Skip to main content
Erschienen in: International Journal of Hematology 1/2017

17.01.2017 | Case Report

Successful treatment with low-dose nivolumab in refractory Hodgkin lymphoma after allogeneic stem cell transplantation

verfasst von: Makoto Onizuka, Minoru Kojima, Keiko Matsui, Shinichiro Machida, Masako Toyosaki, Yasuyuki Aoyama, Hidetsugu Kawai, Jun Amaki, Ryujiro Hara, Akifumi Ichiki, Yoshiaki Ogawa, Hiroshi Kawada, Naoya Nakamura, Kiyoshi Ando

Erschienen in: International Journal of Hematology | Ausgabe 1/2017

Einloggen, um Zugang zu erhalten

Abstract

Previous studies have reported that an antibody that blocks programmed cell death 1 (PD-1) has therapeutic activity in patients with refractory/relapsed Hodgkin lymphoma (HL). However, the safety and efficacy of these agents in the post-allogeneic stem cell transplantation (allo-SCT) setting are not well known. Here, we describe a patient who was diagnosed as classical HL and treated with five regimens of chemotherapies with autologous SCT. Complete remission (CR) was not achieved following this initial treatment, so we performed allo-SCT from an HLA-matched sibling donor. Since his disease progressed at day 403 after allo-SCT, we decided to use nivolumab in the treatment of his refractory disease. To prevent the worsening of his chronic graft-versus-host disease (GVHD), we reduced the initial dose and frequency of nivolumab compared with the previous report. After four courses of 0.5 mg/kg of nivolumab every three weeks, FDG-PET imaging showed partial response (PR) to the treatment, a remarkable result. However, since the escalated dose of 2 mg/kg resulted in worsening of dyspnea and skin sclerosis, we initiated systemic administration of prednisolone and reduced nivolumab to 1 mg/kg. At the time of this report, his HL is in stable PR with three weekly administration of nivolumab and steroid controlled mild chronic GVHD.
Literatur
1.
Zurück zum Zitat Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. New Engl J Med. 2015;372:311–9.CrossRefPubMed Ansell SM, Lesokhin AM, Borrello I, Halwani A, Scott EC, Gutierrez M, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma. New Engl J Med. 2015;372:311–9.CrossRefPubMed
2.
Zurück zum Zitat Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, et al. Tumor antigen–specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009;114:1537–44.CrossRefPubMedPubMedCentral Ahmadzadeh M, Johnson LA, Heemskerk B, Wunderlich JR, Dudley ME, White DE, et al. Tumor antigen–specific CD8 T cells infiltrating the tumor express high levels of PD-1 and are functionally impaired. Blood. 2009;114:1537–44.CrossRefPubMedPubMedCentral
3.
Zurück zum Zitat Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T. Minato N Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA. 2002;99:12293–7.CrossRefPubMedPubMedCentral Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T. Minato N Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci USA. 2002;99:12293–7.CrossRefPubMedPubMedCentral
4.
Zurück zum Zitat Cheah CY, Fowler NH. Wang ML breakthrough therapies in B-cell non-Hodgkin lymphoma. Ann Oncol. 2016;27:778–87.CrossRefPubMed Cheah CY, Fowler NH. Wang ML breakthrough therapies in B-cell non-Hodgkin lymphoma. Ann Oncol. 2016;27:778–87.CrossRefPubMed
5.
Zurück zum Zitat Singh AK, Porrata LF, Aljitawi O, Lin T, Shune L, Ganguly S, et al. Fatal GvHD induced by PD-1 inhibitor pembrolizumab in a patient with Hodgkin/’s lymphoma. Bone Marrow Transplant. 2016;51:1268–70.CrossRefPubMed Singh AK, Porrata LF, Aljitawi O, Lin T, Shune L, Ganguly S, et al. Fatal GvHD induced by PD-1 inhibitor pembrolizumab in a patient with Hodgkin/’s lymphoma. Bone Marrow Transplant. 2016;51:1268–70.CrossRefPubMed
6.
Zurück zum Zitat Yared JA, Hardy N, Singh Z, Hajj S, Badros AZ, Kocoglu M, et al. Major clinical response to nivolumab in relapsed/refractory Hodgkin lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant. 2016;51:850–2.CrossRefPubMed Yared JA, Hardy N, Singh Z, Hajj S, Badros AZ, Kocoglu M, et al. Major clinical response to nivolumab in relapsed/refractory Hodgkin lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant. 2016;51:850–2.CrossRefPubMed
