Treatments and Outcomes of Patients With Extranodal Natural Killer/T-Cell Lymphoma Diagnosed Between 2000 and 2013: A Cooperative Study in Japan

2017 ◽  
Vol 35 (1) ◽  
pp. 32-39 ◽  
Author(s):  
Motoko Yamaguchi ◽  
Ritsuro Suzuki ◽  
Masahiko Oguchi ◽  
Naoko Asano ◽  
Jun Amaki ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Free Survival ◽  
Natural Killer T Cell ◽  
Soluble Interleukin 2 Receptor ◽  
Killer T Cell

Purpose To elucidate the management and outcomes of patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKL), who were diagnosed between 2000 and 2013 in Japan. Patients and Methods Data from 358 patients with ENKL diagnosed between 2000 and 2013 from 31 institutes were retrospectively analyzed. Results Patients’ median age was 58 years, and 257 (72%) had localized disease. The most common first-line treatment was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%) for localized ENKL and L-asparaginase–containing chemotherapy (30%) for advanced ENKL. With a median follow-up of 5.8 years, overall survival (OS) rates at 5 years for localized and advanced ENKL were 68% and 24%, respectively. The prognostic index of natural killer lymphoma was validated in our study, although only 4% of patients with localized ENKL were classified as high risk. With a median follow-up of 5.6 years, OS and progression-free survival at 5 years in the 150 patients who received RT-DeVIC in clinical practice were 72% (95% CI, 63% to 78%) and 61% (95% CI, 52% to 69%), respectively. Toxicities of RT-DeVIC were comparable to those in a previous trial. Multivariate analysis in patients with localized ENKL who received RT-DeVIC identified elevated soluble interleukin-2 receptor as an independent predictive factor for worse OS and progression-free survival (adjusted hazard ratios, 2.28 and 2.46; 95% CI, 1.24 to 4.23 and 1.42 to 4.28; P = .008 and .0014, respectively). Conclusion Favorable OS in response to new treatments was demonstrated in a large number of patients. Improved treatment approaches are needed for localized ENKL exhibiting elevated pretreatment soluble interleukin-2 receptor.

Concurrent Radiotherapy and Dexamethasone, Etoposide, Ifosfamide, and Carboplatin (DeVIC) for Patients with Localized Extranodal Natural Killer/T-Cell Lymphoma, Nasal Type: A Single Institution Analysis in Japan

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1611-1611
Author(s):  
Eriko Nara ◽  
Masahiro Yokoyama ◽  
Kengo Takeuchi ◽  
Kenji Nakano ◽  
Kyoko Ueda ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Concurrent Chemoradiotherapy ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Free Survival ◽  
Nasal Type ◽  
Natural Killer T Cell ◽  
Concurrent Radiotherapy ◽  
Killer T Cell

Abstract Abstract 1611 Background: Extranodal natural killer/T-cell lymphoma (ENKL), nasal type, is a recognized a rare distinct entity strongly associated EBV infection, accounting for 3% to 10% of malignant lymphomas in East Asia. Recent studies suggest that concurrent chemoradiotherapy was effective as first-line therapy for patients with localized ENKL, nasal type. We assess treatment results with concurrent chemoradiotherapy for ENKLs. Patients and methods: From December 2007 to July 2010, newly diagnosed localized ENKL, nasal type, and treated with concurrent radiotherapy (median 50 Gy; range 46–56 Gy) and 3 cycles of dexamethasone, etoposide, ifosfamide, and carboplatin (DeVIC) at the Cancer Institute Hospital, Tokyo, Japan were analyzed retrospectively. All the histopathological samples were reviewed according to the WHO classification by expert hematopathologists. Results: Total of sixteen patients was identified. Baseline patients. characteristics included a median age of 56.5 years (range; 30–76 years), eleven men and five women, thirteen patients (81%) with stage IE and three (19%) with stage IIE. For IPI, patients with low and low-intermediate risks were thirteen patients (81%) and three (19%), respectively. For NKIPI, patients with group 1, 2, and 3 were six patients (37%), seven (44%), and three (19%), respectively. All patients received concurrent chemoradiotherapy, and eleven patients (69%) achieved complete remission, with 2 partial remissions. The overall response rate was 81%. At a median follow-up of 17 months (range; 2–44), the 2-year progression-free survival and overall survival rates were 54.7% and 61.1%, respectively. Seven patients were confirmed progression disease, and six died from progression of lymphoma. Grade 3/4 adverse events were leukopenia (100%), neutropenia (100%), anemia (19%), mucositis (63%), anorexia (81%), and febrile neutropenia (25%), respectively. Seven patients were confirmed progression disease, and six died from progression of lymphoma. No treatment-related deaths were observed. Conclusions: Concurrent radiotherapy and DeVIC for patients with localized ENKL, nasal type, demonstrated favorable outcomes. We are now investigating what factors indicate good or poor prognosis in this regimen. Progression free survival of concurrent radiotherapy and DeVIC regimen Disclosures: Yokoyama: CHUGAI PHARMACEUTICAL CO.,LTD: Consultancy. Mishima:CHUGAI PHARMACEUTICAL CO.,LTD: Consultancy.

