First Report of Severe Acute Graft-Versus-Host Disease After Allogeneic Stem Cell Transplant in a Patient With Myelodysplastic Syndrome Treated With Atezolizumab: Literature Review

Abstract

Checkpoint inhibitors have become a widely used and available immunotherapy option for treating a variety of malignancies, including hematological malignancies. Patients receiving these therapies may go on to receive a curative allogeneic hematopoietic stem cell transplant (allo-HSCT). This presents a clinical challenge as the safety and efficacy of HSCT is not well reported in this subset of patients and residual programmed death-ligand 1 inhibition could potentially enhance allogeneic T-cell responses, improving the graft-versus-tumor effect, but also increasing the incidence and severity of immune complications such as graft-versus-host disease (GVHD). Here, this report includes a detailed literature review summarizing all available data on HSCT outcomes in the setting of using checkpoint inhibitor therapy pre-transplant. Moreover, we report a case of acute GVHD after allo-HSCT in a patient with high-risk myelodysplastic syndrome who received prior atezolizumab therapy, highlighting the importance of further research into this specific population in order to improve transplant-related outcomes.

Genetic and pharmaceutical targeting of HIF1α allows combo-immunotherapy to boost graft vs. leukemia without exacerbation graft vs. host disease

“…Antibodies that block PD1/PDL1 worsen GVHD in both mice and humans. 17 , 25 , 36 We tested the effects of anti-PD1 or anti-PDL1 antibodies in WT or Hif1a −/− T cell recipients ( Figure 1 A). Consistent with an earlier study, 25 anti-PD1 or anti-PDL1 exacerbated GVHD in WT T cell recipients, leading to decreased survival ( Figure 1 B).…”

Targeting SLP76:ITK interaction separates GVHD from GVL in allo-HSCT

“…The retention of T cells in secondary lymphoid organs by FTY720-mediated inhibition of S1PR1 also ameliorates GVHD while maintaining GVL effects ( Villarroel et al., 2014 ; Liu et al., 2012 ).The chemokine receptor CXCR3 has an important role in the migration of effector T cells in GVHD model ( Duffner et al., 2003 ). CX3r1, CXCr1, CCR12, CrTAM, CXCR6, CCR9, CXCR5, and CXCR4 have been shown to play a significant role in donor T cell migration to GVHD target organs ( Barrett, 2015 ; Castor et al., 2012 ; Hsiao et al., 2020 ). In a clinical study, blockade of these chemokine receptors by a small molecule antagonist led to a reduction in GVHD with no significant difference in relapse rates, suggesting that blocking T cell migration to target tissues could reduce GVHD severity without compromising the beneficial GVL effect ( Vadakekolathu and Rutella, 2017 ).…”

Retention of Donor T Cells in Lymphohematopoietic Tissue and Augmentation of Tissue PD-L1 Protection for Prevention of GVHD While Preserving GVL Activity

“…Administration of anti-PD-1 or anti-PD-L1 mAb to the patients who with tumor relapsed after allo-HCT induced lethal aGVHD ( 179 – 182 ). Since blockade of PD-L1/CD80 interaction reduced but did not completely remove the inhibitory effect of PD-L1/PD-1 interactions, we expect that administration of antibodies to specifically block PD-L1/CD80 interaction will augment GVL effect in lymphoid tissues while maintaining the protective effect of PD-L1/PD-1 interactions in GVHD target tissues.…”