{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T04:13:41Z","timestamp":1792815221702,"version":"4.5.0"},"reference-count":26,"publisher":"American Society of Hematology","issue":"6","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,3,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>A failed graft-versus-tumor (GVT) effect is a common mechanism of relapse after allogeneic hematopoietic cell transplantation (alloHCT). Although targeting the PD-1\/PD-L1 axis may restore GVT effects, PD-1 blockade exacerbates graft-versus-host disease (GVHD) in murine models, and severe GVHD can occur in patients treated with anti-PD-1 therapy after alloHCT. Therefore, we developed a prospective study to assess the safety and efficacy of pembrolizumab in patients relapsing after alloHCT. Eligible patients received pembrolizumab (200 mg every 3 weeks) for up to 2 years. Twelve patients were enrolled (8\u00a0patients with acute myeloid leukemia, 1 patient with myelodysplastic syndrome, 1 patient with classical Hodgkin lymphoma, and 2 patients with diffuse large B-cell lymphoma [DLBCL]). All participants received reduced-intensity preparative regimens with in\u00a0vivo T-cell depletion. The median time from alloHCT to enrollment was 587 days (range, 101-4211). Three participants (25%) experienced grade 3 to 4 immune-related adverse events (irAE) (pneumonitis, 2 patients; hyperthyroidism, 1 patient), all occurring after 1 to 2 cycles, and resolving after pembrolizumab discontinuation and corticosteroid treatment. irAEs of any grade occurred in 5 patients (42%). No treatment-emergent GVHD was observed. Overall and complete response (CR) rates were 22% (2\/9). Both patients achieving CRs had\u00a0PD-L1 gene\u2013amplified lymphomas and diffuse PD-L1 expression on pretreatment biopsies. An acquired EZH2 mutation was identified at relapse in a patient with DLBCL who achieved an initial CR to pembrolizumab, which was associated with downregulated HLA\u00a0expression on malignant B cells, implicating EZH2 mutations as a potential immune escape mechanism after PD-1\u2013blockade therapy. In conclusion, after alloHCT, treatment with pembrolizumab is feasible and associated with objective responses in relapsed lymphoid malignancies but can induce severe irAEs, requiring vigilant monitoring. This\u00a0trial was registered at www.clinicaltrials.gov as #NCT02981914.<\/jats:p>","DOI":"10.1182\/bloodadvances.2022008403","type":"journal-article","created":{"date-parts":[[2022,8,16]],"date-time":"2022-08-16T20:12:14Z","timestamp":1660680734000},"page":"963-970","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":22,"title":["Pembrolizumab for the treatment of disease relapse after allogeneic hematopoietic stem cell transplantation"],"prefix":"10.1182","volume":"7","author":[{"given":"James","family":"Godfrey","sequence":"first","affiliation":[{"name":"1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3190-7807","authenticated-orcid":false,"given":"Hongtao","family":"Liu","sequence":"additional","affiliation":[{"name":"2Section of Hematology\/Oncology, Department of Medicine, University of 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IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0803-9607","authenticated-orcid":false,"given":"Andrew","family":"Artz","sequence":"additional","affiliation":[{"name":"1Department of Hematology & Hematopoietic Cell Transplantation, City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2719-0580","authenticated-orcid":false,"given":"Peter A.","family":"Riedell","sequence":"additional","affiliation":[{"name":"2Section of Hematology\/Oncology, Department of Medicine, University of Chicago, Chicago, IL"},{"name":"3David and Etta Jones Center for Cellular Therapy, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy","family":"Stock","sequence":"additional","affiliation":[{"name":"2Section of Hematology\/Oncology, Department of Medicine, University of Chicago, Chicago, IL"},{"name":"3David and Etta Jones Center for Cellular Therapy, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Theodore","family":"Karrison","sequence":"additional","affiliation":[{"name":"6Department of Public Health Sciences, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carrie","family":"Fitzpatrick","sequence":"additional","affiliation":[{"name":"7Department of Cytogenetics, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Girish","family":"Venkataraman","sequence":"additional","affiliation":[{"name":"8Department of Pathology, University of Chicago, Chicago, IL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9739-0866","authenticated-orcid":false,"given":"Alan","family":"Cooper","sequence":"additional","affiliation":[{"name":"2Section of Hematology\/Oncology, Department of Medicine, University of Chicago, Chicago, 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