Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors before and after Allogeneic Transplantation

• Published in: Biology of blood and marrow transplantation 2019-01, Vol.25 (1), p.94-99
• Main Authors: Ijaz, Awais, Khan, Ali Younas, Malik, Saad Ullah, Faridi, Warda, Fraz, Muhammad Asad, Usman, Muhammad, Tariq, Muhammad Junaid, Durer, Seren, Durer, Ceren, Russ, Atlantis, Parr, Nadia Nunes Cavalcante, Baig, Zeeshan, Sagar, FNU, Ali, Zeeshan, McBride, Ali, Anwer, Faiz
• Format: Article
• Language: English
• Subjects: Allogeneic hematopoietic stem cell transplantation; Antibodies, Monoclonal, Humanized - therapeutic use; Antineoplastic Agents, Immunological - therapeutic use; Chronic Disease; Disease-Free Survival; Female; Graft vs Host Disease - mortality; Graft vs Host Disease - prevention & control; Graft-versus-host disease; Hematologic Neoplasms - mortality; Hematologic Neoplasms - therapy; Hematopoietic Stem Cell Transplantation; Humans; Ipilimumab; Male; Nivolumab; Outcomes; Pembrolizumab; Risk Factors; Survival Rate; Transplantation, Homologous
• ISSN: 1083-8791; 1523-6536
• DOI: 10.1016/j.bbmt.2018.08.028

•The use of checkpoint inhibitors (CPIs) in hematologic malignancies before allogeneic hematopoietic stem cell transplantation (allo-HSCT) is associated with high rates of hyperacute (7%), acute (56%), and chronic (29%) graft-versus-host disease (GVHD).•The use of CPIs in hematologic malignancies after allo-HSCT shows high efficacy but also increases the risk of GVHD (14% acute, 9% chronic). Investigators are using checkpoint inhibitors (CPIs) to treat aggressive hematologic malignancies in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are 2 main types of CPIs, which work through activation of the immune system. On one hand, CPIs can achieve graft-versus-tumor effect, and on the other hand, there is a risk of graft-versus-host disease (GVHD). After a comprehensive literature review, we included data (n = 283) from 24 studies (11 original manuscripts and 13 case reports or case series) and evaluated the results to assess the safety and efficacy of CPI use in conjunction with allo-HSCT. Among the 283 patients, 107 received CPI before allo-HSCT, and 176 received CPI after allo-HSCT. The most common indication for CPI use was for Hodgkin lymphoma. The CPIs used in various studies included ipilimumab, nivolumab, and pembrolizumab. Among the patients exposed to CPI before allo-HSCT, 56% developed acute GVHD and 29% developed chronic GVHD. Investigators reported 20 deaths, 60% of which were GVHD-related. The overall mortality risk with GVHD is 11%. In this group, investigators noted an objective response rate (ORR) in 68% of patients, with complete remission (CR) in 47%, partial remission (PR) in 21%, and stable disease in 11%. Among the patients who received a CPI after allo-HSCT for disease relapse, 14% developed acute GVHD and 9% developed chronic GVHD. Investigators reported 40 deaths, 28% of which were GVHD-related. The mortality risk with GVHD is approximately 7%. Investigators reported ORR in 54% of patients, with CR in 33%, PR in 21%, and disease stabilization in 5%. After careful evaluation of collective data, we found that CPI use both before and after allo-HSCT can be highly effective, but exposure can lead to a significantly increased risk of GVHD-related morbidity and mortality in this patient population. Despite limited availability of data, there is need for extreme caution while making decisions regarding the use o