Pembrolizumab-induced Remission After Failure of Axicabtagene Ciloleucel: Case Report and Literature Review

Overview

Journal In Vivo

Specialty Oncology

Date 2021 Oct 26

PMID 34697175

Citations 3

Authors

Maria Dimou

Aikaterini Bitsani

Wolfgang Bethge

Panayiotis Panayiotidis

Theodoros P Vassilakopoulos

Affiliations

Soon will be listed here.

Abstract

Background: Failure after CD19-directed chimeric antigen receptor (CAR) T-cell therapy for patients with large B-cell B non-Hodgkin lymphoma, especially when it happens early, is an emerging clinical problem. There are no specific recommendations and therefore treatment of these patients remains empiricaI. Immune checkpoint inhibitors are becoming a therapeutic option for these patients.

Case Report: We present a case of a primary mediastinal large B-cell lymphoma who experienced relapse 3.5 months after axicabtagene-ciloleucel therapy and received pembrolizumab. After four cycles of pembrolizumab, complete metabolic response was confirmed. Treatment was discontinued after the sixth cycle due to immune checkpoint inhibitor-related pneumonitis. The disease remains in remission 8 months after the last pembrolizumab dose. We propose mechanisms of action and optimal duration of pembrolizumab treatment in this setting. Finally, we review the existing literature on the sequential administration of CD19-directed CAR T-cell therapy and immune checkpoint inhibitors.

Conclusion: Immune checkpoint inhibitors are a promising treatment option for patients after failure of CD19-directed CAR-T cell therapy.

Citing Articles

Current Issues and Future Perspectives of Targeted Therapies in Primary Mediastinal Large B-Cell Lymphoma.

Liaskas A, Dimopoulou M, Piperidou A, Angelopoulou M, Vassilakopoulos T J Clin Med. 2025; 14(4).

PMID: 40004722 PMC: 11856677. DOI: 10.3390/jcm14041191.

Harnessing the Immune System: An Effective Way to Manage Diffuse Large B-Cell Lymphoma.

Visweshwar N, Rico J, Killeen R, Manoharan A J Hematol. 2023; 12(4):145-160.

PMID: 37692863 PMC: 10482611. DOI: 10.14740/jh1112.

Monoclonal Antibodies in the Treatment of Diffuse Large B-Cell Lymphoma: Moving beyond Rituximab.

Papageorgiou S, Thomopoulos T, Liaskas A, Vassilakopoulos T Cancers (Basel). 2022; 14(8).

PMID: 35454825 PMC: 9026383. DOI: 10.3390/cancers14081917.

Advanced Therapy Medicinal Products' Translation in Europe: A Developers' Perspective.

Pizevska M, Kaeda J, Fritsche E, Elazaly H, Reinke P, Amini L Front Med (Lausanne). 2022; 9:757647.

PMID: 35186986 PMC: 8851388. DOI: 10.3389/fmed.2022.757647.

References

Dunleavy K, Pittaluga S, Maeda L, Advani R, Chen C, Hessler J . Dose-adjusted EPOCH-rituximab therapy in primary mediastinal B-cell lymphoma. N Engl J Med. 2013; 368(15):1408-16. PMC: 4568999. DOI: 10.1056/NEJMoa1214561. View

Armand P, Rodig S, Melnichenko V, Thieblemont C, Bouabdallah K, Tumyan G . Pembrolizumab in Relapsed or Refractory Primary Mediastinal Large B-Cell Lymphoma. J Clin Oncol. 2019; 37(34):3291-3299. PMC: 6881098. DOI: 10.1200/JCO.19.01389. View

Cao Y, Lu W, Sun R, Jin X, Cheng L, He X . Anti-CD19 Chimeric Antigen Receptor T Cells in Combination With Nivolumab Are Safe and Effective Against Relapsed/Refractory B-Cell Non-hodgkin Lymphoma. Front Oncol. 2019; 9:767. PMC: 6709654. DOI: 10.3389/fonc.2019.00767. View

Kuruvilla J, Pintilie M, Tsang R, Nagy T, Keating A, Crump M . Salvage chemotherapy and autologous stem cell transplantation are inferior for relapsed or refractory primary mediastinal large B-cell lymphoma compared with diffuse large B-cell lymphoma. Leuk Lymphoma. 2008; 49(7):1329-36. DOI: 10.1080/10428190802108870. View

Sehn L, Antin J, Shulman L, Mauch P, Elias A, Kadin M . Primary diffuse large B-cell lymphoma of the mediastinum: outcome following high-dose chemotherapy and autologous hematopoietic cell transplantation. Blood. 1998; 91(2):717-23. View