Efficacy and Safety Of Pegaspargase With Gemcitabine and Oxaliplatin In Patients With Treatment-naïve, Refractory Extranodal Natural Killer/T-Cell Lymphoma: A Single-Centre Experience

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 642-642 ◽  
Author(s):  
Yan Gao ◽  
Hui-qiang Huang ◽  
Cai QiChun ◽  
XiaoXiao Wang ◽  
QinfQing Cai ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Natural Killer T Cell ◽  
Treatment Naïve ◽  
Killer T Cell

Abstract Purpose Extranodal natural killer/T-cell lymphoma (ENKTL) is an aggressive lymphoma with poor prognosis. The response rate to L-asperagenase(L-ASP) based multi-agent regimens is highly effective. Several clinical trials demonstraed good response and less toxicity for pegaspargase (PEG-ASP) in comparison to L-ASP. This is the first prospective study to evaluate the efficacy and safety of PEG-ASP combined with gemcitabine and oxaliplatin (PEG-ASP + Gemox) for patients with treatment-naïve and refractory or relapsed ENKTL. Patients and methods 61 eligible patients treated by PEG-ASP + Gemox from March 2010 to March 2013 were analyzed. 36 newly -diagnosed patients and 25 refracrory/replased patients were enrolled, we also conducted extra matched-pair analysis between 20 stage IE/IIE cases selected from 36 newly -diagnosed patients in PEG-ASP + Gemox group and 18 stage IE/IIE patients in L-ASP + Gemox regimen group(unpublished data, Table 1,2). PEG-ASP + Gemox dosages were as follows: Gemcitabine 1000 mg/m2; day 1,8; oxaliplatin 130 mg/m2 day 1, PEG-ASP 2500 U/m2 im day1. The regimen was repeated every 3 weeks for a maximum of 6 cycles including 3 cycles induction chemotherapy for stage IE/IIE patients followed by involved-field radiotherapy. Furthermore autologous haematopoietic stem cell transplantation(AHSCT) was recommended to refractory/relapsed patients after achieved good response. Results 55 patients were evaluable for response after a median 4 (1¨C6 ) cycles. The overall response(OR) rate was 90.9% (50/55), with a complete remission (CR) rate of 60.0% (33/55). After a median follow-up of 16.2 (4.0-39.5)months, the 1-, 2-year OS rates were 88.2%, 83.2%, and the 1-, 2- year PFS rates were all 85.2%. The median follow-up time was 19.6 (4.0-39.5)months for treatmen-naive patients. their OR, CR, partial remission(PR) rates were 94.0% (31/33), 66.7% (22/33), 27.3% (9/33), respectively. Both 1-, 2-year OS rates were 94.0%, 1-, 2-year PFS rates were all 93.9%. The median follow-up time was 18.7(4.5-36.2) months for refractory/replased patients. The OR and CR rates were 86.4% (19/22), 50.0% (11/22). The 1-, 2-year OS rates were 80.4% ,70.4%, the 1-, 2-year PFS rates were all 72.7%. Patients who achieved CR had undergone a median of two cycles (2¨C6). All patients received 187 cycles of chemotherapy, the incidence of rates of grade 1 and 2 adverse events were as follows: neutropenia, 69.6%; vomit 39.5%, transaminase elevation, 37.9%. Grade 3 and 4 adverse reactions were rare. Conclusion Our clinical trisl have demonstrated high efficacy and quick achievement of CR for the first time for PEG-ASP+Gemox regimen in the management of treatment-naïve and refractory/relapsed ENKTL patients. It also provided good chance of AHSCT as consolidation for chemosensitive patients. Meanwhile, PEG-ASP+Gemox regimen was conveniant and less toxic. Further investigation for PEG-ASP + Gemox regimen is warranted. Disclosures: No relevant conflicts of interest to declare.

scholarly journals A Phase II Study of Bortezomib-GIFOX (Gemcitabine, Ifosfamide, Oxaliplatin) in Patients with Newly Diagnosed Natural-Killer/T-Cell Lymphoma

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5353-5353 ◽  
Author(s):  
Tiffany Tang ◽  
Kevin Tay ◽  
Miriam Tao ◽  
Richard Hong Hui Quek ◽  
Mohamad Farid ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Phase Ii ◽  
Phase Ii Study ◽  
Cell Lymphoma ◽  
Stage Ii ◽  
Newly Diagnosed ◽  
Natural Killer T Cell ◽  
Killer T Cell

Abstract Background: Natural-killer/T-cell lymphoma (NKTL) is a subtype of non-Hodgkin's lymphoma with poor response to conventional chemotherapy. Gene expression profiling of NKTL revealed overexpression of NF-kB. Bortezomib (B) is a potent and reversible proteasome inhibitor which has shown single agent activity in preclinical models of NKTL in vitro and in vivo. Further, drug testing in mouse NKTL xenograft suggest gemcitabine (G), oxaliplatin (ox) and ifosfamide (if) were effective in inducing tumor regression. We have also previously published a patient with relapsed NKTL that was successfully treated with GIFOX therapy. Hence we conducted a study to evaluate the clinical efficacy of B-GIFOX in patients with newly diagnosed NKTL. Methods: This was an open-labelled prospective phase II study approved by the institutional review board. Patients with histologically confirmed NKTL with stage IB or bulky(X) and stage II-IV disease were included. Patients with stage IB/IX or II were treated with 4 cycles of B-GIFOX followed by radiotherapy. Patients with advanced stage disease were treated with 6 cycles of B-GIFOX. Intravenous B was dosed at 1.3mg/m2 on days 1, 4, 8, and 11 every 21 days. Dose and schedule of G, If and Ox were 1000mg/m2 on day 1, 5g/m2 on day 2 and 85mg/m2 on day 2 respectively. The primary objective was to estimate the overall response rates (ORR) and the secondary objectives were to estimate the progression free survival (PFS), overall survival (OS) and toxicities of this regimen. PFS was calculated from the start of treatment to the date of progression or last follow-up. OS was calculated from the start of treatment to the date of death or last follow-up. Both median PFS and OS were estimated using Kaplan-meier curves. Results: There were 7 patients recruited into the study; 3 had stage II disease and 4 had stage IV disease. The median age was 50 years (range: 34-61) and 5 (71.4%) were male. Four patients had B symptoms and all but one patient had elevated LDH at diagnosis. Six patients completed their planned treatment and one patient had disease progression through the first cycle of chemotherapy. The ORR was 42.8%; one patient had a complete response, two had partial responses and 4 had progressive disease. The median PFS was 4.3months (95% confidence interval [CI] 4.0-4.6 months) and the median OS was 14.9months (95% CI 0.6-29.2 months). The following grade 1-2 toxicities were seen in at least 1 patient: anemia (7), thrombocytopenia (5), fever (3), ALT increase (3), nausea (2), vomiting (2), ALP increase (2), AST increase (1), alopecia (1), fatigue (1), and body ache (1). The following grade 3-4 toxicities were seen in at least 1 patient: thrombocytopenia (2), and tumor lysis syndrome (1). Conclusion: This study showed that B-GIFOX induced an ORR of 43% in patients with newly diagnosed NKTL however the median PFS was short at around 4months. Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Characteristics and Survival of Non-Nasal Natural Killer/T-Cell Lymphoma from 2 Cancer Centers from Peru

