Controversies in the Treatment of Peripheral T-cell Lymphoma.
Ontology highlight
ABSTRACT:
SUBMITTER: Bachy E
PROVIDER: S-EPMC7469987 | biostudies-literature | 2020 Oct
REPOSITORIES: biostudies-literature
Publications
Controversies in the Treatment of Peripheral T-cell Lymphoma.
Bachy Emmanuel E Broccoli Alessandro A Dearden Claire C de Leval Laurence L Gaulard Philippe P Koch Raphael R Morschhauser Franck F Trümper Lorenz L Zinzani Pier Luigi PL
HemaSphere 20200901 5
Peripheral T-cell lymphomas are a heterogeneous group of rare diseases with an aggressive behavior and dismal prognosis. Their classification is complex and still evolving, and several biomolecular markers now help refine the prognosis of specific disease entities, although still have limited impact in tailoring the treatment. First-line treatment strategies can cure only a minority of patients and relapsed-refractory disease still represents the major cause of failure. Frontline autologous tran ...[more]
Similar Datasets
Project description:Systemic peripheral T cell lymphomas (PTCL) are a rare and clinically and biologically heterogeneous group of disorders with scarce and generally low-quality evidence guiding their management. In this manuscript, we tackle the current controversies in the front-line treatment of systemic PTCL including (1) whether CNS prophylaxis should be administered; (2) whether CHOEP should be preferred over CHOP; (3) what role brentuximab vedotin should have; (4) whether stem cell transplant (SCT) consolidation should be used and whether autologous or allogeneic; (5) how should molecular subtypes (including DUSP22 or TP63-rearranged ALCL or GATA3 or TBX21 PTCL, NOS) impact therapeutic decisions; and (6) whether there is a role for targeted agents beyond brentuximab vedotin.
| S-EPMC9818471 | biostudies-literature
Project description:UnlabelledPeripheral T-cell lymphoma (PTCL) is a heterogeneous group of non-Hodgkin lymphomas associated with poor prognosis in most subtypes. Diagnosis of this rare disease by expert hematopathologists improves accuracy of subtyping, and referral to academic or specialty centers is recommended. Many patients, however, will receive treatment in the community, and knowledge of approved agents is key to optimizing therapeutic approaches for all patients. There is no current standard of care for patients with PTCL and no approved therapies for first-line treatment. Although many patients initially respond to induction chemotherapy, responses are often brief, and many patients relapse or become treatment refractory. For patients with relapsed or refractory PTCL, achievement of durable responses is challenging, and there are few treatment options. Romidepsin is a histone deacetylase inhibitor approved by the U.S. Food and Drug Administration for the treatment of patients with cutaneous T-cell lymphoma who have received one prior systemic therapy or more and patients with PTCL who have received one prior therapy or more. Approval of romidepsin for PTCL was based on a pivotal phase II study of patients with relapsed or refractory PTCL (n = 131) that demonstrated an objective response rate of 25% including 15% with complete response; responses lasted a median of >2 years. Long-term responses to romidepsin were achieved in patients regardless of baseline characteristics, including subtype, heavy pretreatment, response to prior therapy, or advanced disease. Common adverse events included hematologic abnormalities, gastrointestinal or asthenic conditions, and infections; romidepsin was not correlated with clinically meaningful QT prolongation or electrocardiogram abnormalities.Implications for practiceDue to the rarity, severity, and heterogeneous nature of peripheral T-cell lymphoma (PTCL), diagnosis by expert hematopathologists is preferred, and referral to specialty centers is recommended. Many patients, however, will receive treatment in the community, and community oncologists play a key role in the recognition and treatment of PTCL. Knowledge of approved agents is key for optimizing therapeutic approaches. This review provides an overview of PTCL and an in-depth examination of romidepsin, a histone deacetylase inhibitor approved for the treatment of relapsed or refractory PTCL, and highlights difficulties of diagnosis and optimization of treatment modalities for patients with PTCL.
