Durable clinical remission induced by romidepsin for chemotherapy-refractory peripheral T-cell lymphoma with central nervous system involvement

Chan, Kah Lok; Weyden, Carrie van der; Khoo, Christine; Lade, Stephen; Blombery, Piers; Westerman, David; Khot, Amit; Melo, Brian; Johnstone, Ricky W.; Prince, H. Miles; Dickinson, Michael

doi:10.1080/10428194.2016.1222375

Cited by 12 publications

(4 citation statements)

References 15 publications

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“…Histone deacetylase inhibitors (HDACIs) have shown good efficacy in various types of intracranial metastatic tumors. In cases of refractory peripheral T-cell lymphoma with CNS metastasis, romidepsin achieves durable clinical remission ( 114 ). Patients with brain metastases from non-small cell lung cancer were treated with chidamide combined with paclitaxel and carboplatin, and 40% of patients achieved complete intracranial response after treatment ( 115 ).…”

Section: Treatmentmentioning

confidence: 99%

Relapsed Primary Central Nervous System Lymphoma: Current Advances

2021

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Primary central nervous system lymphoma is an invasive malignant lymphoma confined to the central nervous system. Although patients undergoing first-line treatment can achieve complete response, most of them still relapse within two years. Relapsed lymphoma is derived from occult lymphoma cells, and B cell receptor pathway activation and immune escape are the key mechanisms for the pathogenesis of PCNSL. Most relapses are in the central nervous system, a small number of relapses are isolated systemic relapses, and clinical symptoms occur early and vary. Current treatments for relapse include high-dose methotrexate rechallenge and other regimens of chemotherapy, whole-brain radiation therapy, hematopoietic stem-cell transplantation, targeted therapy and immunotherapy, which have become promising treatments. The overall prognosis of relapsed PCNSL is very poor, although it is affected by many factors. This article summarizes the mechanisms, related factors, clinical features, follow-up, treatment and prognosis of relapsed primary central nervous system lymphoma.

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Section: Treatmentmentioning

confidence: 99%

Relapsed Primary Central Nervous System Lymphoma: Current Advances

2021

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“…Romidepsin is a typical cyclic depsipeptide class HDACi that has a primarily inhibitory effect on class I HDACs (HDAC1, HDAC2, and HDAC3) and a weak effect on class IIB HDACs (HDAC6). Romidepsin is a more effective single-agent therapy that induces durable responses in relapsed/refractory PTCL patients who have received at least 1 prior systemic therapy, and regardless of age [ 48 , 62 – 65 ]. In one pivotal open-label, phase II study of romidepsin treatment in 130 relapsed or refractory peripheral T-cell lymphoma patients after prior systemic therapy, single-agent romidepsin induced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across all major PTCL subtypes, regardless of the number or type of prior therapies [ 66 ].…”

Section: Epigenetic Drugs In Relapsed and Refractory Ptclmentioning

confidence: 99%

Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma

Zhang

2020

Clin Epigenet

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Peripheral T-cell lymphoma (PTCL) is a rare and heterogeneous group of clinically aggressive diseases associated with poor prognosis. Except for ALK + anaplastic large-cell lymphoma (ALCL), most peripheral T-cell lymphomas are highly malignant and have an aggressive disease course and poor clinical outcomes, with a poor remission rate and frequent relapse after first-line treatment. Aberrant epigenetic alterations play an important role in the pathogenesis and development of specific types of peripheral T-cell lymphoma, including the regulation of the expression of genes and signal transduction. The most common epigenetic alterations are DNA methylation and histone modification. Histone modification alters the level of gene expression by regulating the acetylation status of lysine residues on the promoter surrounding histones, often leading to the silencing of tumour suppressor genes or the overexpression of proto-oncogenes in lymphoma. DNA methylation refers to CpG islands, generally leading to tumour suppressor gene transcriptional silencing. Genetic studies have also shown that some recurrent mutations in genes involved in the epigenetic machinery, including TET2, IDH2-R172, DNMT3A, RHOA, CD28, IDH2, TET2, MLL2, KMT2A, KDM6A, CREBBP, and EP300, have been observed in cases of PTCL. The aberrant expression of miRNAs has also gradually become a diagnostic biomarker. These provide a reasonable molecular mechanism for epigenetic modifying drugs in the treatment of PTCL. As epigenetic drugs implicated in lymphoma have been continually reported in recent years, many new ideas for the diagnosis, treatment, and prognosis of PTCL originate from epigenetics in recent years. Novel epigenetic-targeted drugs have shown good tolerance and therapeutic effects in the treatment of peripheral T-cell lymphoma as monotherapy or combination therapy. NCCN Clinical Practice Guidelines also recommended epigenetic drugs for PTCL subtypes as second-line therapy. Epigenetic mechanisms provide new directions and therapeutic strategies for the research and treatment of peripheral T-cell lymphoma. Therefore, this paper mainly reviews the epigenetic changes in the pathogenesis of peripheral T-cell lymphoma and the advancement of epigenetic-targeted drugs in the treatment of peripheral T-cell lymphoma (PTCL).

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“…Histone deacetylase inhibitors (HDAC inhibitors) have recently been investigated as possible cancer therapies and have shown promising outcomes in several types of tumors. Durable clinical remission using romidepsin has been achieved in a refractory peripheral T-cell lymphoma case with CNS involvement [137]. Patients with cerebral metastasis of non–small-cell lung cancer were given chidamide combined with paclitaxel and carboplatin, and complete disappearance of the metastatic tumor after chemotherapy was observed [138].…”

Section: Treatment Advancesmentioning

confidence: 99%

Primary Central Nervous System Lymphoma: Molecular Pathogenesis and Advances in Treatment

Cai

Young

2019

Translational Oncology

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Primary central nervous system lymphoma (PCNSL) is a group of extranodal non-Hodgkin lymphoma that exhibits specific biological characteristics and clinical behavior, with an aggressive disease course and unsatisfactory patient outcomes. It is of great importance to identify aberrant genetic loci and important molecular pathways that might suggest potential targets for new therapeutics and provide prognostic information. In this review, we listed various genetic and epigenetic alterations that are involved in PCNSL pathogenesis. In the aspect of treatment, we summarized the related literatures and evaluated the efficacy of surgery, induction chemotherapy, radiotherapy, intrathecal chemotherapy, and autologous stem cell transplantation in PCNSL. We also proposed the possible new agents for recurrent and relapse PCNSL based on the result of recent clinical researches.

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Durable clinical remission induced by romidepsin for chemotherapy-refractory peripheral T-cell lymphoma with central nervous system involvement

Cited by 12 publications

References 15 publications

Relapsed Primary Central Nervous System Lymphoma: Current Advances

Relapsed Primary Central Nervous System Lymphoma: Current Advances

Epigenetic alterations and advancement of treatment in peripheral T-cell lymphoma

Primary Central Nervous System Lymphoma: Molecular Pathogenesis and Advances in Treatment

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