INTERNATIONAL EXTRANODAL NK/T-CELL LYMPHOMA PROJECT: PROGNOSTIC FACTORS IN THE ERA OF NONANTHRACYCLINE-BASED TREATMENT
(Abstract release date: 05/21/15)
EHA Library. Kim S. 06/12/15; 103208; S110
Disclosure(s): Samsung Medical CenterMedicine
Prof. Seok Jin Kim
Contributions
Contributions
Abstract
Abstract: S110
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 12:30 to 12.06.2015 12:45
Location: Room A7
Background
Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare type of non-Hodgkin lymphoma with poor prognosis because tumor cells are frequently resistant to anthracycline-containing chemotherapy such as CHOP due to expression of the multidrug-resistant p-glycoprotein. As a result, the treatment strategy for ENKTL has changed to non-anthracycline based regimens such as SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) with or without radiotherapy. Thus, concurrent chemoradiotherapy followed by non-anthracycline based chemotherapy is recommended for localized disease whereas intensified chemotherapy such as SMILE is for advanced disease. However, there is no proven prognostic model for ENKTL in the era of this new treatment strategy because previous prognostic models were developed by analyzing patients who were treated with CHOP or CHOP-like regimens.
Aims
This study is to explore risk factors for poor progression-free survival (PFS) and overall survival (OS) in ENKTL, and establish a prognostic model for ENKTL patients treated with non-anthracycline based treatment.
Methods
This is a retrospective cohort study using anonymized information from patients with ENKTL. The following criteria are required: (1) Patients diagnosed with ENKTL, nasal type between January 1, 1995 and December 31, 2012; (2) Patients treated with non-anthracycline based therapy as an initial treatment. The pathology of initial diagnosis was reviewed by designated pathologists.
Results
The data of 557 patients were from 32 hospitals from six Asian countries (Korea, Japan, Hong Kong China, Singapore, Taiwan, and Malaysia) and 6 hospitals from five Western countries (France, Germany, Denmark, Sweden, and USA). Thirty cases were excluded from the analysis due to following reasons: Missing follow-up data, different pathology from ENKTL, and different treatment regimens containing anthracycline. Thus, 527 patients were analyzed, and male (n = 341) was predominant compared to female (n = 186). 70% of patients were ≤ 60 years at diagnosis whereas 30% was older than 60 years. Two-thirds of patients had stage I/II (n = 346) and nasal tract was most commonly involved extranodal site (n = 421, 80%). Bone marrow involvement was observed in 83 patients (16%), and distant lymph nodes were involved in 86 patients (16%). With a median follow-up of 45 months (IQR: 22-65 months), 306 patients (58%) were alive at the time of analysis and the event of progression-free survival occurred in 272 patients including relapse or progression (n = 187). The median OS was 76 months (95% CI: 51-101 months) and PFS was 32 months (95% CI: 20-45 months). The multivariate analysis for OS and PFS showed a significant association of four parameters with survival outcomes: age > 60, stage III/IV, distant lymph node involvement, and non-nasal tract involvement (P < 0.001). Thus, the prognosis of patients with age > 60, stage III/IV and distant lymph node involvement was poor, and patients who did not involve nasal tract also showed worse OS and PFS than patient with nasal tract involvement. Thus, we gave one score for each parameter. According to the sum of scores, patients with score 0 or 1 were grouped as low risk, score 2 was intermediate, and score 3 or 4 was high risk. This new risk model showed a strong association with OS and PFS (Figure 1). Among 328 patients who were initially evaluated for EBV DNA in blood, 189 patients (58%) showed detectable level of EBV DNA. The multivariate analysis including EBV DNA titer focused on these 328 patients showed that aforementioned four parameters and the presence of EBV DNA were independently associated with OS and PFS. Thus, we proposed another risk model for patients who had EBV DNA data with these five parameters consisting of low (score 0/1), low-intermediate (score 2), high-intermediate (score 3), and high risk (score 4/5).
Summary
Our multinational, multicenter retrospective study proposed a new prognostic model for newly diagnosed ENKTL patients who were treated with non-anthracycline based treatment. It consists of age > 60, stage III/IV, distant lymph node involvement, and no involvement of nasal tract. Our finding will be validated by currently ongoing study with an independent cohort including China.
Keyword(s): Lymphoma, NK-T cells, Prognostic factor
Session topic: Treatment and outcome in non-Hodgkin lymphomas
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 12:30 to 12.06.2015 12:45
Location: Room A7
Background
Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare type of non-Hodgkin lymphoma with poor prognosis because tumor cells are frequently resistant to anthracycline-containing chemotherapy such as CHOP due to expression of the multidrug-resistant p-glycoprotein. As a result, the treatment strategy for ENKTL has changed to non-anthracycline based regimens such as SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) with or without radiotherapy. Thus, concurrent chemoradiotherapy followed by non-anthracycline based chemotherapy is recommended for localized disease whereas intensified chemotherapy such as SMILE is for advanced disease. However, there is no proven prognostic model for ENKTL in the era of this new treatment strategy because previous prognostic models were developed by analyzing patients who were treated with CHOP or CHOP-like regimens.