Vassilakopoulos T, Michail M, Papageorgiou S, Kourti G, Angelopoulou M, Panitsas F . Identification of Very Low-Risk Subgroups of Patients with Primary Mediastinal Large B-Cell Lymphoma Treated with R-CHOP. Oncologist. 2021; 26(7):597-609. PMC: 8265336. DOI: 10.1002/onco.13789. View

Nie Y, Lu W, Chen D, Tu H, Guo Z, Zhou X . Mechanisms underlying CD19-positive ALL relapse after anti-CD19 CAR T cell therapy and associated strategies. Biomark Res. 2020; 8:18. PMC: 7254656. DOI: 10.1186/s40364-020-00197-1. View

Liu P, Wang K, Xia Y, Bi X, Sun P, Wang Y . Racial patterns of patients with primary mediastinal large B-cell lymphoma: SEER analysis. Medicine (Baltimore). 2016; 95(27):e4054. PMC: 5058818. DOI: 10.1097/MD.0000000000004054. View

Cheson B, Fisher R, Barrington S, Cavalli F, Schwartz L, Zucca E . Recommendations for initial evaluation, staging, and response assessment of Hodgkin and non-Hodgkin lymphoma: the Lugano classification. J Clin Oncol. 2014; 32(27):3059-68. PMC: 4979083. DOI: 10.1200/JCO.2013.54.8800. View

10.

Cheson B, Pfistner B, Juweid M, Gascoyne R, Specht L, Horning S . Revised response criteria for malignant lymphoma. J Clin Oncol. 2007; 25(5):579-86. DOI: 10.1200/JCO.2006.09.2403. View

11.

Cherkassky L, Morello A, Villena-Vargas J, Feng Y, Dimitrov D, Jones D . Human CAR T cells with cell-intrinsic PD-1 checkpoint blockade resist tumor-mediated inhibition. J Clin Invest. 2016; 126(8):3130-44. PMC: 4966328. DOI: 10.1172/JCI83092. View

12.

Doan A, Pulsipher M . Hypogammaglobulinemia due to CAR T-cell therapy. Pediatr Blood Cancer. 2017; 65(4). PMC: 7477537. DOI: 10.1002/pbc.26914. View

13.

Schuster S, Bishop M, Tam C, Waller E, Borchmann P, McGuirk J . Tisagenlecleucel in Adult Relapsed or Refractory Diffuse Large B-Cell Lymphoma. N Engl J Med. 2018; 380(1):45-56. DOI: 10.1056/NEJMoa1804980. View

14.

Kalisz K, Ramaiya N, Laukamp K, Gupta A . Immune Checkpoint Inhibitor Therapy-related Pneumonitis: Patterns and Management. Radiographics. 2019; 39(7):1923-1937. DOI: 10.1148/rg.2019190036. View

15.

Kansagra A, Frey N, Bar M, Laetsch T, Carpenter P, Savani B . Clinical Utilization of Chimeric Antigen Receptor T Cells in B Cell Acute Lymphoblastic Leukemia: An Expert Opinion from the European Society for Blood and Marrow Transplantation and the American Society for Blood and Marrow Transplantation. Biol Blood Marrow Transplant. 2018; 25(3):e76-e85. PMC: 8335749. DOI: 10.1016/j.bbmt.2018.12.068. View

16.

Vassilakopoulos T, Pangalis G, Katsigiannis A, Papageorgiou S, Constantinou N, Terpos E . Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone with or without radiotherapy in primary mediastinal large B-cell lymphoma: the emerging standard of care. Oncologist. 2012; 17(2):239-49. PMC: 3286173. DOI: 10.1634/theoncologist.2011-0275. View

17.

Park J, Riviere I, Gonen M, Wang X, Senechal B, Curran K . Long-Term Follow-up of CD19 CAR Therapy in Acute Lymphoblastic Leukemia. N Engl J Med. 2018; 378(5):449-459. PMC: 6637939. DOI: 10.1056/NEJMoa1709919. View

18.

Bukhari A, El Chaer F, Koka R, Singh Z, Hutnick E, Ruehle K . Rapid relapse of large B-cell lymphoma after CD19 directed CAR-T-cell therapy due to CD-19 antigen loss. Am J Hematol. 2019; 94(10):E273-E275. DOI: 10.1002/ajh.25591. View

19.

Neelapu S, Locke F, Bartlett N, Lekakis L, Miklos D, Jacobson C . Axicabtagene Ciloleucel CAR T-Cell Therapy in Refractory Large B-Cell Lymphoma. N Engl J Med. 2017; 377(26):2531-2544. PMC: 5882485. DOI: 10.1056/NEJMoa1707447. View