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Published in: Journal of Medical Case Reports 1/2021

Open Access 01-12-2021 | Lymphoma | Case report

Atezolizumab in combination with intrathecal chemotherapy and radiation for treatment of isolated cerebral nervous system relapse in a patient with extranodal NK/T cell lymphoma: a case report

Authors: Amanda E. Lipsitt, Jaclyn Y. Hung, Anne-Marie Langevin

Published in: Journal of Medical Case Reports | Issue 1/2021

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Abstract

Background

Extranodal NK/T cell lymphoma (ENKTL) is an aggressive form of Epstein-Barr virus (EBV)-associated non-Hodgkin’s lymphoma which historically has a poor prognosis. When relapse occurs, particularly in the cerebral nervous system (CNS), survival is rare. The immune checkpoint pathway family of proteins is highly expressed in many human tumors, especially in EBV-related malignancies. To the best of our knowledge, there are no reports of immune checkpoint inhibitors used either alone or in combination for the treatment of ENTKL CNS relapse, yet there are promising results in metastatic CNS involvement of other malignancies.

Case presentation

This is the case of a 29-year-old Hispanic male with ENKTL who was treated at first relapse with 24 doses of the programmed death-ligand 1 (PD-L1) immune checkpoint inhibitor, atezolizumab, over a 17-month period. He remained in remission for 18 months until he experienced an isolated CNS relapse and on-going evidence of chronic EBV infection. Salvage therapy was provided as a combination of triple intrathecal (TIT) chemotherapy, radiation, and atezolizumab. He continues on maintenance atezolizumab and remains alive 1-year post CNS relapse.

