Sustained Yet Non-curative Response to Lenalidomide in Relapsed Angioimmunoblastic T-cell Lymphoma with Acquired Chidamide Resistance: a Case Report with 10-year Follow-up, Genetic Insights and Literature Review

Overview

Journal Front Oncol

Specialty Oncology

Date 2024 Dec 12

PMID 39664198

Authors

Juan Xu

Jie Huang

Liping Xie

Ting Liu

Jianjun Li

Xinchuan Chen

Zhigang Liu

Sha Zhao

Caigang Xu

Yu Wu

Affiliations

Soon will be listed here.

Abstract

Angioimmunoblastic T-cell lymphoma (AITL) is an aggressive subtype of peripheral T-cell lymphoma (PTCL) characterized by its T-follicular helper (TFH) phenotype. Relapsed and refractory disease is common in AITL and often associated with a poor prognosis. The presence of epigenetic abnormalities, immune dysregulation, hyperinflammation and active angiogenesis in AITL offers potential targets for histone deacetylase (HDAC) inhibitors and immunomodulatory drugs (IMiDs). Herein, we present a case of AITL with multiple relapses over a decade. Following intensive chemotherapy and autologous stem cell transplantation (ASCT), the patient relapsed with extensive nodal and extranodal involvement, particularly pulmonary lesions, and subsequently pursued chemo-free treatments. Initially, the patient exhibited a remarkable response to single-agent chidamide, the first oral HDAC inhibitor. Soon after developing resistance to chidamide, continuous treatment with lenalidomide led to an impressive sustained complete remission lasting 64 months, followed by a diminished response for an additional 11 months. Genetic profiling of the patient revealed mutations in KMT2D and ARID1A, along with chromosomal aberrations such as del(5q). Notably, genes commonly mutated in AITL, including RHOA, TET2, DNMT3A, and IDH2, were absent in this case. A review of the literature highlights the heterogeneous genomic landscape of AITL and the diversity of treatment options available, underscoring the importance of tailored approaches to overcome resistance and improve outcomes in this distinct lymphoma subtype.

References

Sawhney R, Volkmer 2nd R, Cooper B . Relapsed angioimmunoblastic T-cell lymphoma with large pericardial effusion. Proc (Bayl Univ Med Cent). 2020; 33(1):62-64. PMC: 6988641. DOI: 10.1080/08998280.2019.1668720. View

Wei C, Li W, Qin L, Liu S, Xue C, Ren K . Clinicopathologic characteristics, outcomes, and prognostic factors of angioimmunoblastic T-cell lymphoma in China. Cancer Med. 2022; 12(4):3987-3998. PMC: 9972121. DOI: 10.1002/cam4.5248. View

Morschhauser F, Fitoussi O, Haioun C, Thieblemont C, Quach H, Delarue R . A phase 2, multicentre, single-arm, open-label study to evaluate the safety and efficacy of single-agent lenalidomide (Revlimid) in subjects with relapsed or refractory peripheral T-cell non-Hodgkin lymphoma: the EXPECT trial. Eur J Cancer. 2013; 49(13):2869-76. DOI: 10.1016/j.ejca.2013.04.029. View

Xie C, Li X, Zeng H, Qian W . Molecular insights into pathogenesis and targeted therapy of peripheral T cell lymphoma. Exp Hematol Oncol. 2020; 9(1):30. PMC: 7664070. DOI: 10.1186/s40164-020-00188-w. View

Palomero T, Couronne L, Khiabanian H, Kim M, Ambesi-Impiombato A, Perez-Garcia A . Recurrent mutations in epigenetic regulators, RHOA and FYN kinase in peripheral T cell lymphomas. Nat Genet. 2014; 46(2):166-70. PMC: 3963408. DOI: 10.1038/ng.2873. View

Zhu Y, Shi C, Bruins L, Wang X, Riggs D, Porter B . Identification of lenalidomide resistance pathways in myeloma and targeted resensitization using cereblon replacement, inhibition of STAT3 or targeting of IRF4. Blood Cancer J. 2019; 9(2):19. PMC: 6370766. DOI: 10.1038/s41408-019-0173-0. View

Xu J, Tang Y, Zhao S, Zhang W, Xiu Y, Liu T . Angioimmunoblastic T-cell lymphoma with coexisting plasma cell myeloma: a case report and review of the literature. Tohoku J Exp Med. 2015; 235(4):283-8. DOI: 10.1620/tjem.235.283. View

