aGvHD,   GvHD Prophylaxis,  cGvHD

Checkpoint inhibitors administered before and after allo-HSCT may increase the risk of graft-versus-host disease

Awais Ijaz from the University of Arizona, Tucson, AZ, USA, and colleagues retrospectively evaluated the safety, efficacy and risks of checkpoint inhibitors (CPIs) in patients with hematological malignancies undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT). CPIs can enhance graft versus tumor (GVT) effect, whereas the risk of graft-versus-host disease (GvHD) may increase. The study was published in Biology of Blood and Marrow Transplantation.

Twenty-four articles (13 case reports and 11 original manuscripts) were selected from PubMed regarding CPIs administered for patients with hematological malignancies either before or after allo-HSCT.

Study overview
  • N = 283 patients
  • Original articles
    • CPI was administered before allo-HSCT in 107 patients
      • N = 91 patients received nivolumab
      • N = 11 patients received pembrolizumab
      • N = 8 patients received ipilimumab
    • CPI was administered after allo-HSCT in 150 patients
      • N = 62 patients received nivolumab
      • N = 85 patients received ipilimumab
      • N = 4 patients received pembrolizumab
    • Case reports
      • CPI was administered after allo-HSCT in 26 patients
        • N = 14 patients received nivolumab
        • N = 12 patients received pembrolizumab
Key findings
Data from original articles
  • Safety and efficacy when CPI was given prior to allo-HSCT
    • GvHD
      • Hyper-acute GvHD: 8 patients (7%)
      • Acute GvHD: 60 patients (56%)
      • Chronic GvHD: 20 patients (29%)
    • Overall response rate (ORR) in 62 evaluable patients: 68% (42/62)
      • Complete response (CR): 47% (29/62)
      • Partial response (PR): 21% (13/62)
    • Stable disease (SD): 11% (7/62)
    • Progressive disease (PD): 19% (12/62)
    • Twenty patients died, 12 deaths occurred due to GvHD
  • Safety and efficacy when CPI was given after allo-HSCT
    • GvHD
      • Acute GvHD: 19 patients (13%)
      • Chronic GvHD: 7 patients (11%)
    • ORR: 59 patients (48%)
      • CR: 34 patients (28%)
      • PR: 25 patients (20%)
    • SD: 7 patients (6 %)
    • PD: 4 patients (3%)
    • Thirty-five patients died, 10 deaths were GvHD related
Data from case reports
  • Safety and efficacy when CPI was given after allo-HSCT
    • CR: 15 patients (58%)
    • PR: 7 patients (30%)
    • SD: 1 patient (4%)
    • PD: 1 patient (4%)
    • GvHD
      • Acute GvHD: 5 patients (19%)
      • One patient (4%) had an exacerbation of existing GvHD
    • 15% of patients died, one of them due to GvHD

The authors concluded that the rate of acute GvHD was high (56%) in patients who received CPI therapy prior to allo-HSCT. They added that “this rate is higher than the historical incidence that ranges between 26% to 50%.” In addition, CPIs received after allo-HSCT led to superior efficacy, but also increased the risk of GvHD (14% acute, 9% chronic). The study group further stated that “there is need for extreme caution while making decisions regarding the use of CPI.” Further prospective clinical trials are required to confirm these findings.

References
  1. Ijaz A. et al. Significant Risk of Graft-versus-Host Disease with Exposure to Checkpoint Inhibitors Before and After Allogeneic transplantation. Biol Blood Marrow Transplant. 2018 Sep 5. DOI: 1016/j.bbmt.2018.08.028. [Epub ahead of print].
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