Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation

CTOT-11 Study Investigators

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Background: The CTOT-11 (Prevention of Cardiac Allograft Vasculopathy Using Rituximab Therapy in Cardiac Transplantation [Clinical Trials in Organ Transplantation-11]) study was a randomized, placebo-controlled, multicenter, double-blinded clinical trial in nonsensitized primary heart transplant (HTX) recipients. Objectives: The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. Methods: A total of 163 HTX recipients were randomized to rituximab 1,000 mg intravenous or placebo on days 0 and 12 post-transplant. Primary outcome was change in percent atheroma volume (PAV) from baseline to 1 year measured by intravascular ultrasound. Secondary outcomes included treated episodes of acute rejection, de novo anti-HLA antibodies (including donor-specific antibodies), and phenotypic differentiation of B cells. Results: There were no significant differences at study entry between the rituximab and placebo groups. Paired intravascular ultrasound measures were available at baseline and 1 year in 86 subjects (49 rituximab, 37 placebo). The mean ± SD change in PAV at 12 months was +6.8 ± 8.2% rituximab versus +1.9 ± 4.4% placebo (p = 0.0019). Mortality at 12 months was 3.4% rituximab versus 6.8% placebo (p = 0.47); there were no retransplants or post-transplant lymphoproliferative disorder. The rate of treated rejection was 24.7% rituximab versus 32.4% placebo (p = 0.28). Rituximab therapy effectively eliminated CD20+/CD19+ B cells followed by a gradual expansion of a CD19 cell population in the rituximab-treated group. Conclusions: A marked, unexpected increase in coronary artery PAV with rituximab was observed during the first year in HTX recipients. One-year mortality was not impacted; however, longer-term follow-up and mechanistic explanations are required. (Prevention of Cardiac Allograft Vasculopathy Using Rituximab [Rituxan] Therapy in Cardiac Transplantation; NCT01278745)

Original languageEnglish (US)
Pages (from-to)36-51
Number of pages16
JournalJournal of the American College of Cardiology
Volume74
Issue number1
DOIs
StatePublished - Jul 9 2019

Fingerprint

Heart Transplantation
Allografts
Placebos
Atherosclerotic Plaques
B-Lymphocytes
Rituximab
Clinical Trials
Transplants
Lymphoproliferative Disorders
Mortality
Organ Transplantation
Cell- and Tissue-Based Therapy
Anti-Idiotypic Antibodies
Coronary Vessels
Therapeutics
Tissue Donors