Mikhail F, Biegel J, Cooley L, Dubuc A, Hirsch B, Horner V . Technical laboratory standards for interpretation and reporting of acquired copy-number abnormalities and copy-neutral loss of heterozygosity in neoplastic disorders: a joint consensus recommendation from the American College of Medical Genetics and.... Genet Med. 2019; 21(9):1903-1916. DOI: 10.1038/s41436-019-0545-7. View

Chiba S, Sakata-Yanagimoto M . Advances in understanding of angioimmunoblastic T-cell lymphoma. Leukemia. 2020; 34(10):2592-2606. PMC: 7376827. DOI: 10.1038/s41375-020-0990-y. View

10.

Alaggio R, Amador C, Anagnostopoulos I, Attygalle A, de Oliveira Araujo I, Berti E . The 5th edition of the World Health Organization Classification of Haematolymphoid Tumours: Lymphoid Neoplasms. Leukemia. 2022; 36(7):1720-1748. PMC: 9214472. DOI: 10.1038/s41375-022-01620-2. View

11.

Broccoli A, Zinzani P . Angioimmunoblastic T-Cell Lymphoma. Hematol Oncol Clin North Am. 2017; 31(2):223-238. DOI: 10.1016/j.hoc.2016.12.001. View

12.

Haertle L, Barrio S, Munawar U, Han S, Zhou X, Vogt C . Cereblon enhancer methylation and IMiD resistance in multiple myeloma. Blood. 2021; 138(18):1721-1726. PMC: 8569411. DOI: 10.1182/blood.2020010452. View

13.

Okuyama S, Terada T, Kumagai H, Tsumanuma R, Omoto E, Ueki T . Epstein-Barr virus clonality and plasmacytosis in a patient with atypical angioimmunoblastic T cell lymphoma. Ann Hematol. 2017; 97(3):537-539. DOI: 10.1007/s00277-017-3189-1. View

14.

Toumishey E, Prasad A, Dueck G, Chua N, Finch D, Johnston J . Final report of a phase 2 clinical trial of lenalidomide monotherapy for patients with T-cell lymphoma. Cancer. 2014; 121(5):716-23. DOI: 10.1002/cncr.29103. View

15.

Federico M, Rudiger T, Bellei M, Nathwani B, Luminari S, Coiffier B . Clinicopathologic characteristics of angioimmunoblastic T-cell lymphoma: analysis of the international peripheral T-cell lymphoma project. J Clin Oncol. 2012; 31(2):240-6. PMC: 3532394. DOI: 10.1200/JCO.2011.37.3647. View

16.

Gooding S, Ansari-Pour N, Towfic F, Estevez M, Chamberlain P, Tsai K . Multiple cereblon genetic changes are associated with acquired resistance to lenalidomide or pomalidomide in multiple myeloma. Blood. 2021; 137(2):232-237. PMC: 7893409. DOI: 10.1182/blood.2020007081. View

17.

Advani R, Skrypets T, Civallero M, Spinner M, Manni M, Kim W . Outcomes and prognostic factors in angioimmunoblastic T-cell lymphoma: final report from the international T-cell Project. Blood. 2021; 138(3):213-220. PMC: 8493974. DOI: 10.1182/blood.2020010387. View

18.

Chan T, Tse E, Kwong Y . Chidamide in the treatment of peripheral T-cell lymphoma. Onco Targets Ther. 2017; 10:347-352. PMC: 5238768. DOI: 10.2147/OTT.S93528. View

19.

Fabbri A, Cencini E, Pietrini A, Gozzetti A, Defina M, Fontanelli G . Impressive activity of lenalidomide monotherapy in refractory angioimmunoblastic T-cell lymphoma: report of a case with long-term follow-up. Hematol Oncol. 2012; 31(4):213-7. DOI: 10.1002/hon.2038. View

20.

Yoon S, Cho J, Kim Y, Ko Y, Park W, Kim S . Comprehensive analysis of clinical, pathological, and genomic characteristics of follicular helper T-cell derived lymphomas. Exp Hematol Oncol. 2021; 10(1):33. PMC: 8120779. DOI: 10.1186/s40164-021-00224-3. View