7.
Zurück zum Zitat Hasenclever D, Diehl V, Armitage JO, Assouline D, Björkholm M, Brusamolino E, et al. A prognostic score for advanced Hodgkin’s disease. New Engl J Med. 1998;339:1506–14.CrossRefPubMed Hasenclever D, Diehl V, Armitage JO, Assouline D, Björkholm M, Brusamolino E, et al. A prognostic score for advanced Hodgkin’s disease. New Engl J Med. 1998;339:1506–14.CrossRefPubMed
8.
Zurück zum Zitat Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, et al. Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016;17:1283–94.CrossRefPubMed Younes A, Santoro A, Shipp M, Zinzani PL, Timmerman JM, Ansell S, et al. Nivolumab for classical Hodgkin’s lymphoma after failure of both autologous stem-cell transplantation and brentuximab vedotin: a multicentre, multicohort, single-arm phase 2 trial. Lancet Oncol. 2016;17:1283–94.CrossRefPubMed
9.
Zurück zum Zitat Blazar BR, Carreno BM, Panoskaltsis-Mortari A, Carter L, Iwai Y, Yagita H, et al. Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-γ-dependent mechanism. J Immunol. 2003;171:1272–7.CrossRefPubMed Blazar BR, Carreno BM, Panoskaltsis-Mortari A, Carter L, Iwai Y, Yagita H, et al. Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-γ-dependent mechanism. J Immunol. 2003;171:1272–7.CrossRefPubMed
10.
Zurück zum Zitat Blazar BR, Taylor PA, Panoskaltsis-Mortari A, Sharpe AH, Vallera DA. Opposing roles of CD28:B7 and CTLA-4:B7 pathways in regulating in vivo alloresponses in murine recipients of MHC disparate T cells. J Immunol. 1999;162:6368–77.PubMed Blazar BR, Taylor PA, Panoskaltsis-Mortari A, Sharpe AH, Vallera DA. Opposing roles of CD28:B7 and CTLA-4:B7 pathways in regulating in vivo alloresponses in murine recipients of MHC disparate T cells. J Immunol. 1999;162:6368–77.PubMed
11.
Zurück zum Zitat Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, et al. Ipilimumab for patients with relapse after allogeneic transplantation. New Engl J Med. 2016;375:143–53.CrossRefPubMedPubMedCentral Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, et al. Ipilimumab for patients with relapse after allogeneic transplantation. New Engl J Med. 2016;375:143–53.CrossRefPubMedPubMedCentral
12.
Zurück zum Zitat Nishino M, Sholl LM, Hatabu H, Ramaiya NH. Hodi FS Anti–PD-1–Related pneumonitis during cancer immunotherapy. New Engl J Med. 2015;373:288–90.CrossRefPubMedPubMedCentral Nishino M, Sholl LM, Hatabu H, Ramaiya NH. Hodi FS Anti–PD-1–Related pneumonitis during cancer immunotherapy. New Engl J Med. 2015;373:288–90.CrossRefPubMedPubMedCentral
13.
Zurück zum Zitat Watanabe S, Kimura H, Takato H, Waseda Y, Hara J, Sone T, et al. Severe pneumonitis after nivolumab treatment in a patient with melanoma. Allergol Int. 2016;65:487–9.CrossRefPubMed Watanabe S, Kimura H, Takato H, Waseda Y, Hara J, Sone T, et al. Severe pneumonitis after nivolumab treatment in a patient with melanoma. Allergol Int. 2016;65:487–9.CrossRefPubMed
14.
Zurück zum Zitat Alinari L. Blum KA How I treat relapsed classical Hodgkin lymphoma after autologous stem cell transplant. Blood. 2016;127:287–95.CrossRefPubMed Alinari L. Blum KA How I treat relapsed classical Hodgkin lymphoma after autologous stem cell transplant. Blood. 2016;127:287–95.CrossRefPubMed
Metadaten
Titel
Successful treatment with low-dose nivolumab in refractory Hodgkin lymphoma after allogeneic stem cell transplantation
verfasst von
Makoto Onizuka
Minoru Kojima
Keiko Matsui
Shinichiro Machida
Masako Toyosaki
Yasuyuki Aoyama
Hidetsugu Kawai
Jun Amaki
Ryujiro Hara
Akifumi Ichiki
Yoshiaki Ogawa
Hiroshi Kawada
Naoya Nakamura
Kiyoshi Ando
Publikationsdatum
17.01.2017
Verlag
Springer Japan
Erschienen in
International Journal of Hematology / Ausgabe 1/2017
Print ISSN: 0925-5710
Elektronische ISSN: 1865-3774
DOI
https://doi.org/10.1007/s12185-017-2181-9

Weitere Artikel der Ausgabe 1/2017

International Journal of Hematology 1/2017 Zur Ausgabe

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.