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

@article{013190a132024232941eae3602273c74,
title = "Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation",
abstract = "Background: The CTOT-11 (Prevention of Cardiac Allograft Vasculopathy Using Rituximab Therapy in Cardiac Transplantation [Clinical Trials in Organ Transplantation-11]) study was a randomized, placebo-controlled, multicenter, double-blinded clinical trial in nonsensitized primary heart transplant (HTX) recipients. Objectives: The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. Methods: A total of 163 HTX recipients were randomized to rituximab 1,000 mg intravenous or placebo on days 0 and 12 post-transplant. Primary outcome was change in percent atheroma volume (PAV) from baseline to 1 year measured by intravascular ultrasound. Secondary outcomes included treated episodes of acute rejection, de novo anti-HLA antibodies (including donor-specific antibodies), and phenotypic differentiation of B cells. Results: There were no significant differences at study entry between the rituximab and placebo groups. Paired intravascular ultrasound measures were available at baseline and 1 year in 86 subjects (49 rituximab, 37 placebo). The mean ± SD change in PAV at 12 months was +6.8 ± 8.2{\%} rituximab versus +1.9 ± 4.4{\%} placebo (p = 0.0019). Mortality at 12 months was 3.4{\%} rituximab versus 6.8{\%} placebo (p = 0.47); there were no retransplants or post-transplant lymphoproliferative disorder. The rate of treated rejection was 24.7{\%} rituximab versus 32.4{\%} placebo (p = 0.28). Rituximab therapy effectively eliminated CD20+/CD19+ B cells followed by a gradual expansion of a CD19– cell population in the rituximab-treated group. Conclusions: A marked, unexpected increase in coronary artery PAV with rituximab was observed during the first year in HTX recipients. One-year mortality was not impacted; however, longer-term follow-up and mechanistic explanations are required. (Prevention of Cardiac Allograft Vasculopathy Using Rituximab [Rituxan] Therapy in Cardiac Transplantation; NCT01278745)",
author = "{CTOT-11 Study Investigators} and Starling, {Randall C.} and Brian Armstrong and Bridges, {Nancy D.} and Howard Eisen and Givertz, {Michael M.} and Kfoury, {Abdallah G.} and Jon Kobashigawa and David Ikle and Yvonne Morrison and Sean Pinney and Josef Stehlik and Sudipta Tripathi and Sayegh, {Mohamed H.} and Anil Chandraker and Barbara Gus and Karen Keslar and Bill Magyar and John Petrich and Tang, {W. H.Wilson} and Kimberly Brooks and Michael Givertz and Charles Kelly and Katie Klein and Kerry Crisalli and Sandra DeBronkart and Joren Madsen and Marc Semigran and John Vetrano and Teresa DeMarco and Scott Fields and Carol Maguire and Robert Gordon and Allen Anderson and Jane Regalado and Anna Warzecha and Lee Goldberg and Caroline Olt and Kenneth Rockwell and Ashley Harris and Maryl Johnson and Susan Johnston and Chris Roginski and Rashid Ahmed and Ivy Cohen and Denise Peace and Tina Yao and Gloria Araujo and Arvind Bhimaraj and Eunice Karanga and Varsha Patel",
year = "2019",
month = "7",
day = "9",
doi = "10.1016/j.jacc.2019.04.056",
language = "English (US)",
volume = "74",
pages = "36--51",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "1",

}

Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation. / CTOT-11 Study Investigators.

In: Journal of the American College of Cardiology, Vol. 74, No. 1, 09.07.2019, p. 36-51.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation

AU - CTOT-11 Study Investigators

AU - Starling, Randall C.

AU - Armstrong, Brian

AU - Bridges, Nancy D.

AU - Eisen, Howard

AU - Givertz, Michael M.

AU - Kfoury, Abdallah G.

AU - Kobashigawa, Jon

AU - Ikle, David

AU - Morrison, Yvonne

AU - Pinney, Sean

AU - Stehlik, Josef

AU - Tripathi, Sudipta

AU - Sayegh, Mohamed H.