| S-EPMC4571813 | biostudies-literature
Project description:Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of clinically aggressive diseases associated with poor outcome. Despite progress in the last several years, resulting in a deeper understanding of the natural history and biology of PTCL based on molecular profiling and next-generation sequencing, there is a need for improvement in efficacy of chemotherapeutic regimens for newly diagnosed patients. Treatment in the front-line setting is most often cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens, which are associated with a high failure rate and frequent relapses. Trials evaluating intensive chemotherapy have resulted in variable success in prolonging event-free survival, but overall survival has remained unchanged. Furthermore, this strategy is limited to patients who are in complete remission after initial anthracycline-based chemotherapy. Many patients are ineligible for hematopoietic stem cell transplantation because of age or failure to achieve remission. For relapsed disease, advances have been made in the therapeutic arsenal for PTCL. New drugs investigated in phase II studies have achieved response rates between 10% and 30%. However, to date the identification of new therapies has been largely empiric, and long-term remissions are the exception to the rule. Current patient outcomes suggest the need for the identification and development of active and biologically rational therapies to improve disease management and to extend the duration of response with iterative biomarker evaluation. This review covers the management of PTCL and focuses on new agents and therapeutic combinations, based on a better understanding of biology and pathogenesis of the disease.Implications for practiceRecent progress in understanding of the biology and pathogenesis of peripheral T-cell lymphoma has led to the emergence of new drugs. Unfortunately, this has not been met with similar advances in outcome improvement. Anthracycline-containing regimens, mostly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), are considered the standard of care, although the best first-line approach remains to be defined. In the relapsed and refractory settings, several new agents achieved response rates between 10% and 30%, although these drugs do not significantly affect survival rates. Therapeutic options based on better molecular characterization of various histological types and combinations with the CHOP regimen or synergic combinations of new drugs may lead to better outcomes.
| S-EPMC6192612 | biostudies-literature
Project description: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).
| S-EPMC7648940 | biostudies-literature
Project description:Burkitt lymphoma (BL) is a very aggressive subtype of non-Hodgkin's lymphoma that occurs with higher frequency in patients with HIV/AIDS. Patients with HIV-related BL (HIV-BL) are usually treated with high-intensity, multi-agent chemotherapy regimens. The addition of the monoclonal antibody Rituximab to chemotherapy has also been studied in this setting. The potential risks and benefits of commonly used regimens are reviewed herein, along with a discussion of controversial issues in the practical management of HIV-BL, including concurrent anti-retroviral therapy, treatment of relapsed and/or refractory disease, and the role of stem cell transplantation.
| S-EPMC3337598 | biostudies-other
Project description:Peripheral artery disease (PAD) is a common condition with increasing prevalence domestically and worldwide. Patients with PAD have a poor prognosis, as PAD is associated with high rates of myocardial infarction, ischemic stroke, and cardiovascular disease death. The primary symptom of PAD, claudication, significantly reduces quality of life and functional status and is associated with depression. In addition to several advances in medications for PAD over the last decade, endovascular device therapy has seen a significant breakthrough in the form of paclitaxel-coated devices (PCDs), which significantly reduce rates of restenosis relative to non-PCDs, a finding which has been demonstrated in numerous randomized clinical trials. After their introduction to the market in 2012 (paclitaxel-eluting stents) and 2014 (paclitaxel-coated balloons) their use surged as they replaced non-PCDs and were designated the first-line endovascular therapy by society guidelines. This trend was abruptly reversed, however, after a meta-analysis of summary-level data was published in December of 2018 that reported an elevated mortality associated with PCDs compared with non-PCDs 2-5 years after treatment. This meta-analysis has been criticized for considerable methodological flaws. The Food and Drug Administration conducted a review and concluded that insufficient data existed to make a definitive statement regarding the safety of PCDs. They called for restriction of the use of PCDs to the highest-risk patient populations. At the same time, the FDA deemed pursuing new RCTs to better evaluate PCDs unfeasible due to the high numbers of patients and long follow-up time that would be required. In this setting, real-world data emerged as a powerful source of information for the evaluation of PCDs. Real-world data offers advantages over randomized-controlled trials including expeditious access to and analysis of data and the availability of large numbers of patients. Several retrospective observational studies demonstrate no difference in long-term all-cause mortality in patients treated with PCDs relative to those treated with non-PCDs. This paclitaxel controversy has illustrated the critical role that real-world data is assuming in long-term safety monitoring of medical devices.
