arizona- Phoenix Campus, 550 E. Van Buren Street, UA Phoenix Plaza Building 1, Phoenix, AZ 85006, USA;3. Creighton University School of Medicine – Phoenix Regional Campus, 3100 N Central Ave, Phoenix, AZ 85012, USA;1. Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Nagasaki University Graduate School of Biomedical Science, Nagasaki, Japan;2. Department of Hematology, Sasebo City General Hospital, Sasebo, Japan;3. Department of Hematology, Nagasaki University Hospital, Nagasaki, Japan;4. Department of Hematology, National Hospital Organization Nagasaki Medical Center, Omura, Japan;5. Department of Hematology, Atomic Bomb Disease and Hibakusha Medicine Unit, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan;6. Department of Hematology, Japanese Red Cross Nagasaki Genbaku Hospital, Nagasaki, Japan;1. Neurological Surgery Department, University of São Paulo, School of Medicine, São Paulo, Brazil;2. Organ Procurement Organization, Hospital das Clínicas, University of São Paulo, School of Medicine, São Paulo, Brazil;3. Gastroenterology Department, University of São Paulo, School of Medicine, São Paulo, Brazil;4. Medical Science Department, Nove de Julho University, São Paulo, Brazil;5. Cardiopneumology Department, University of São Paulo, School of Medicine, São Paulo, Brazil;6. School of Nursing of the University of São Paulo, São Paulo, Brazil;1. Division of Hematology with BMT, A.O.U. “Policlinico-San Marco”, Via S. Sofia 78, 95123 Catania, Italy;2. Onco-Hematology and BMT Unit, “Mediterranean Institute of Oncology”, Viagrande, Italy;3. Division of Nephrology, A.O.U. Policlinico “G. Rodolico-San Marco”, Catania, Italy;1. Department of Renal Surgery and Transplantation, Jichi Medical University Hospital, Tochigi, Japan;2. Department of Orthopaedics, Teikyo University School of Medicine, Tokyo, Japan;3. Oku medical clinic, Osaka, Japan;4. Scientific Research WorkS Peer Support Group (SRWS-PSG), Osaka, Japan;1. Department of Neurology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250031, China;2. Department of Psychology, Central Hospital Affiliated to Shandong First Medical University, Jinan, Shandong 250031, China;3. Department of Neurology, Shandong Provincial Third Hospital, Shandong University, Jinan, Shandong 250031, China;1. Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA, USA;2. Starzl Transplantation Institute, Department of Surgery, University of Pittsburgh, Pittsburgh, PA, USA;3. Division of Plastic Surgery and Hand Surgery, University Hospital Zurich, Zurich, ZH, Switzerland;4. th;5. Department of Surgery, Uniformed Service University of the Health Sciences, Bethesda, MD, USA;6. Department of Pathology, University of Pittsburgh, Pittsburgh, PA, USA;7. Wake Forest Institute for Regenerative Medicine, Wake Forest University, Winston-Salem, NC, USA;8. Division of Plastic Surgery, Department of Surgery, University of Colorado, Denver, CO, USA;9. Department of Immunology, University of Pittsburgh, Pittsburgh, PA, USA |
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| Abstract: | IntroductionDe novo donor-specific antibodies (DSAs) increase the risk of chronic lung allograft dysfunction (CLAD) in lung transplant recipients (LTRs). Both carfilzomib (CFZ) and rituximab (RTX) lower the mean fluorescent intensity (MFI) of DSAs, but comparative data are lacking. We compared CLAD-free survival and the degree and duration of DSA depletion after treatment of LTRs with CFZ or RTX.MethodsLTRs that received CFZ or RTX for DSA depletion between 08/01/2015 and 08/31/2020 were included. The primary outcome was CLAD-free survival. Secondary outcomes were change in MFI at corresponding loci within 6 months of treatment (ΔMFI), time to DSA rebound, and change in % predicted FEV1 6 months after treatment (ΔFEV1).ResultsForty-four LTRs were identified, 7 of whom had ≥2 drug events; therefore, 53 drug events were divided into 2 groups, CFZ (n = 17) and RTX (n = 36). Use of plasmapheresis, immunoglobulin, and mycophenolate augmentation was equivalent in both groups. CLAD-free survival with a single RTX event was superior to that after ≥2 drug events (p = 0.001) but comparable to that with a single CFZ event (p = 0.399). Both drugs significantly lowered the MFI at DQ locus, and the median ΔMFI was comparable. Compared to the RTX group, the CFZ group had a shorter median interval to DSA rebound (p = 0.015) and a lower ΔFEV1 at 6 months (p = 0.014).ConclusionAlthough both CFZ and RTX reduced the MFI of circulating DSAs, RTX prolonged the time to DSA rebound. Despite more pronounced improvement in FEV1 with RTX, comparable CLAD-free survival between the 2 groups suggests that both drugs offer a reasonable treatment strategy for DSAs in LTRs. |
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