The programmed-death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) pathways are inhibitory immune checkpoints involved in the escape of cancer cells from the immune system. Inhibition of these immune checkpoints can lead to the induction of body’s immune response to these cancer cells. To activate the immune system against the tumor cells, various monoclonal antibodies targeting these pathways have been developed. Many of such antibodies have been approved for therapy in solid tumor malignancies and now some hematological malignancies. Here, we review the available data regarding the response to PD-1 and CTLA-4 pathway blockade in hematological malignancies including Hodgin lymphoma, non-Hodgkin lymhoma, multiple myeloma and myeloid neoplasms as well as before and after hematopoietic cell transplantation. We also discuss the specific concerns and differences related to their use in hematological malignancies (HMs) as compared to solid tumors.
| Published in | Cancer Research Journal (Volume 9, Issue 2) |
| DOI | 10.11648/j.crj.20210902.16 |
| Page(s) | 122-130 |
| Creative Commons |
This is an Open Access article, distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution and reproduction in any medium or format, provided the original work is properly cited. |
| Copyright |
Copyright © The Author(s), 2024. Published by Science Publishing Group |
Immunotherapy, Checkpoint Inhibition, CPI, PD-1, PD-L1, CTLA-4, Hematological Malignancies
| [1] | Topalian SL, Drake CG, Pardoll DM. Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015; 27 (4): 450-61. |
| [2] | Schneider H, Downey J, Smith A, Zinselmeyer BH, Rush C, Brewer JM, et al. Reversal of the TCR stop signal by CTLA-4. Science. 2006; 313 (5795): 1972-5. |
| [3] | Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med. 2000; 192 (7): 1027-34. |
| [4] | Pardoll DM. The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12 (4): 252-64. |
| [5] | Sharma P, Hu-Lieskovan S, Wargo JA, Ribas A. Primary, Adaptive, and Acquired Resistance to Cancer Immunotherapy. Cell. 2017; 168 (4): 707-23. |
| [6] | Wang Y, Wu L, Tian C, Zhang Y. PD-1-PD-L1 immune-checkpoint blockade in malignant lymphomas. Ann Hematol. 2018; 97 (2): 229-37. |
| [7] | Roemer MG, Advani RH, Ligon AH, Natkunam Y, Redd RA, Homer H, et al. PD-L1 and PD-L2 Genetic Alterations Define Classical Hodgkin Lymphoma and Predict Outcome. J Clin Oncol. 2016; 34 (23): 2690-7. |
| [8] | 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. |
| [9] | Green MR, Monti S, Rodig SJ, Juszczynski P, Currie T, O'Donnell E, et al. 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 (17): 3268-77. |
| [10] | Green MR, Rodig S, Juszczynski P, Ouyang J, Sinha P, O'Donnell E, et al. Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin Cancer Res. 2012; 18 (6): 1611-8. |
| [11] | 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. N Engl J Med. 2015; 372 (4): 311-9. |
| [12] | Armand P, Shipp MA, Ribrag V, Michot JM, Zinzani PL, Kuruvilla J, et al. Programmed Death-1 Blockade With Pembrolizumab in Patients With Classical Hodgkin Lymphoma After Brentuximab Vedotin Failure. J Clin Oncol. 2016; 34 (31): 3733-9. |
| [13] | Chen R, Zinzani PL, Fanale MA, Armand P, Johnson NA, Brice P, et al. Phase II Study of the Efficacy and Safety of Pembrolizumab for Relapsed/Refractory Classic Hodgkin Lymphoma. J Clin Oncol. 2017; 35 (19): 2125-32. |