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4535-4535
Author(s):  
Jule F Vasquez ◽  
Melanie Castro ◽  
Alonso Diaz ◽  
Carlos Barrionuevo ◽  
Cesar Samanez-Figari
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
T Cell ◽  
Natural Killer ◽  
Clinical Characteristics ◽  
Median Overall Survival ◽  
Cell Lymphoma ◽  
Natural Killer T Cell ◽  
Killer T Cell

Abstract Background Natural killer/T-cell lymphoma (NKTCL) is an aggressive lymphoma with poor prognosis mainly seen in Asian and South American countries, most patients have nasal involvement. Non-nasal NKTCL have a dismal prognosis. However, data about this very specific population is mostly known in Asians but little known in Latin American (LATAM) population. Our aim is to describe the clinical characteristics and survival of newly diagnosed NKTCL patients in Peru Methods: This is a retrospective study, including all patients with a pathological diagnosis of NKTCL patients >13 years at the Instituto Nacional de Enfermedades Neoplasicas (INEN) and Oncosalud between 2002 and 2019. The estimate of the survival curves was performed by the Kaplan-Meier method, and the difference was computed by the log-rank test. Results: 60 patients were included for the analysis. The median age was 37 years (range 15-83). 62% were male, 51% had B-symptoms, 56% had stage III/IV disease, 54% had elevated serum LDH, 29% had nodal involvement. The most frequent non-nasal sites were oropharynx, soft tissue, cutaneous, gastrointestinal and orbit with 24%, 17%, 12%, 7% and 5%, respectively. 79% patients received systemic chemotherapy, 7% received radiotherapy alone and 14% did not received chemotherapy because poor performance status. Of patients who received chemotherapy only 20% received a L-asparaginase-based chemotherapy. The median follow-up time was 8 months (1-103). The median overall survival (OS) was 14 months (interquartile range [IQR] 4-29), 1y OS was 51% (95% CI 33-67), 3y OS 21% (95% CI 7-40), 5y OS 14% (95% CI 3-34), figure 1. The median overall survival according to LDH level was 10 months regardless of the levels (p=0.84), figure 2. The median OS for female and male were 8 and 10 months, respectively p=0.59) Conclusions: Peruvian patients with non-nasal NKTCL are younger, with presence of B-symptoms, advance stage and elevated LDH levels compared to those reported in nasal NKTCL. The most frequent non nasal NKTCL is located on the oropharynx. OS of non-nasal NKTCL is extremely poor. Elevated LDH and sex are not prognostic factors for OS. A larger cohort and follow-up are needed to evaluate prognostic factors in this population. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals Consolidative Treatment after Salvage Chemotherapy Improved Prognosis in Patients with Relapsed Extranodal Natural Killer/T-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5086-5086
Author(s):  
Xi-Wen Bi ◽  
Wen-Wen Zhang ◽  
Jia-Jia Huang ◽  
Zhongjun Xia ◽  
Zhi-Ming Li ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
Salvage Chemotherapy ◽  
Salvage Treatment ◽  
First Line ◽  
Natural Killer T Cell ◽  
Locoregional Relapse ◽  
Killer T Cell