Aims
This study is to explore risk factors for poor progression-free survival (PFS) and overall survival (OS) in ENKTL, and establish a prognostic model for ENKTL patients treated with non-anthracycline based treatment.
Methods
This is a retrospective cohort study using anonymized information from patients with ENKTL. The following criteria are required: (1) Patients diagnosed with ENKTL, nasal type between January 1, 1995 and December 31, 2012; (2) Patients treated with non-anthracycline based therapy as an initial treatment. The pathology of initial diagnosis was reviewed by designated pathologists.
Results
The data of 557 patients were from 32 hospitals from six Asian countries (Korea, Japan, Hong Kong China, Singapore, Taiwan, and Malaysia) and 6 hospitals from five Western countries (France, Germany, Denmark, Sweden, and USA). Thirty cases were excluded from the analysis due to following reasons: Missing follow-up data, different pathology from ENKTL, and different treatment regimens containing anthracycline. Thus, 527 patients were analyzed, and male (n = 341) was predominant compared to female (n = 186). 70% of patients were ≤ 60 years at diagnosis whereas 30% was older than 60 years. Two-thirds of patients had stage I/II (n = 346) and nasal tract was most commonly involved extranodal site (n = 421, 80%). Bone marrow involvement was observed in 83 patients (16%), and distant lymph nodes were involved in 86 patients (16%). With a median follow-up of 45 months (IQR: 22-65 months), 306 patients (58%) were alive at the time of analysis and the event of progression-free survival occurred in 272 patients including relapse or progression (n = 187). The median OS was 76 months (95% CI: 51-101 months) and PFS was 32 months (95% CI: 20-45 months). The multivariate analysis for OS and PFS showed a significant association of four parameters with survival outcomes: age > 60, stage III/IV, distant lymph node involvement, and non-nasal tract involvement (P < 0.001). Thus, the prognosis of patients with age > 60, stage III/IV and distant lymph node involvement was poor, and patients who did not involve nasal tract also showed worse OS and PFS than patient with nasal tract involvement. Thus, we gave one score for each parameter. According to the sum of scores, patients with score 0 or 1 were grouped as low risk, score 2 was intermediate, and score 3 or 4 was high risk. This new risk model showed a strong association with OS and PFS (Figure 1). Among 328 patients who were initially evaluated for EBV DNA in blood, 189 patients (58%) showed detectable level of EBV DNA. The multivariate analysis including EBV DNA titer focused on these 328 patients showed that aforementioned four parameters and the presence of EBV DNA were independently associated with OS and PFS. Thus, we proposed another risk model for patients who had EBV DNA data with these five parameters consisting of low (score 0/1), low-intermediate (score 2), high-intermediate (score 3), and high risk (score 4/5).
Summary
Our multinational, multicenter retrospective study proposed a new prognostic model for newly diagnosed ENKTL patients who were treated with non-anthracycline based treatment. It consists of age > 60, stage III/IV, distant lymph node involvement, and no involvement of nasal tract. Our finding will be validated by currently ongoing study with an independent cohort including China.
Keyword(s): Lymphoma, NK-T cells, Prognostic factor
Session topic: Treatment and outcome in non-Hodgkin lymphomas
Abstract: S110
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 12:30 to 12.06.2015 12:45
Location: Room A7
Background
Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare type of non-Hodgkin lymphoma with poor prognosis because tumor cells are frequently resistant to anthracycline-containing chemotherapy such as CHOP due to expression of the multidrug-resistant p-glycoprotein. As a result, the treatment strategy for ENKTL has changed to non-anthracycline based regimens such as SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) with or without radiotherapy. Thus, concurrent chemoradiotherapy followed by non-anthracycline based chemotherapy is recommended for localized disease whereas intensified chemotherapy such as SMILE is for advanced disease. However, there is no proven prognostic model for ENKTL in the era of this new treatment strategy because previous prognostic models were developed by analyzing patients who were treated with CHOP or CHOP-like regimens.
Aims
This study is to explore risk factors for poor progression-free survival (PFS) and overall survival (OS) in ENKTL, and establish a prognostic model for ENKTL patients treated with non-anthracycline based treatment.
Methods
This is a retrospective cohort study using anonymized information from patients with ENKTL. The following criteria are required: (1) Patients diagnosed with ENKTL, nasal type between January 1, 1995 and December 31, 2012; (2) Patients treated with non-anthracycline based therapy as an initial treatment. The pathology of initial diagnosis was reviewed by designated pathologists.
