A pilot study of activity of pembrolizumab and low dose chemotherapy in relapsed/refractory T-cell lymphoma: Jordanian experience
Keywords:
Peripheral T-cell lymphoma; Pembrolizumab; Immunotherapy; chemotherapyAbstract
Background and aim: Peripheral T-cell lymphomas (PTCLs) are associated with poor prognosis and limited treatment options in the relapsed/refractory (R/R) setting. Programmed cell death-1 and ligand-1 (PD-1 and PD-L1) are frequently expressed in T-cell Lymphoma. It provides a rationale for using immune checkpoint inhibitors (ICIs) to manage PTCLs. Many studies in solid tumors showed higher efficacy of ICIs when used in combination with chemotherapy. Methods: A study of 11 patients with R/R PTCLs was conducted retrospectively. They were treated at two Jordanian hospitals with Pembrolizumab, Vincristine, and Cyclophosphamide every three weeks. Results: The overall response rate (ORR) was 63%, with three complete responses (CR) and four partial responses (PR). The median progression-free survival (PFS) was 4.0 months (95% CI: 1.7 to 11.4), and the median overall survival (OS) was 17.0 months (95% CI: 0.7 to 33.2). Conclusions: Pembrolizumab and low-dose chemotherapy demonstrated promising activity in R/R PTCL, with high response rates. Furthermore, extensive studies are needed to define the role of such an approach.
References
Vose J, Armitage J, Weisenburger D, International TCLP. International peripheral T-cell and natural killer/T-cell lymphoma study: pathology findings and clinical outcomes. J Clin Oncol. 2008;26(25):4124-30.doi:10.1200/JCO.2008.16.4558.
Swerdlow SH, Campo E, Pileri SA, et al. The 2016 revision of the World Health Organization classification of lymphoid neoplasms. Blood. 2016;127(20):2375-90.doi:10.1182/blood-2016-01-643569.
Yoon SE, Song Y, Kim SJ, et al. Comprehensive analysis of peripheral T-cell and natural killer/T-cell lymphoma in Asian patients: A multinational, multicenter, prospective registry study in Asia. Lancet Reg Health West Pac. 2021;10:100126.doi:10.1016/j.lanwpc.2021.100126.
Liu W, Ji X, Song Y, et al. Improving survival of 3760 patients with lymphoma: Experience of an academic center over two decades. Cancer Med. 2020;9(11):3765-74.doi:10.1002/cam4.3037.
Mak V, Hamm J, Chhanabhai M, et al. Survival of patients with peripheral T-cell lymphoma after first relapse or progression: spectrum of disease and rare long-term survivors. J Clin Oncol. 2013;31(16):1970-6.doi:10.1200/JCO.2012.44.7524.
Bennani NN, Ansell SM. Tumor Microenvironment in T-Cell Lymphomas. Cancer Treat Res. 2019;176:69-82.doi:10.1007/978-3-319-99716-2_3.
Wilcox RA, Wada DA, Ziesmer SC, et al. Monocytes promote tumor cell survival in T-cell lymphoproliferative disorders and are impaired in their ability to differentiate into mature dendritic cells. Blood. 2009;114(14):2936-44.doi:10.1182/blood-2009-05-220111.
Tsushima F, Yao S, Shin T, et al. Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy. Blood. 2007;110(1):180-5.doi:10.1182/blood-2006-11-060087.
Wilcox RA, Feldman AL, Wada DA, et al. B7-H1 (PD-L1, CD274) suppresses host immunity in T-cell lymphoproliferative disorders. Blood. 2009;114(10):2149-58.doi:10.1182/blood-2009-04-216671.
Strome SE, Dong H, Tamura H, et al. B7-H1 blockade augments adoptive T-cell immunotherapy for squamous cell carcinoma. Cancer Res. 2003;63(19):6501-5.
Green MR, Monti S, Rodig SJ, 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.doi:10.1182/blood-2010-05-282780.
