Carfilzomib versus rituximab for treatment of de novo donor-specific antibodies in lung transplant recipients.

Autor: Razia D; Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, 500 W. Thomas Rd., Suite 500, Phoenix, AZ 85013, USA; Creighton University School of Medicine - Phoenix Regional Campus, 3100 N Central Ave, Phoenix, AZ 85012, USA. Electronic address: dr.deepikarazia@gmail.com., Hu C; Department of Epidemiology and Biostatistics, University of Arizona- Phoenix Campus, 550 E. Van Buren Street, UA Phoenix Plaza Building 1, Phoenix, AZ 85006, USA. Electronic address: hucc@arizona.edu., Cherrier L; Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, 500 W. Thomas Rd., Suite 500, Phoenix, AZ 85013, USA. Electronic address: Lauren.Cherrier@dignityhealth.org., Nasar A; Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, 500 W. Thomas Rd., Suite 500, Phoenix, AZ 85013, USA. Electronic address: aasya.nasar@commonspirit.org., Walia R; Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, 500 W. Thomas Rd., Suite 500, Phoenix, AZ 85013, USA; Creighton University School of Medicine - Phoenix Regional Campus, 3100 N Central Ave, Phoenix, AZ 85012, USA. Electronic address: rajat.walia@dignityhealth.org., Tokman S; Norton Thoracic Institute, St. Joseph's Hospital and Medical Center, 500 W. Thomas Rd., Suite 500, Phoenix, AZ 85013, USA; Creighton University School of Medicine - Phoenix Regional Campus, 3100 N Central Ave, Phoenix, AZ 85012, USA. Electronic address: sofya.tokman@commonspirit.org.
Jazyk: angličtina
Zdroj: Transplant immunology [Transpl Immunol] 2022 Dec; Vol. 75, pp. 101703. Date of Electronic Publication: 2022 Aug 30.
DOI: 10.1016/j.trim.2022.101703
Abstrakt: Introduction: De 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.
Methods: LTRs 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 FEV 1 6 months after treatment (ΔFEV 1 ).
Results: Forty-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 ΔFEV 1 at 6 months (p = 0.014).
Conclusion: Although both CFZ and RTX reduced the MFI of circulating DSAs, RTX prolonged the time to DSA rebound. Despite more pronounced improvement in FEV 1 with RTX, comparable CLAD-free survival between the 2 groups suggests that both drugs offer a reasonable treatment strategy for DSAs in LTRs.
Competing Interests: Declaration of Competing Interest The authors of this manuscript have no conflicts of interest to disclose. No outside funding was obtained for this study.
(Copyright © 2022 Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: