Survival outcomes of patients with extranodal natural-killer T-cell lymphoma: a prospective cohort study from the international T-cell Project

Fox, Christopher P.; Civallero, Monica; Ko, Young Hyeh; Manni, Martina; Skrypets, Tetiana; Pileri, Stefano; Kim, Seok Jin; Cabrera, María Elena; Shustov, Andrei R.; Chiattone, Carlos S.; Horwitz, Steven M.; Dlouhy, Iván; Spina, Michele; Hitz, Felicitas; Montoto, Silvia; Nagler, Arnon; Martínez, Virginia; Souza, Cármino Antônio de; Fernández-Álvarez, Rubén; Ballova, Veronika; Gabús, Raúl; Inghirami, Giorgio; Federico, Massimo; Kim, Won Seog

doi:10.1016/s2352-3026(19)30283-2

Cited by 95 publications

(126 citation statements)

References 24 publications

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“…Patients who had received non-ANT-based regimen CT alone were also excluded, as CT alone is no longer considered a standard treatment option for early-stage ENKTCL because of its poor outcome. 24,25,31 Eventually, 1360 patients with early-stage disease formed the study population. Our institutional review board approved this project.…”

Section: Eligibility and Study Populationmentioning

confidence: 99%

Risk‐based, response‐adapted therapy for early‐stage extranodal nasal‐type NK/T‐cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study

Yang

Zhang

et al. 2020

American J Hematol

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We aimed to determine the survival benefits of chemotherapy (CT) added to radiotherapy (RT) in different risk groups of patients with early‐stage extranodal nasal‐type NK/T‐cell lymphoma (ENKTCL), and to investigate the risk of postponing RT based on induction CT responses. A total of 1360 patients who received RT with or without new‐regimen CT from 20 institutions were retrospectively reviewed. The patients had received RT alone, RT followed by CT (RT + CT), or CT followed by RT (CT + RT). The patients were stratified into different risk groups using the nomogram‐revised risk index (NRI). A comparative study was performed using propensity score‐matched (PSM) analysis. Adding new‐regimen CT to RT (vs RT alone) significantly improved overall survival (OS, 73.2% vs 60.9%, P < .001) and progression‐free survival (PFS, 63.5% vs 54.2%, P < .001) for intermediate‐risk/high‐risk patients, but not for low‐risk patients. For intermediate‐risk/high‐risk patients, RT + CT and CT + RT resulted in non‐significantly different OS (77.7% vs 72.4%; P = .290) and PFS (67.1% vs 63.1%; P = .592). For patients with complete response (CR) after induction CT, initiation of RT within or beyond three cycles of CT resulted in similar OS (78.2% vs 81.7%, P = .915) and PFS (68.2% vs 69.9%, P = .519). For patients without CR, early RT resulted in better PFS (63.4% vs 47.6%, P = .019) than late RT. Risk‐based, response‐adapted therapy involving early RT combined with CT is a viable, effective strategy for intermediate‐risk/high‐risk early‐stage patients with ENKTCL in the modern treatment era.

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Section: Eligibility and Study Populationmentioning

confidence: 99%

Risk‐based, response‐adapted therapy for early‐stage extranodal nasal‐type NK/T‐cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study

Yang

Zhang

et al. 2020

American J Hematol

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“…Over the past decade, substantial treatment advances have been made with the introduction of novel prognostic models and risk stratifications [8][9][10], upfront radiotherapy [11][12][13][14], and non-anthracycline (ANT)-based chemotherapy [15][16][17][18][19][20][21]. The treatment outcome has improved, with 5-year overall survival (OS) rates of 60-90% reported for localized diseases, but only 10-40% for disseminated diseases [10,13,[22][23][24][25]. A large proportion of patients suffers disease progression or relapse after employment of the current standard treatment.…”