| [14] | Armand P, Engert A, Younes A, Fanale M, Santoro A, Zinzani PL, et al. Nivolumab for Relapsed/Refractory Classic Hodgkin Lymphoma After Failure of Autologous Hematopoietic Cell Transplantation: Extended Follow-Up of the Multicohort Single-Arm Phase II CheckMate 205 Trial. J Clin Oncol. 2018; 36 (14): 1428-39. |
| [15] | Li Y, Wang J, Li C, Ke XY. Contribution of PD-L1 to oncogenesis of lymphoma and its RNAi-based targeting therapy. Leuk Lymphoma. 2012; 53 (10): 2015-23. |
| [16] | Andorsky DJ, Yamada RE, Said J, Pinkus GS, Betting DJ, Timmerman JM. Programmed death ligand 1 is expressed by non-hodgkin lymphomas and inhibits the activity of tumor-associated T cells. Clin Cancer Res. 2011; 17 (13): 4232-44. |
| [17] | Ansell SM, Stenson M, Habermann TM, Jelinek DF, Witzig TE. Cd4+ T-cell immune response to large B-cell non-Hodgkin's lymphoma predicts patient outcome. J Clin Oncol. 2001; 19 (3): 720-6. |
| [18] | Kiyasu J, Miyoshi H, Hirata A, Arakawa F, Ichikawa A, Niino D, et al. Expression of programmed cell death ligand 1 is associated with poor overall survival in patients with diffuse large B-cell lymphoma. Blood. 2015; 126 (19): 2193-201. |
| [19] | Berger R, Rotem-Yehudar R, Slama G, Landes S, Kneller A, Leiba M, et al. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin Cancer Res. 2008; 14 (10): 3044-51. |
| [20] | Westin JR, Chu F, Zhang M, Fayad LE, Kwak LW, Fowler N, et al. Safety and activity of PD1 blockade by pidilizumab in combination with rituximab in patients with relapsed follicular lymphoma: a single group, open-label, phase 2 trial. Lancet Oncol. 2014; 15 (1): 69-77. |
| [21] | Armand P, Nagler A, Weller EA, Devine SM, Avigan DE, Chen YB, et al. Disabling immune tolerance by programmed death-1 blockade with pidilizumab after autologous hematopoietic stem-cell transplantation for diffuse large B-cell lymphoma: results of an international phase II trial. J Clin Oncol. 2013; 31 (33): 4199-206. |
| [22] | Dorfman DM, Schultze JL, Shahsafaei A, Michalak S, Gribben JG, Freeman GJ, et al. In vivo expression of B7-1 and B7-2 by follicular lymphoma cells can prevent induction of T-cell anergy but is insufficient to induce significant T-cell proliferation. Blood. 1997; 90 (11): 4297-306. |
| [23] | Chaperot L, Plumas J, Jacob MC, Bost F, Molens JP, Sotto JJ, et al. Functional expression of CD80 and CD86 allows immunogenicity of malignant B cells from non-Hodgkin's lymphomas. Exp Hematol. 1999; 27 (3): 479-88. |
| [24] | Ansell SM, Hurvitz SA, Koenig PA, LaPlant BR, Kabat BF, Fernando D, et al. Phase I study of ipilimumab, an anti-CTLA-4 monoclonal antibody, in patients with relapsed and refractory B-cell non-Hodgkin lymphoma. Clin Cancer Res. 2009; 15 (20): 6446-53. |
| [25] | Shi M, Roemer MG, Chapuy B, Liao X, Sun H, Pinkus GS, et al. Expression of programmed cell death 1 ligand 2 (PD-L2) is a distinguishing feature of primary mediastinal (thymic) large B-cell lymphoma and associated with PDCD1LG2 copy gain. Am J Surg Pathol. 2014; 38 (12): 1715-23. |
| [26] | Zinzani PL, Ribrag V, Moskowitz CH, Michot JM, Kuruvilla J, Balakumaran A, et al. Safety and tolerability of pembrolizumab in patients with relapsed/refractory primary mediastinal large B-cell lymphoma. Blood. 2017; 130 (3): 267-70. |
| [27] | Lesokhin AM, Ansell SM, Armand P, Scott EC, Halwani A, Gutierrez M, et al. Nivolumab in Patients With Relapsed or Refractory Hematologic Malignancy: Preliminary Results of a Phase Ib Study. J Clin Oncol. 2016; 34 (23): 2698-704. |
| [28] | Ding W, LaPlant BR, Call TG, Parikh SA, Leis JF, He R, et al. Pembrolizumab in patients with CLL and Richter transformation or with relapsed CLL. Blood. 2017; 129 (26): 3419-27. |