| S-EPMC8169531 | biostudies-literature
Project description:Peripheral T-cell lymphomas (PTCLs) are a heterogeneous group of aggressive non-Hodgkin lymphomas. Angioimmunoblastic T-cell lymphoma (AITL) is a common subtype of PTCL, and patients with AITL typically have a poor prognosis with limited treatment options. Clinical studies have demonstrated the activity of romidepsin, a structurally unique, potent, bicyclic class 1 selective histone deacetylase inhibitor, in patients with relapsed or refractory AITL. In the case presented herein, we describe a patient treated with single-agent romidepsin at first diagnosis of AITL, resulting in complete remission for over 2 years and leading to the use of maintenance dosing. The patient eventually underwent a successful autologous stem cell transplant. This case illustrates the successful use of romidepsin for the long-term treatment of a patient with AITL in a clinical setting. Maintenance dosing may be an option for patients who have an extended response to romidepsin in order to optimize outcomes and to prolong time to the next subsequent line of therapy. In our case, the patient was able to remain in complete remission for more than 1 year while receiving maintenance dosing of romidepsin.
| S-EPMC5014944 | biostudies-literature
Project description:Commonly designated as an indolent non-Hodgkin lymphoma, follicular lymphoma (FL) presents with striking pathobiological and clinical heterogeneity. Initial management strategies for FL have evolved to involve combination chemoimmunotherapy and/or radio-immunoconjugates. Unfortunately even with the best available nontransplant treatment, which nowadays results in higher frequency of response, FL remains incurable. Although considered a feasible therapeutic option, the use of hematopoietic cell transplantation (HCT) remains controversial. The appropriate timing, graft source, and intensity of HCT conditioning regimens in FL are often matters of debate. Herein we review the available published data pertaining to the use of autologous or allogeneic HCT in patients with FL across different stages of the disease, discuss major recent advances in the field, and highlight avenues for future research. The current literature does not support a role of HCT for FL in first remission, but in the relapsed setting autologous HCT remains appropriate for patients with early chemosensitive relapses, while allogeneic transplantation remains the sole curative modality for this disease, in relatively younger patients without significant comorbidities.
| S-EPMC3477524 | biostudies-literature
Project description:Peripheral T-cell lymphomas (PTCL) represent a heterogeneous group of rare malignancies that with the exception of anaplastic lymphoma kinase expressing anaplastic large cell lymphoma, share a poor outcome after standard (eg, anthracycline-based) chemotherapy. Most patients are either refractory to initial therapy or eventually relapse. Randomized studies for relapsed/refractory PTCL are not available, however, recently published data show that conventional chemotherapy has very limited efficacy in the salvage setting. Thus, novel drugs are urgently needed to improve the outcome in this setting. Belinostat, a pan-histone deacetylase inhibitor, has demonstrated meaningful efficacy and a favorable toxicity profile in two single-arm Phase II trials on 153 patients with relapsed/refractory PTCL. The conclusive results led to an accelerated approval by the US Food and Drug Administration. The present review summarizes the clinical data available for belinostat, its current role, and future perspectives.
| S-EPMC4461120 | biostudies-literature
Project description:Single agents have demonstrated activity in relapsed and refractory (R/R) peripheral T-cell lymphoma (PTCL). Their benefit relative to combination chemotherapy remains undefined. Patients with histologically confirmed PTCL were enrolled in the Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) registry. Eligibility criteria included those with R/R disease who had received one prior systemic therapy and were given either a single agent or combination chemotherapy as first retreatment. Treatment results for those with R/R disease who received single agents were compared to those who received combination chemotherapy. The primary endpoint was best response to retreatment. Fifty-seven patients met eligibility criteria. At first retreatment, 46% (26/57) received combination therapy and 54.5% (31/57) received single agents. At median follow up of 2 years, a trend was seen towards increased complete response rate for single agents versus combination therapy (41% vs 19%; P = .02). There was also increased median overall survival (38.9 vs 17.1 months; P = .02) and progression-free survival (11.2 vs 6.7 months; P = .02). More patients receiving single agents received hematopoietic stem-cell transplantation (25.8% vs 7.7%, P = .07). Adverse events of grade 3 or 4 occurred more frequently in those receiving combination therapy, although this was not statistically significant. The data confirm the unmet need for better treatment in R/R PTCL. Despite a small sample, the analysis shows greater response and survival in those treated with single agents as first retreatment in R/R setting, while maintaining the ability to achieve transplantation. Large, randomized trials are needed to identify the best strategy.
| S-EPMC7928240 | biostudies-literature