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Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY Starling, R. C., Armstrong, B., Bridges, N. D., Eisen, H., Givertz, M. M., Kfoury, A. G., Kobashigawa, J., Ikle, D., Morrison, Y., Pinney, S., Stehlik, J., Tripathi, S., Sayegh, M. H., Chandraker, A., Gus, B., Keslar, K., Magyar, B., Petrich, J., Starling, R. C., Tang, W., Brooks, K., Givertz, M., Kelly, C., Klein, K., Crisalli, K., DeBronkart, S., Madsen, J., Semigran, M., Vetrano, J., DeMarco, T., Fields, S., Maguire, C., Gordon, R., Anderson, A., Regalado, J., Warzecha, A., Goldberg, L., Olt, C., Rockwell, K., Harris, A., Johnson, M., Johnston, S., Roginski, C., Ahmed, R., Cohen, I., Peace, D., Pinney, S., Yao, T., Araujo, G., Bhimaraj, A., Karanga, E., Patel, V., Chait, J., Deng, M., Fonarow, G., Shin, C., Gibbs, C., Hunt, J., Johnson, M., Worley, T., Gibbs, J., Kirk, J., Redd, W., Stehlik, J., Bryan, J., French, A., Kfoury, A. G., Konery, K., Feller, E., Lee, M., Pierson, R., Young, C., Hollifield, T., Porter, K., Schulz, M., VanBakel, A., Khush, K., Luikart, H., Son Nguyen, Pham, M., DeNofrio, D., O'Kelly, R., Garcia, L., Kobashigawa, J., Sana, S., Starks, B., Thottam, M., Yi, A., Cabuay, B., Olson, R., Tucker, L., Uppgaard, L., Eisen, H., Lai, D., Poisker, C., Dragicevic, K., Kelner, H., Luke, D., Nelson, J., Raveendran, G., Kleissas, N., Murali, S., Rayl, K., Sherry, S., Cosgrove, M., CTOT-11 Study Investigators 2019; 74 (1): 36–51

Abstract

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.The study sought to determine whether B cell depletion therapy would attenuate the development of cardiac allograft vasculopathy.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.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.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).

View details for DOI 10.1016/j.jacc.2019.04.056

View details for Web of Science ID 000473259200007

View details for PubMedID 31272550