Section: Introductionmentioning

confidence: 99%

Progression-free survival at 24 months and subsequent survival of patients with extranodal NK/T-cell lymphoma: a China Lymphoma Collaborative Group (CLCG) study

et al. 2020

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Limited evidence supports the use of early endpoints to evaluate the success of initial treatment of extranodal NK/T-cell lymphoma (ENKTCL) in the modern era. We aim to analyze progression-free survival at 24 months (PFS24) and subsequent overall survival (OS) in a large-scale multicenter cohort of patients. 1790 patients were included from the China Lymphoma Collaborative Group (CLCG) database. Subsequent OS was defined from the time of PFS24 or progression within 24 months to death. OS was compared with age- and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Patients who did not achieve PFS24 had a median OS of 5.3 months after progression, with 5-year OS rate of 19.2% and the SMR of 71.4 (95% CI, 62.9–81.1). In contrast, 74% patients achieved PFS24, and the SMR after achieving PFS24 was 1.77 (95% CI, 1.34–2.34). The observed OS rate after PFS24 versus expected OS rate at 5 years was 92.2% versus 94.3%. Similarly, superior outcomes following PFS24 were observed in early-stage patients (5-year OS rate, 92.9%). Patients achieving PFS24 had excellent outcome, whereas patients exhibiting earlier progression had a poor survival. These marked differences suggest that PFS24 may be used for study design and risk stratification in ENKTCL.

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“…[5][6][7] In contrast to localized NKTL where front-line therapy may be associated with long-term remission in over 60% of patients, the optimal treatment for advanced NKTL remains a major challenge as 70-80% of the patients experience disease progression or death within 5 years of diagnosis. [8][9][10][11] Asparaginase and pegaspargase are key components of chemotherapeutic regimens for advanced NKTL. [12][13][14] However, treatment-related adverse events (AEs) still remain a significant challenge.…”

Section: Introductionmentioning

confidence: 99%

Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma

Cai

Huang

et al. 2020

Sig Transduct Target Ther

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Advanced natural killer/T cell lymphoma (NKTL) has demonstrated poor prognosis with currently available therapies. Here, we report the efficacy of anti-programmed death 1 (PD-1) antibody with the P-GEMOX (pegaspargase, gemcitabine, and oxaliplatin) regimen in advanced NKTL. Nine patients underwent six 21-day cycles of anti-PD-1 antibody (day 1), pegaspargase 2000 U/m2 (day 1), gemcitabine 1 g/m2 (days 1 and 8) and oxaliplatin 130 mg/m2 (day 1), followed by anti-PD-1 antibody maintenance every 3 weeks. Programmed death-ligand 1 (PD-L1) expression and genetic alterations were determined in paraffin-embedded pretreatment tissue samples using immunohistochemistry and next-generation sequencing (NGS) analysis. Responses were assessed using 18F-fluorodeoxyglucose positron emission tomography (18FDG-PET) and computed tomography or magnetic resonance imaging. Eight patients exhibited significant responses, comprising of seven complete remissions and one partial remission (overall response rate: 88.9%). After a median follow-up of 10.6 months, 6/9 patients (66.7%) remained in complete remission. The most common grade 3/4 adverse events were anemia (33.3%), neutropenia (33.3%), and thrombocytopenia (33.3%); all of which were manageable and resolved. Immunochemotherapy produced a high response rate in patients with positive PD-L1 expression (5/6, 83.3%). NGS analysis suggested that STAT3/JAK3/PD-L1 alterations and ARID1A mutation were associated with immunochemotherapy efficacy. Mutation in DDX3X and alteration in epigenetic modifiers of KMT2D, TET2, and BCORL1 might indicate a poor response to immunochemotherapy. In conclusion, the anti-PD-1 antibody plus P-GEMOX regimen demonstrated promising efficacy in advanced NKTL. PD-L1 expression combined with specific genetic alterations could be used as potential biomarkers to predict therapeutic responses to immunochemotherapy.

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Survival outcomes of patients with extranodal natural-killer T-cell lymphoma: a prospective cohort study from the international T-cell Project

Cited by 95 publications

References 24 publications

Risk‐based, response‐adapted therapy for early‐stage extranodal nasal‐type NK/T‐cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study

Risk‐based, response‐adapted therapy for early‐stage extranodal nasal‐type NK/T‐cell lymphoma in the modern chemotherapy era: A China Lymphoma Collaborative Group study

Progression-free survival at 24 months and subsequent survival of patients with extranodal NK/T-cell lymphoma: a China Lymphoma Collaborative Group (CLCG) study

Combination of anti-PD-1 antibody with P-GEMOX as a potentially effective immunochemotherapy for advanced natural killer/T cell lymphoma

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