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

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, im...

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Main Authors: Juan Xu, Jie Huang, Liping Xie, Ting Liu, Jianjun Li, Xinchuan Chen, Zhigang Liu, Sha Zhao, Caigang Xu, Yu Wu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Oncology
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Online Access:https://www.frontiersin.org/articles/10.3389/fonc.2024.1471090/full
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author Juan Xu
Jie Huang
Liping Xie
Ting Liu
Jianjun Li
Xinchuan Chen
Zhigang Liu
Sha Zhao
Caigang Xu
Caigang Xu
Yu Wu
author_facet Juan Xu
Jie Huang
Liping Xie
Ting Liu
Jianjun Li
Xinchuan Chen
Zhigang Liu
Sha Zhao
Caigang Xu
Caigang Xu
Yu Wu
author_sort Juan Xu
collection DOAJ
description 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.
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spelling doaj-art-ddf2444d1ffc45b69f7eb43d69e321cf2024-11-27T06:33:16ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2024-11-011410.3389/fonc.2024.14710901471090Sustained 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 reviewJuan Xu0Jie Huang1Liping Xie2Ting Liu3Jianjun Li4Xinchuan Chen5Zhigang Liu6Sha Zhao7Caigang Xu8Caigang Xu9Yu Wu10Department of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Pathology, West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaChengdu Shang Jin Nan Fu Hospital / Shang Jin Hospital of West China Hospital, Sichuan University, Chengdu, ChinaDepartment of Hematology, Institute of Hematology, West China Hospital, Sichuan University, Chengdu, ChinaAngioimmunoblastic 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.https://www.frontiersin.org/articles/10.3389/fonc.2024.1471090/fullangioimmunoblastic T-cell lymphomarelapsedlenalidomidechidamideresistanceimmune dysregulation
spellingShingle Juan Xu
Jie Huang
Liping Xie
Ting Liu
Jianjun Li
Xinchuan Chen
Zhigang Liu
Sha Zhao
Caigang Xu
Caigang Xu
Yu Wu
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
Frontiers in Oncology
angioimmunoblastic T-cell lymphoma
relapsed
lenalidomide
chidamide
resistance
immune dysregulation
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic angioimmunoblastic T-cell lymphoma
relapsed
lenalidomide
chidamide
resistance
immune dysregulation
url https://www.frontiersin.org/articles/10.3389/fonc.2024.1471090/full
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