Department of Hematology, Centre Hospitalier Le Mans, Le Mans, France
Department of Hematology, Centre Hospitalier Le Mans, Le Mans, France.
Oncologist. 2018 Sep;23(9):1039-1053. doi: 10.1634/theoncologist.2017-0524. Epub 2018 Apr 19.
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.
Recent 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.
外周 T 细胞淋巴瘤 (PTCL) 是一组临床侵袭性疾病，具有不良预后。尽管近年来取得了进展，通过分子谱分析和下一代测序加深了对 PTCL 的自然史和生物学的理解，但仍需要改进新诊断患者的化疗方案疗效。一线治疗通常是环磷酰胺、多柔比星、长春新碱和泼尼松 (CHOP) 或 CHOP 样方案，但这些方案的失败率高，复发频繁。评估强化化疗的试验在延长无事件生存方面取得了不同程度的成功，但总体生存率保持不变。此外，这种策略仅限于初始蒽环类化疗后完全缓解的患者。许多患者因年龄或未达到缓解而不适合造血干细胞移植。对于复发疾病，PTCL 的治疗武器库取得了进展。在 II 期研究中研究的新药已达到 10%至 30%的缓解率。然而，迄今为止，新疗法的确定在很大程度上是经验性的，长期缓解是例外情况。目前患者的结果表明需要确定和开发有效的、基于生物学的治疗方法，以改善疾病管理并通过迭代生物标志物评估延长缓解期。这篇综述涵盖了外周 T 细胞淋巴瘤的管理，重点介绍了基于对疾病生物学和发病机制的更好理解的新药物和治疗组合。
对外周 T 细胞淋巴瘤生物学和发病机制的理解的最新进展导致了新药物的出现。不幸的是，这并没有带来类似的改善结果的进展。含蒽环类药物的方案，主要是环磷酰胺、多柔比星、长春新碱和泼尼松 (CHOP)，被认为是标准治疗方法，尽管最佳的一线治疗方法仍有待确定。在复发和难治性环境中，几种新药物达到了 10%至 30%的缓解率，尽管这些药物对生存率没有显著影响。基于对各种组织学类型的更好分子特征的治疗选择以及与 CHOP 方案的组合或新药物的协同组合可能会带来更好的结果。