| [29] | Bruno B, Rotta M, Patriarca F, Mordini N, Allione B, Carnevale-Schianca F, et al. A comparison of allografting with autografting for newly diagnosed myeloma. N Engl J Med. 2007; 356 (11): 1110-20. |
| [30] | Bjorkstrand B, Iacobelli S, Hegenbart U, Gruber A, Greinix H, Volin L, et al. Tandem autologous/reduced-intensity conditioning allogeneic stem-cell transplantation versus autologous transplantation in myeloma: long-term follow-up. J Clin Oncol. 2011; 29 (22): 3016-22. |
| [31] | Chung DJ, Pronschinske KB, Shyer JA, Sharma S, Leung S, Curran SA, et al. T-cell Exhaustion in Multiple Myeloma Relapse after Autotransplant: Optimal Timing of Immunotherapy. Cancer Immunol Res. 2016; 4 (1): 61-71. |
| [32] | Atanackovic D, Arfsten J, Cao Y, Gnjatic S, Schnieders F, Bartels K, et al. Cancer-testis antigens are commonly expressed in multiple myeloma and induce systemic immunity following allogeneic stem cell transplantation. Blood. 2007; 109 (3): 1103-12. |
| [33] | Tyler EM, Jungbluth AA, O'Reilly RJ, Koehne G. WT1-specific T-cell responses in high-risk multiple myeloma patients undergoing allogeneic T cell-depleted hematopoietic stem cell transplantation and donor lymphocyte infusions. Blood. 2013; 121 (2): 308-17. |
| [34] | Ray A, Das DS, Song Y, Richardson P, Munshi NC, Chauhan D, et al. Targeting PD1-PDL1 immune checkpoint in plasmacytoid dendritic cell interactions with T cells, natural killer cells and multiple myeloma cells. Leukemia. 2015; 29 (6): 1441-4. |
| [35] | Gorgun G, Samur MK, Cowens KB, Paula S, Bianchi G, Anderson JE, et al. Lenalidomide Enhances Immune Checkpoint Blockade-Induced Immune Response in Multiple Myeloma. Clin Cancer Res. 2015; 21 (20): 4607-18. |
| [36] | Benson DM, Jr., Bakan CE, Mishra A, Hofmeister CC, Efebera Y, Becknell B, et al. The PD-1/PD-L1 axis modulates the natural killer cell versus multiple myeloma effect: a therapeutic target for CT-011, a novel monoclonal anti-PD-1 antibody. Blood. 2010; 116 (13): 2286-94. |
| [37] | Suen H, Brown R, Yang S, Ho PJ, Gibson J, Joshua D. The failure of immune checkpoint blockade in multiple myeloma with PD-1 inhibitors in a phase 1 study. Leukemia. 2015; 29 (7): 1621-2. |
| [38] | Miguel JS, Mateos M-V, Shah JJ, Ocio EM, Rodriguez-Otero P, Reece D, et al. Pembrolizumab in Combination with Lenalidomide and Low-Dose Dexamethasone for Relapsed/Refractory Multiple Myeloma (RRMM): Keynote-023. Blood. 2015; 126 (23): 505. |
| [39] | Wilson L, Cohen AD, Weiss BM, Vogl DT, Garfall AL, Capozzi DL, et al. Pembrolizumab in Combination with Pomalidomide and Dexamethasone (PEMBRO/POM/DEX) for Pomalidomide Exposed Relapsed or Refractory Multiple Myeloma. 2016; 128 (22): 2119-. |
| [40] | Badros A, Hyjek E, Ma N, Lesokhin A, Dogan A, Rapoport AP, et al. Pembrolizumab, pomalidomide, and low-dose dexamethasone for relapsed/refractory multiple myeloma. Blood. 2017; 130 (10): 1189-97. |
| [41] | Fevery S, Billiau AD, Sprangers B, Rutgeerts O, Lenaerts C, Goebels J, et al. CTLA-4 blockade in murine bone marrow chimeras induces a host-derived antileukemic effect without graft-versus-host disease. Leukemia. 2007; 21 (7): 1451-9. |
| [42] | Blazar B, Taylor P, Panoskaltsis-Mortari A, Gray G, Vallera D. Coblockade of the LFA1: ICAM and CD28/CTLA4: B7 pathways is a highly effective means of preventing acute lethal graft-versus-host disease induced by fully major histocompatibility complex-disparate donor grafts. 1995; 85 (9): 2607-18. |