Conclusions

The results from this case suggest that atezolizumab should be considered as part of the treatment regimen for relapsed ENKTL. They also demonstrate the benefit of using atezolizumab in combination with TIT chemotherapy and radiation as a viable treatment option for ENKTL CNS relapse and indicate that atezolizumab is an option for long-term maintenance therapy for patients with ENKTL.
Literature
1.
go back to reference Al-Hamadani M, Habermann TM, Cerhan JR, Macon WR, Maurer MJ, Go RS. Non-Hodgkin lymphoma subtype distribution, geodemographic patterns, and survival in the US: a longitudinal analysis of the National Cancer Data Base from 1998 to 2011. Am J Hematol. 2015;90(9):790–5.CrossRef Al-Hamadani M, Habermann TM, Cerhan JR, Macon WR, Maurer MJ, Go RS. Non-Hodgkin lymphoma subtype distribution, geodemographic patterns, and survival in the US: a longitudinal analysis of the National Cancer Data Base from 1998 to 2011. Am J Hematol. 2015;90(9):790–5.CrossRef
2.
go back to reference Tse E, Kwong YL. The diagnosis and management of NK/T-cell lymphomas. J Hematol Oncol. 2017;10(1):85.CrossRef Tse E, Kwong YL. The diagnosis and management of NK/T-cell lymphomas. J Hematol Oncol. 2017;10(1):85.CrossRef
3.
go back to reference Nevel KS, Pentsova E, Daras M. Clinical presentation, treatment, and outcomes of patients with central nervous system involvement in extranodal natural killer/T-cell lymphoma. Leuk Lymphoma. 2019;60(7):1677–84.CrossRef Nevel KS, Pentsova E, Daras M. Clinical presentation, treatment, and outcomes of patients with central nervous system involvement in extranodal natural killer/T-cell lymphoma. Leuk Lymphoma. 2019;60(7):1677–84.CrossRef
4.
go back to reference Kim TM, Park YH, Lee SY, Kim JH, Kim DW, Im SA, et al. Local tumor invasiveness is more predictive of survival than International Prognostic Index in stage I(E)/II(E) extranodal NK/T-cell lymphoma, nasal type. Blood. 2005;106(12):3785–90.CrossRef Kim TM, Park YH, Lee SY, Kim JH, Kim DW, Im SA, et al. Local tumor invasiveness is more predictive of survival than International Prognostic Index in stage I(E)/II(E) extranodal NK/T-cell lymphoma, nasal type. Blood. 2005;106(12):3785–90.CrossRef
5.
go back to reference Gurion R, Mehta N, Migliacci JC, Zelenetz A, Moskowitz A, Lunning M, et al. Central nervous system involvement in T-cell lymphoma: a single center experience. Acta Oncol. 2016;55(5):561–6.CrossRef Gurion R, Mehta N, Migliacci JC, Zelenetz A, Moskowitz A, Lunning M, et al. Central nervous system involvement in T-cell lymphoma: a single center experience. Acta Oncol. 2016;55(5):561–6.CrossRef
6.
go back to reference Ellin F, Landström J, Jerkeman M, Relander T. Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study. Blood. 2015;126(1):36–41.CrossRef Ellin F, Landström J, Jerkeman M, Relander T. Central nervous system relapse in peripheral T-cell lymphomas: a Swedish Lymphoma Registry study. Blood. 2015;126(1):36–41.CrossRef
7.
go back to reference Chihara D, Fanale MA, Miranda RN, Noorani M, Westin JR, Nastoupil LJ, et al. The risk of central nervous system relapses in patients with peripheral T-cell lymphoma. PLoS One. 2018;13(3):e0191461.CrossRef Chihara D, Fanale MA, Miranda RN, Noorani M, Westin JR, Nastoupil LJ, et al. The risk of central nervous system relapses in patients with peripheral T-cell lymphoma. PLoS One. 2018;13(3):e0191461.CrossRef
8.
go back to reference Bokstein F, Lossos A, Lossos IS, Siegal T. Central nervous system relapse of systemic non-Hodgkin’s lymphoma: results of treatment based on high-dose methotrexate combination chemotherapy. Leuk Lymphoma. 2002;43(3):587–93.CrossRef Bokstein F, Lossos A, Lossos IS, Siegal T. Central nervous system relapse of systemic non-Hodgkin’s lymphoma: results of treatment based on high-dose methotrexate combination chemotherapy. Leuk Lymphoma. 2002;43(3):587–93.CrossRef
9.
go back to reference El-Galaly TC, Cheah CY, Bendtsen MD, Nowakowski GS, Kansara R, Savage KJ, et al. Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma. Eur J Cancer. 2018;93:57–68.CrossRef El-Galaly TC, Cheah CY, Bendtsen MD, Nowakowski GS, Kansara R, Savage KJ, et al. Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma. Eur J Cancer. 2018;93:57–68.CrossRef
10.
go back to reference Chen BJ, Chapuy B, Ouyang J, Sun HH, Roemer MG, Xu ML, et al. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013;19(13):3462–73.CrossRef Chen BJ, Chapuy B, Ouyang J, Sun HH, Roemer MG, Xu ML, et al. PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies. Clin Cancer Res. 2013;19(13):3462–73.CrossRef
11.
go back to reference Bi XW, Wang H, Zhang WW, Wang JH, Liu WJ, Xia ZJ, et al. PD-L1 is upregulated by EBV-driven LMP1 through NF-κB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma. J Hematol Oncol. 2016;9(1):109.CrossRef Bi XW, Wang H, Zhang WW, Wang JH, Liu WJ, Xia ZJ, et al. PD-L1 is upregulated by EBV-driven LMP1 through NF-κB pathway and correlates with poor prognosis in natural killer/T-cell lymphoma. J Hematol Oncol. 2016;9(1):109.CrossRef