AU - Chandraker, Anil

AU - Gus, Barbara

AU - Keslar, Karen

AU - Magyar, Bill

AU - Petrich, John

AU - Tang, W. H.Wilson

AU - Brooks, Kimberly

AU - Givertz, Michael

AU - Kelly, Charles

AU - Klein, Katie

AU - Crisalli, Kerry

AU - DeBronkart, Sandra

AU - Madsen, Joren

AU - Semigran, Marc

AU - Vetrano, John

AU - DeMarco, Teresa

AU - Fields, Scott

AU - Maguire, Carol

AU - Gordon, Robert

AU - Anderson, Allen

AU - Regalado, Jane

AU - Warzecha, Anna

AU - Goldberg, Lee

AU - Olt, Caroline

AU - Rockwell, Kenneth

AU - Harris, Ashley

AU - Johnson, Maryl

AU - Johnston, Susan

AU - Roginski, Chris

AU - Ahmed, Rashid

AU - Cohen, Ivy

AU - Peace, Denise

AU - Yao, Tina

AU - Araujo, Gloria

AU - Bhimaraj, Arvind

AU - Karanga, Eunice

AU - Patel, Varsha

PY - 2019/7/9

Y1 - 2019/7/9

N2 - Background: The CTOT-11 (Prevention of Cardiac Allograft Vasculopathy Using Rituximab Therapy in Cardiac Transplantation [Clinical Trials in Organ Transplantation-11]) study was a randomized, placebo-controlled, multicenter, double-blinded clinical trial in nonsensitized primary heart transplant (HTX) recipients. Objectives: The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. Methods: A total of 163 HTX recipients were randomized to rituximab 1,000 mg intravenous or placebo on days 0 and 12 post-transplant. Primary outcome was change in percent atheroma volume (PAV) from baseline to 1 year measured by intravascular ultrasound. Secondary outcomes included treated episodes of acute rejection, de novo anti-HLA antibodies (including donor-specific antibodies), and phenotypic differentiation of B cells. Results: There were no significant differences at study entry between the rituximab and placebo groups. Paired intravascular ultrasound measures were available at baseline and 1 year in 86 subjects (49 rituximab, 37 placebo). The mean ± SD change in PAV at 12 months was +6.8 ± 8.2% rituximab versus +1.9 ± 4.4% placebo (p = 0.0019). Mortality at 12 months was 3.4% rituximab versus 6.8% placebo (p = 0.47); there were no retransplants or post-transplant lymphoproliferative disorder. The rate of treated rejection was 24.7% rituximab versus 32.4% placebo (p = 0.28). Rituximab therapy effectively eliminated CD20+/CD19+ B cells followed by a gradual expansion of a CD19– cell population in the rituximab-treated group. Conclusions: A marked, unexpected increase in coronary artery PAV with rituximab was observed during the first year in HTX recipients. One-year mortality was not impacted; however, longer-term follow-up and mechanistic explanations are required. (Prevention of Cardiac Allograft Vasculopathy Using Rituximab [Rituxan] Therapy in Cardiac Transplantation; NCT01278745)

AB - Background: The CTOT-11 (Prevention of Cardiac Allograft Vasculopathy Using Rituximab Therapy in Cardiac Transplantation [Clinical Trials in Organ Transplantation-11]) study was a randomized, placebo-controlled, multicenter, double-blinded clinical trial in nonsensitized primary heart transplant (HTX) recipients. Objectives: The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy. Methods: A total of 163 HTX recipients were randomized to rituximab 1,000 mg intravenous or placebo on days 0 and 12 post-transplant. Primary outcome was change in percent atheroma volume (PAV) from baseline to 1 year measured by intravascular ultrasound. Secondary outcomes included treated episodes of acute rejection, de novo anti-HLA antibodies (including donor-specific antibodies), and phenotypic differentiation of B cells. Results: There were no significant differences at study entry between the rituximab and placebo groups. Paired intravascular ultrasound measures were available at baseline and 1 year in 86 subjects (49 rituximab, 37 placebo). The mean ± SD change in PAV at 12 months was +6.8 ± 8.2% rituximab versus +1.9 ± 4.4% placebo (p = 0.0019). Mortality at 12 months was 3.4% rituximab versus 6.8% placebo (p = 0.47); there were no retransplants or post-transplant lymphoproliferative disorder. The rate of treated rejection was 24.7% rituximab versus 32.4% placebo (p = 0.28). Rituximab therapy effectively eliminated CD20+/CD19+ B cells followed by a gradual expansion of a CD19– cell population in the rituximab-treated group. Conclusions: A marked, unexpected increase in coronary artery PAV with rituximab was observed during the first year in HTX recipients. One-year mortality was not impacted; however, longer-term follow-up and mechanistic explanations are required. (Prevention of Cardiac Allograft Vasculopathy Using Rituximab [Rituxan] Therapy in Cardiac Transplantation; NCT01278745)

UR - http://www.scopus.com/inward/record.url?scp=85067796926&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85067796926&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2019.04.056

DO - 10.1016/j.jacc.2019.04.056

M3 - Article

C2 - 31272550

AN - SCOPUS:85067796926

VL - 74

SP - 36

EP - 51

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 1

ER -