| [43] | Yang H, Bueso-Ramos C, DiNardo C, Estecio MR, Davanlou M, Geng QR, et al. Expression of PD-L1, PD-L2, PD-1 and CTLA4 in myelodysplastic syndromes is enhanced by treatment with hypomethylating agents. Leukemia. 2014; 28 (6): 1280-8. |
| [44] | Graf M, Reif S, Hecht K, Pelka-Fleischer R, Kroell T, Pfister K, et al. High expression of costimulatory molecules correlates with low relapse-free survival probability in acute myeloid leukemia (AML). Ann Hematol. 2005; 84 (5): 287-97. |
| [45] | Zhang L, Gajewski TF, Kline J. PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model. Blood. 2009; 114 (8): 1545-52. |
| [46] | Haroun F, Solola SA, Nassereddine S, Tabbara I. PD-1 signaling and inhibition in AML and MDS. Ann Hematol. 2017; 96 (9): 1441-8. |
| [47] | Kronig H, Kremmler L, Haller B, Englert C, Peschel C, Andreesen R, et al. Interferon-induced programmed death-ligand 1 (PD-L1/B7-H1) expression increases on human acute myeloid leukemia blast cells during treatment. Eur J Haematol. 2014; 92 (3): 195-203. |
| [48] | Youngblood B, Oestreich KJ, Ha SJ, Duraiswamy J, Akondy RS, West EE, et al. Chronic virus infection enforces demethylation of the locus that encodes PD-1 in antigen-specific CD8(+) T cells. Immunity. 2011; 35 (3): 400-12. |
| [49] | Daver NG, Basu S, Garcia-Manero G, Cortes JE, Ravandi F, Jabbour E, et al. Phase IB/II study of nivolumab with azacytidine (AZA) in patients (pts) with relapsed AML. J Clin Oncol. 2017; 35. |
| [50] | Dutt S, Tseng D, Ermann J, George TI, Liu YP, Davis CR, et al. Naive and memory T cells induce different types of graft-versus-host disease. J Immunol. 2007; 179 (10): 6547-54. |
| [51] | Alho AC, Kim HT, Chammas MJ, Reynolds CG, Matos TR, Forcade E, et al. Unbalanced recovery of regulatory and effector T cells after allogeneic stem cell transplantation contributes to chronic GVHD. Blood. 2016; 127 (5): 646-57. |
| [52] | Saha A, Aoyama K, Taylor PA, Koehn BH, Veenstra RG, Panoskaltsis-Mortari A, et al. Host programmed death ligand 1 is dominant over programmed death ligand 2 expression in regulating graft-versus-host disease lethality. Blood. 2013; 122 (17): 3062-73. |
| [53] | Saha A, O'Connor RS, Thangavelu G, Lovitch SB, Dandamudi DB, Wilson CB, et al. Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality. J Clin Invest. 2016; 126 (7): 2642-60. |
| [54] | Bashey A, Medina B, Corringham S, Pasek M, Carrier E, Vrooman L, et al. CTLA4 blockade with ipilimumab to treat relapse of malignancy after allogeneic hematopoietic cell transplantation. Blood. 2009; 113 (7): 1581-8. |
| [55] | Davids MS, Kim HT, Bachireddy P, Costello C, Liguori R, Savell A, et al. Ipilimumab for Patients with Relapse after Allogeneic Transplantation. N Engl J Med. 2016; 375 (2): 143-53. |
| [56] | Herbaux C, Gauthier J, Brice P, Drumez E, Ysebaert L, Doyen H, et al. Efficacy and tolerability of nivolumab after allogeneic transplantation for relapsed Hodgkin lymphoma. Blood. 2017; 129 (18): 2471-8. |
| [57] | Angenendt L, Schliemann C, Lutz M, Rebber E, Schulze AB, Weckesser M, et al. Nivolumab in a patient with refractory Hodgkin's lymphoma after allogeneic stem cell transplantation. Bone Marrow Transplant. 2016; 51 (3): 443-5. |
| [58] | Herrera AF, Chen L, Popplewell LL, Budde LE, Mei M, Armenian SH, et al. Preliminary Results from a Phase I Trial of Pembrolizumab Plus Vorinostat in Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma, Follicular Lymphoma, and Hodgkin Lymphoma. Blood. 2019; 134 (Supplement_1): 759. doi: 10.1182/blood-2019-123163. |
APA Style
