Han Jessy Xinyi, Koh Min Jung, Boussi Leora, Sorial Mark, McCabe Sean M, Peng Luke, Singh Shambhavi, Eche-Ugwu Ijeoma Julie, Gabler Judith, Fernandez Turizo Maria J, MacVicar Caroline T, Garg Aditya, Disciullo Alexander, Chopra Kusha, Lenart Alexandra, Nwodo Emmanuel, Barnes Jeffrey, Koh Min Ji, Miranda Eliana, Chiattone Carlos, Stuver Robert, Horwitz Steven M, Merrill Mwanasha, Jacobsen Eric, Manni Martina, Civallero Monica, Skrypets Tetiana, Lymboussaki Athina, Federico Massimo, Kim Yuri, Kim Jin Seok, Cho Jae Yong, Eipe Thomas, Shet Tanuja, Sridhar Epari, Shetty Alok, Saha Saswata, Jain Hasmukh, Sengar Manju, Van Der Weyden Carrie, Prince Henry Miles, Hamouche Ramzi, Murdashvili Tinatin, Foss Francine, Gentilini Marianna, Casadei Beatrice, Zinzani Pier Luigi, Okatani Takeshi, Yoshida Noriaki, Yoon Sang Eun, Kim Won-Seog, Panchoo Girisha, Mohamed Zainab, Verburgh Estelle, Alturas Jackielyn Cuenca, Al-Mansour Mubarak, Ford Josie, Cabrera Maria Elena, Ku Amy, Bhagat Govind, Ma Helen, Sawas Ahmed, Kariya Khyati Maulik, Iwasaki Makoto, Bhanushali Forum, O'Connor Owen A, Marchi Enrica, Shen Changyu, Shah Devavrat, Jain Salvia
Massachusetts Institute of Technology, Cambridge, MA.
Georgetown University School of Medicine, Washington, DC.
Blood Adv. 2025 Feb 11;9(3):583-602. doi: 10.1182/bloodadvances.2024014674.
Variances in global access to drugs and treatment practices make it challenging to understand the benefit of contemporary therapies in patients with relapsed and refractory (R/R) mature T-cell and natural killer-cell lymphomas (MTCL and MNKCL). We conducted an international retrospective cohort study of 925 patients with R/R MTCL and MNKCL. In peripheral T-cell lymphoma-not otherwise specified and anaplastic lymphoma kinase-negative anaplastic large cell lymphoma (ALK- ALCL), patients with relapsed lymphoma demonstrated a superior median overall survival (OS) relative to refractory from the time of second-line treatment. We identified several independent predictors of OS for R/R lymphoma including age >60 years, primary refractory disease, histological subtype other than angioimmunoblastic T-cell lymphoma (AITL), extranodal sites >1, Ki67 ≥40%, and absolute lymphocyte count less than the lower limit of normal. A multivariable model incorporating these formed the basis for a prognostic index for R/R TCL, in which patients are stratified into low-risk (0-1 risk factor), intermediate-risk (2-3 risk factors), or high-risk (≥4 risk factors) groups, which were associated with 3-year OS of 57.14%, 23.3%, and 7%, respectively. Patients received either a "novel" single agent (SA; 35%) or cytotoxic chemotherapy (CC; 60%) for their second-line treatment. Higher progression-free survival was observed with SA over CC for the entire cohort with a higher 3-year OS in AITL and ALK- ALCL. Among the SA, small-molecule inhibitors demonstrated OS advantage relative to CC in AITL. Our results highlight continued efficacy of novel drugs globally and the potential of a new prediction model in informing heterogeneous prognosis within the R/R population of MTCL and MNKCL.
全球药物可及性和治疗方法的差异使得了解当代疗法对复发难治性（R/R）成熟T细胞和自然杀伤细胞淋巴瘤（MTCL和MNKCL）患者的益处具有挑战性。我们对925例R/R MTCL和MNKCL患者进行了一项国际回顾性队列研究。在未另行指定的外周T细胞淋巴瘤和间变性淋巴瘤激酶阴性间变性大细胞淋巴瘤（ALK- ALCL）中，复发淋巴瘤患者从二线治疗时起的中位总生存期（OS）优于难治性患者。我们确定了R/R淋巴瘤OS的几个独立预测因素，包括年龄>60岁、原发性难治性疾病、血管免疫母细胞性T细胞淋巴瘤（AITL）以外的组织学亚型、结外部位>1个、Ki67≥40%以及绝对淋巴细胞计数低于正常下限。纳入这些因素的多变量模型构成了R/R TCL预后指数的基础，其中患者被分为低风险（0-1个风险因素）、中风险（2-3个风险因素）或高风险（≥4个风险因素）组，其3年OS分别为57.14%、23.3%和7%。患者二线治疗接受“新型”单药（SA；35%）或细胞毒性化疗（CC；60%）。整个队列中，SA组的无进展生存期高于CC组，AITL和ALK- ALCL的3年OS更高。在SA中，小分子抑制剂在AITL中相对于CC显示出OS优势。我们的结果突出了全球新型药物的持续疗效以及新预测模型在MTCL和MNKCL的R/R人群中告知异质性预后的潜力。