Ansell SM, Lesokhin AM, Borrello I, et al. PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma. N Engl J Med. 2015;372(4):311-9.doi:10.1056/NEJMoa1411087.
Ansell SM. Nivolumab in the Treatment of Hodgkin Lymphoma. Clin Cancer Res. 2017;23(7):1623-6.doi:10.1158/1078-0432.CCR-16-1387.
Lesokhin AM, Ansell SM, Armand P, 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. doi:10.1200/JCO.2015.65.9789.
Xia Y, Jeffrey Medeiros L, Young KH. Signaling pathway and dysregulation of PD1 and its ligands in lymphoid malignancies. Biochim Biophys Acta. 2016;1865(1):58-71.doi:10.1016/j.bbcan.2015.09.002.
Merryman RW, Armand P, Wright KT, Rodig SJ. Checkpoint blockade in Hodgkin and non-Hodgkin lymphoma. Blood Adv. 2017;1(26):2643-54.doi:10.1182/bloodadvances.2017012534.
Bennani NN, Kim HJ, Pederson LD, et al. Nivolumab in patients with relapsed or refractory peripheral T-cell lymphoma: modest activity and cases of hyperprogression. J Immunother Cancer. 2022 Jun;10(6):e004984. doi: 10.1136/jitc-2022-004984.
Barta SK, Zain J, MacFarlane AWt, et al. Phase II Study of the PD-1 Inhibitor Pembrolizumab for the Treatment of Relapsed or Refractory Mature T-cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2019;19(6):356-64 e3.doi:10.1016/j.clml.2019.03.022.
Kwong YL, Chan TSY, Tan D, 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.doi:10.1182/blood-2016-12-756841.
Li X, Cheng Y, Zhang M, et al. Activity of pembrolizumab in relapsed/refractory NK/T-cell lymphoma. J Hematol Oncol. 2018;11(1):15.doi:10.1186/s13045-018-0559-7.
Cheson BD, Pfistner B, Juweid ME, et al. Revised response criteria for malignant lymphoma. J Clin Oncol. 2007;25(5):579-86.doi:10.1200/JCO.2006.09.2403.
Fournier L, Ammari S, Thiam R, Cuenod CA. Imaging criteria for assessing tumour response: RECIST, mRECIST, Cheson. Diagn Interv Imaging. 2014;95(7-8):689-703.doi:10.1016/j.diii.2014.05.002.
Coiffier B, Pro B, Prince HM, et al. Results from a pivotal, open-label, phase II study of romidepsin in relapsed or refractory peripheral T-cell lymphoma after prior systemic therapy. J Clin Oncol. 2012;30(6):631-6.doi:10.1200/JCO.2011.37.4223.
O'Connor OA, Horwitz S, Masszi T, et al. Belinostat in Patients With Relapsed or Refractory Peripheral T-Cell Lymphoma: Results of the Pivotal Phase II BELIEF (CLN-19) Study. J Clin Oncol. 2015;33(23):2492-9.doi:10.1200/JCO.2014.59.2782.
O'Connor OA, Pro B, Pinter-Brown L, et al. Pralatrexate in patients with relapsed or refractory peripheral T-cell lymphoma: results from the pivotal PROPEL study. J Clin Oncol. 2011;29(9):1182-9.doi:10.1200/JCO.2010.29.9024.
Bennani NN, Kim HJ, Pederson LD, et al. Nivolumab in patients with relapsed or refractory peripheral T-cell lymphoma: modest activity and cases of hyperprogression. J Immunother Cancer. 2022;10(6).doi:10.1136/jitc-2022-004984.
Downloads
Published
Issue
Section
License
Copyright (c) 2024 Salah Abbasi, Haytham Dwaik, Layla Abbasi, Huda Al Hourani
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Transfer of Copyright and Permission to Reproduce Parts of Published Papers.
Authors retain the copyright for their published work. No formal permission will be required to reproduce parts (tables or illustrations) of published papers, provided the source is quoted appropriately and reproduction has no commercial intent. Reproductions with commercial intent will require written permission and payment of royalties.