Shukaib Arslan, Alex Herrera, Monzr Al Malki. (2021). The Landscape of Checkpoint Inhibition in the Management of Hematological Malignancies. Cancer Research Journal, 9(2), 122-130. https://doi.org/10.11648/j.crj.20210902.16
ACS Style
Shukaib Arslan; Alex Herrera; Monzr Al Malki. The Landscape of Checkpoint Inhibition in the Management of Hematological Malignancies. Cancer Res. J. 2021, 9(2), 122-130. doi: 10.11648/j.crj.20210902.16
AMA Style
Shukaib Arslan, Alex Herrera, Monzr Al Malki. The Landscape of Checkpoint Inhibition in the Management of Hematological Malignancies. Cancer Res J. 2021;9(2):122-130. doi: 10.11648/j.crj.20210902.16
Share This Article
Twitter
Linked In
Facebook
Copy
Download@article{10.11648/j.crj.20210902.16,
author = {Shukaib Arslan and Alex Herrera and Monzr Al Malki},
title = {The Landscape of Checkpoint Inhibition in the Management of Hematological Malignancies},
journal = {Cancer Research Journal},
volume = {9},
number = {2},
pages = {122-130},
doi = {10.11648/j.crj.20210902.16},
url = {https://doi.org/10.11648/j.crj.20210902.16},
eprint = {https://article.sciencepublishinggroup.com/pdf/10.11648.j.crj.20210902.16},
abstract = {The programmed-death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) pathways are inhibitory immune checkpoints involved in the escape of cancer cells from the immune system. Inhibition of these immune checkpoints can lead to the induction of body’s immune response to these cancer cells. To activate the immune system against the tumor cells, various monoclonal antibodies targeting these pathways have been developed. Many of such antibodies have been approved for therapy in solid tumor malignancies and now some hematological malignancies. Here, we review the available data regarding the response to PD-1 and CTLA-4 pathway blockade in hematological malignancies including Hodgin lymphoma, non-Hodgkin lymhoma, multiple myeloma and myeloid neoplasms as well as before and after hematopoietic cell transplantation. We also discuss the specific concerns and differences related to their use in hematological malignancies (HMs) as compared to solid tumors.},
year = {2021}
}
TY - JOUR T1 - The Landscape of Checkpoint Inhibition in the Management of Hematological Malignancies AU - Shukaib Arslan AU - Alex Herrera AU - Monzr Al Malki Y1 - 2021/06/30 PY - 2021 N1 - https://doi.org/10.11648/j.crj.20210902.16 DO - 10.11648/j.crj.20210902.16 T2 - Cancer Research Journal JF - Cancer Research Journal JO - Cancer Research Journal SP - 122 EP - 130 PB - Science Publishing Group SN - 2330-8214 UR - https://doi.org/10.11648/j.crj.20210902.16 AB - The programmed-death 1 (PD-1) and cytotoxic T-lymphocyte associated protein 4 (CTLA-4) pathways are inhibitory immune checkpoints involved in the escape of cancer cells from the immune system. Inhibition of these immune checkpoints can lead to the induction of body’s immune response to these cancer cells. To activate the immune system against the tumor cells, various monoclonal antibodies targeting these pathways have been developed. Many of such antibodies have been approved for therapy in solid tumor malignancies and now some hematological malignancies. Here, we review the available data regarding the response to PD-1 and CTLA-4 pathway blockade in hematological malignancies including Hodgin lymphoma, non-Hodgkin lymhoma, multiple myeloma and myeloid neoplasms as well as before and after hematopoietic cell transplantation. We also discuss the specific concerns and differences related to their use in hematological malignancies (HMs) as compared to solid tumors. VL - 9 IS - 2 ER -
Email: