Background: Antibodies blocking the PD-1/PD-L1 axis have been shown to have substantial antitumor effects also in the treatment of Hodgkin's lymphoma (HL) relapsing after conventional chemotherapy or even autologous hematopoietic stem cell transplantation (autoHSCT). In the case of allogeneic HSCT (alloHSCT), this treatment bears the risk of inducing graft-versus-host disease (GVHD). So far, only a small number of patients who developed acute GVHD after PD-1 antibody administration are described in the literature. Case Reports: We herein report the cases of 2 HL patients after alloHSCT who both responded well to the therapy; however, 1 patient developed chronic GVHD (cGVHD) within 3 days of administration of nivolumab. This patient already had a history of cGVHD and interestingly showed manifestations at the very same sites. The other patient never showed any signs of cGVHD, even with the administration of 13 cycles of anti-PD-1 therapy and large doses of donor lymphocytes. Conclusion: The rapid reappearance of cGVHD after blockade of PD-1 implies an important role of PD-1/PD-L1 in peripheral immune tolerance in cGVHD after alloHSCT and warrants further investigation.

1.
Green MR, Monti S, Rodig SJ, Juszczynski P, Currie T, O'Donnell E, Chapuy B, Takeyama K, Neuberg D, Golub TR, Kutok JL, Shipp MA: Integrative analysis reveals selective 9p24.1 amplification, increased PD-1 ligand expression, and further induction via JAK2 in nodular sclerosing Hodgkin lymphoma and primary mediastinal large B-cell lymphoma. Blood 2010;116:3268-3277.
2.
Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M: PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med 2015;372:311-319.
3.
Angenendt L, Schliemann C, Lutz M, Rebber E, Schulze AB, Weckesser M, Stegger L, Schäfers M, Groth C, Kessler T, Lenz G, Stelljes M, Berdel WE: Nivolumab in a patient with refractory Hodgkin's lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant 2016;51:443-445.
4.
Villasboas JC, Ansell SM, Witzig TE: Targeting the PD-1 pathway in patients with relapsed classic Hodgkin lymphoma following allogeneic stem cell transplant is safe and effective. Oncotarget 2016;7:13260-13264.
5.
Yared JA, Hardy N, Singh Z, Hajj S, Badros AZ, Kocoglu M, Yanovich S, Sausville EA, Ujjani C, Ruehle K, Goecke C, Landau M, Rapoport AP: Major clinical response to nivolumab in relapsed/refractory Hodgkin lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant 2016;51:850-852.
6.
Singh AK, Porrata LF, Aljitawi O, Lin T, Shune L, Ganguly S, McGuirk JP, Abhyankar S: Fatal GvHD induced by PD-1 inhibitor pembrolizumab in a patient with Hodgkin's lymphoma. Bone Marrow Transplant 2016;51:1268-1270.
7.
Younes A, Gopal AK, Smith SE, Ansell SM, Rosenblatt JD, Savage KJ, Ramchandren R, Bartlett NL, Cheson BD, de Vos S, Forero-Torres A, Moskowitz CH, Connors JM, Engert A, Larsen EK, Kennedy DA, Sievers EL, Chen R: Results of a pivotal phase II study of brentuximab vedotin for patients with relapsed or refractory Hodgkin's lymphoma. J Clin Oncol 2012;30:2183-2189.
8.
Ugocsai P, Wolff D, Menhart K, Hellwig D, Holler E, Herr W, Reichle A: Biomodulatory metronomic therapy induces PET-negative remission in chemo- and brentuximab-refractory Hodgkin lymphoma. Br J Haematol 2016;172:290-293.
9.
Di Ianni M, Ballanti S, Iodice G, Reale A, Falzetti F, Minelli O, Serio G, Martelli MF, Dammacco F, Vacca A, Ria R: High-dose thiotepa, etoposide and carboplatin as conditioning regimen for autologous stem cell transplantation in patients with high-risk Hodgkin's lymphoma. Hematology 2012;17:23-27.
10.
Jagasia MH, Greinix HT, Arora M, Williams KM, Wolff D, Cowen EW, Palmer J, Weisdorf D, Treister NS, Cheng GS, Kerr H, Stratton P, Duarte RF, McDonald GB, Inamoto Y, Vigorito A, Arai S, Datiles MB, Jacobsohn D, Heller T, Kitko CL, Mitchell SA, Martin PJ, Shulman H, Wu RS, Cutler CS, Vogelsang GB, Lee SJ, Pavletic SZ, Flowers ME: National Institutes of Health Consensus Development Project on Criteria for Clinical Trials in Chronic Graft-versus-Host Disease: I. The 2014 Diagnosis and Staging Working Group report. Biol Blood Marrow Transplant 2015;21:389-401.
11.
Herbaux C, Gauthier J, Brice P, Drumez E, Ysebaert L, Doyen H, Fornecker L, Bouabdallah K, Manson G, Ghesquières H, Tabrizi R, Hermet E, Lazarovici J, Thiebaut-Bertrand A, Chauchet A, Demarquette H, Boyle E, Houot R, Yakoub-Agha I, Morschhauser F: Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin's lymphoma. Blood 2017;129:2471-2478.
12.
Blazar BR, Carreno BM, Panoskaltsis-Mortari A, Carter L, Iwai Y, Yagita H, Nishimura H, Taylor PA: Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanism. J Immunol 2003;171:1272-1277.
13.
Saha A, O'Connor RS, Thangavelu G, et al.: Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality. J Clin Invest 2016;126:2642-2660.
14.
Schuchmann M, Meyer RG, Distler E, von Stebut E, Kuball J, Schnürer E, Wölfel T, Theobald M, Konur A, Gregor S, Schreiner O, Huber C, Galle PR, Otto G, Herr W: The programmed death (PD)-1/PD-ligand 1 pathway regulates graft-versus-host-reactive CD8 T cells after liver transplantation. Am J Transplant 2008;8:2434-2444.
15.
Deng R, Cassady K, Li X, Yao S, Zhang M, Racine J, Lin J, Chen L, Zeng D: B7H1/CD80 interaction augments PD-1-dependent T cell apoptosis and ameliorates graft-versus-host disease. J Immunol 2015;194:560-574.
16.
Fujiwara H, Maeda Y, Kobayashi K, Nishimori H, Matsuoka K, Fujii N, Kondo E, Tanaka T, Chen L, Azuma M, Yagita H, Tanimoto M: Programmed death-1 pathway in host tissues ameliorates Th17/Th1-mediated experimental chronic graft-versus-host disease. J Immunol 2014;193:2565-2573.
You do not currently have access to this content.