Abstract The optimal treatment strategy and prognosis for patients with relapsed natural killer/T-cell lymphoma (NKTCL) remain largely unknown. The treatment modalities and prognosis of fifty-six patients with relapsed NKTCL were retrospectively reviewed. Twenty-three (41.1%) patients had locoregional relapse alone, while 33 (58.9%) had distant with or without locoregional relapse. Chemotherapy was the initial salvage treatment, followed by radiotherapy (RT) or autologous hematopoietic stem cell transplantation (AHSCT) as consolidative therapy, depending on the status of remission and the pattern of relapse. The 5-year overall survival (OS) after relapse was 41.4% for the entire cohort. Complete remission (CR) after salvage treatment was associated with a substantially better survival (5-year OS after relapse: 74.7 vs. 7.8%, P < 0.001). For patients with locoregional relapse alone, consolidative RT after response to salvage chemotherapy significantly improved prognosis compared with follow-up (5-year OS: 83.3 vs. 41.7%, P = 0.047). For patients with distant relapse, the addition of consolidative AHSCT after response to chemotherapy significantly prolonged survival than follow-up (2-year OS: 100.0 vs. 20.0%, P = 0.004). Patients without consolidative treatment after response to salvage chemotherapy had a comparable survival to those who experienced stable or progressive disease after chemotherapy, regardless of the relapse pattern. Asparaginase (ASP)-containing salvage chemotherapy failed to convey a survival advantage over ASP-absent chemotherapy (5-year OS: 44.2 vs. 39.3%, P = 0.369). Patients who received ASP-containing chemotherapy in the first-line treatment had a poorer response to salvage chemotherapy and worse prognosis after relapse, compared with those receiving ASP-absent first-line chemotherapy. Consolidative RT or AHSCT improved prognosis in patients with relapsed NKTCL who responded to initial salvage chemotherapy. The role of ASP in salvage chemotherapy after relapse required further exploration in prospective studies. Disclosures No relevant conflicts of interest to declare.

Phase II clinical trial of first-line combination of radiation followed by gemcitabine, dexamethasone, and cisplatin (GDP) chemotherapy for early-stage extranodal natural killer/T-cell lymphoma with unfavorable prognostic factors: The GREEN study (NCT02276248).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7540-7540
Author(s):  
Fei Qi ◽  
Wei-Hu Wang ◽  
Ye-Xiong Li ◽  
Mei Dong ◽  
Xiao-hui He ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Prognostic Factors ◽  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
Early Stage ◽  
First Line ◽  
Natural Killer T Cell ◽  
Killer T Cell

7540 Background: Currently concomitant or sequential chemotherapy with radiotherapy has been recognized as the standard treatment for extranodal natural killer/T-cell lymphoma, nasal type (ENKTL). However, the optimal schedule has not been fully defined. Methods: We designed a phase II prospective study to investigate the efficacy and toxicity profile of sequential radiation followed by systemic GDP (gemcitabine, dexamethasone and cisplatin) chemotherapy on previously untreated early-staged (stage IE/IIE) ENKTL patients with at least one unfavorable prognostic factor. The primary endpoint was 2-year progression-free survival (PFS). Secondary endpoints were 2-year overall survival (OS), overall response rate (ORR), and toxicity. Results: A total of40 patients were enrolled and completed the entire course of treatment between June 2010 and June 2014. The median age was 38 (range 25-63) years old. All the enrolled patients presented with at least one unfavorable prognostic feature: age > 60 years (5.0%), B symptom (40%), elevated serum LDH (40.0%), regional lymph node involvement (32.5%) and primary tumor invasion (87.5%). At the completion of the whole treatment, ORR was 97.5% and the complete remission rate was 95.0%. Median follow-up time was 43.7 months (range 9.4-72.3 months). 2-, 3-, 5-year PFS rates were 84.7%, 82.1%, 77.5%, and OS rates were 89.9%, 87.1%, 79.7%, respectively. Recurrence within the RT field was observed in four patients and systemic failure in three individuals. Grade 1-2 skin reaction and mucositis were the main toxicity related to radiation. Grade 3-4 neutropenia (12/40), thrombocytopenia (7/40) and anemia (2/40) were observed during GDP chemotherapy. No clinically significant late toxicities were observed during follow-up visits. Conclusions: The current results indicates that first-line radiation followed by GDP chemotherapy can be one of the most effective and feasible treatment schedule for early-stage ENKTL patients, especially those with poor prognostic factors. Clinical trial information: NCT02276248.

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