12.
go back to reference Jo JC, Kim M, Choi Y, Kim HJ, Kim JE, Chae SW, et al. Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma, nasal type. Ann Hematol. 2017;96(1):25–31.CrossRef Jo JC, Kim M, Choi Y, Kim HJ, Kim JE, Chae SW, et al. Expression of programmed cell death 1 and programmed cell death ligand 1 in extranodal NK/T-cell lymphoma, nasal type. Ann Hematol. 2017;96(1):25–31.CrossRef
14.
go back to reference Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017;129(17):2437–42.CrossRef Kwong YL, Chan TSY, Tan D, Kim SJ, Poon LM, Mow B, et al. PD1 blockade with pembrolizumab is highly effective in relapsed or refractory NK/T-cell lymphoma failing l-asparaginase. Blood. 2017;129(17):2437–42.CrossRef
16.
go back to reference Jeong SH, Song HN, Park JS, Yang DH, Koh Y, Yoon SS, et al. Allogeneic stem cell transplantation for patients with natural killer/T cell lymphoid malignancy: a multicenter analysis comparing upfront and salvage transplantation. Biol Blood Marrow Transpl. 2018;24(12):2471–8.CrossRef Jeong SH, Song HN, Park JS, Yang DH, Koh Y, Yoon SS, et al. Allogeneic stem cell transplantation for patients with natural killer/T cell lymphoid malignancy: a multicenter analysis comparing upfront and salvage transplantation. Biol Blood Marrow Transpl. 2018;24(12):2471–8.CrossRef
17.
go back to reference Yamaguchi M, Suzuki R, Oguchi M. Advances in the treatment of extranodal NK/T-cell lymphoma, nasal type. Blood. 2018;131(23):2528–40.CrossRef Yamaguchi M, Suzuki R, Oguchi M. Advances in the treatment of extranodal NK/T-cell lymphoma, nasal type. Blood. 2018;131(23):2528–40.CrossRef
18.
go back to reference Li X, Cheng Y, Zhang M, Yan J, Li L, Fu X, et al. Activity of pembrolizumab in relapsed/refractory NK/T-cell lymphoma. J Hematol Oncol. 2018;11(1):15.CrossRef Li X, Cheng Y, Zhang M, Yan J, Li L, Fu X, et al. Activity of pembrolizumab in relapsed/refractory NK/T-cell lymphoma. J Hematol Oncol. 2018;11(1):15.CrossRef
19.
go back to reference Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol. 2016;17(7):976–83.CrossRef Goldberg SB, Gettinger SN, Mahajan A, Chiang AC, Herbst RS, Sznol M, et al. Pembrolizumab for patients with melanoma or non-small-cell lung cancer and untreated brain metastases: early analysis of a non-randomised, open-label, phase 2 trial. Lancet Oncol. 2016;17(7):976–83.CrossRef
20.
go back to reference Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018;19(5):672–81.CrossRef Long GV, Atkinson V, Lo S, Sandhu S, Guminski AD, Brown MP, et al. Combination nivolumab and ipilimumab or nivolumab alone in melanoma brain metastases: a multicentre randomised phase 2 study. Lancet Oncol. 2018;19(5):672–81.CrossRef
21.
go back to reference De Giorgi U, Cartenì G, Giannarelli D, Basso U, Galli L, Cortesi E, et al. Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real-world results from an expanded access programme. BJU Int. 2019;123(1):98–105.CrossRef De Giorgi U, Cartenì G, Giannarelli D, Basso U, Galli L, Cortesi E, et al. Safety and efficacy of nivolumab for metastatic renal cell carcinoma: real-world results from an expanded access programme. BJU Int. 2019;123(1):98–105.CrossRef
22.
go back to reference Nayak L, Iwamoto FM, LaCasce A, Mukundan S, Roemer MGM, Chapuy B, et al. PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma. Blood. 2017;129(23):3071–3.CrossRef Nayak L, Iwamoto FM, LaCasce A, Mukundan S, Roemer MGM, Chapuy B, et al. PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma. Blood. 2017;129(23):3071–3.CrossRef
23.
go back to reference Nakayama A, Abe H, Kunita A, Saito R, Kanda T, Yamashita H, et al. Viral loads correlate with upregulation of PD-L1 and worse patient prognosis in Epstein-Barr Virus-associated gastric carcinoma. PLoS One. 2019;14(1):e0211358.CrossRef Nakayama A, Abe H, Kunita A, Saito R, Kanda T, Yamashita H, et al. Viral loads correlate with upregulation of PD-L1 and worse patient prognosis in Epstein-Barr Virus-associated gastric carcinoma. PLoS One. 2019;14(1):e0211358.CrossRef
24.
go back to reference Kim SJ, Oh SY, Hong JY, Chang MH, Lee DH, Huh J, et al. When do we need central nervous system prophylaxis in patients with extranodal NK/T-cell lymphoma, nasal type? Ann Oncol. 2010;21(5):1058–63.CrossRef Kim SJ, Oh SY, Hong JY, Chang MH, Lee DH, Huh J, et al. When do we need central nervous system prophylaxis in patients with extranodal NK/T-cell lymphoma, nasal type? Ann Oncol. 2010;21(5):1058–63.CrossRef
Metadata
Title
Atezolizumab in combination with intrathecal chemotherapy and radiation for treatment of isolated cerebral nervous system relapse in a patient with extranodal NK/T cell lymphoma: a case report
Authors
Amanda E. Lipsitt
Jaclyn Y. Hung
Anne-Marie Langevin
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Journal of Medical Case Reports / Issue 1/2021
Electronic ISSN: 1752-1947
DOI
https://doi.org/10.1186/s13256-021-02740-6

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