Results
The data of 557 patients were from 32 hospitals from six Asian countries (Korea, Japan, Hong Kong China, Singapore, Taiwan, and Malaysia) and 6 hospitals from five Western countries (France, Germany, Denmark, Sweden, and USA). Thirty cases were excluded from the analysis due to following reasons: Missing follow-up data, different pathology from ENKTL, and different treatment regimens containing anthracycline. Thus, 527 patients were analyzed, and male (n = 341) was predominant compared to female (n = 186). 70% of patients were ≤ 60 years at diagnosis whereas 30% was older than 60 years. Two-thirds of patients had stage I/II (n = 346) and nasal tract was most commonly involved extranodal site (n = 421, 80%). Bone marrow involvement was observed in 83 patients (16%), and distant lymph nodes were involved in 86 patients (16%). With a median follow-up of 45 months (IQR: 22-65 months), 306 patients (58%) were alive at the time of analysis and the event of progression-free survival occurred in 272 patients including relapse or progression (n = 187). The median OS was 76 months (95% CI: 51-101 months) and PFS was 32 months (95% CI: 20-45 months). The multivariate analysis for OS and PFS showed a significant association of four parameters with survival outcomes: age > 60, stage III/IV, distant lymph node involvement, and non-nasal tract involvement (P < 0.001). Thus, the prognosis of patients with age > 60, stage III/IV and distant lymph node involvement was poor, and patients who did not involve nasal tract also showed worse OS and PFS than patient with nasal tract involvement. Thus, we gave one score for each parameter. According to the sum of scores, patients with score 0 or 1 were grouped as low risk, score 2 was intermediate, and score 3 or 4 was high risk. This new risk model showed a strong association with OS and PFS (Figure 1). Among 328 patients who were initially evaluated for EBV DNA in blood, 189 patients (58%) showed detectable level of EBV DNA. The multivariate analysis including EBV DNA titer focused on these 328 patients showed that aforementioned four parameters and the presence of EBV DNA were independently associated with OS and PFS. Thus, we proposed another risk model for patients who had EBV DNA data with these five parameters consisting of low (score 0/1), low-intermediate (score 2), high-intermediate (score 3), and high risk (score 4/5).
Summary
Our multinational, multicenter retrospective study proposed a new prognostic model for newly diagnosed ENKTL patients who were treated with non-anthracycline based treatment. It consists of age > 60, stage III/IV, distant lymph node involvement, and no involvement of nasal tract. Our finding will be validated by currently ongoing study with an independent cohort including China.
Keyword(s): Lymphoma, NK-T cells, Prognostic factor
Session topic: Treatment and outcome in non-Hodgkin lymphomas
Type: Oral Presentation
Presentation during EHA20: From 12.06.2015 12:30 to 12.06.2015 12:45
Location: Room A7
Background
Extranodal natural killer/T-cell lymphoma (ENKTL), nasal type, is a rare type of non-Hodgkin lymphoma with poor prognosis because tumor cells are frequently resistant to anthracycline-containing chemotherapy such as CHOP due to expression of the multidrug-resistant p-glycoprotein. As a result, the treatment strategy for ENKTL has changed to non-anthracycline based regimens such as SMILE (steroid, methotrexate, ifosfamide, L-asparaginase, and etoposide) with or without radiotherapy. Thus, concurrent chemoradiotherapy followed by non-anthracycline based chemotherapy is recommended for localized disease whereas intensified chemotherapy such as SMILE is for advanced disease. However, there is no proven prognostic model for ENKTL in the era of this new treatment strategy because previous prognostic models were developed by analyzing patients who were treated with CHOP or CHOP-like regimens.
Aims
This study is to explore risk factors for poor progression-free survival (PFS) and overall survival (OS) in ENKTL, and establish a prognostic model for ENKTL patients treated with non-anthracycline based treatment.
Methods
This is a retrospective cohort study using anonymized information from patients with ENKTL. The following criteria are required: (1) Patients diagnosed with ENKTL, nasal type between January 1, 1995 and December 31, 2012; (2) Patients treated with non-anthracycline based therapy as an initial treatment. The pathology of initial diagnosis was reviewed by designated pathologists.
Results
The data of 557 patients were from 32 hospitals from six Asian countries (Korea, Japan, Hong Kong China, Singapore, Taiwan, and Malaysia) and 6 hospitals from five Western countries (France, Germany, Denmark, Sweden, and USA). Thirty cases were excluded from the analysis due to following reasons: Missing follow-up data, different pathology from ENKTL, and different treatment regimens containing anthracycline. Thus, 527 patients were analyzed, and male (n = 341) was predominant compared to female (n = 186). 70% of patients were ≤ 60 years at diagnosis whereas 30% was older than 60 years. Two-thirds of patients had stage I/II (n = 346) and nasal tract was most commonly involved extranodal site (n = 421, 80%). Bone marrow involvement was observed in 83 patients (16%), and distant lymph nodes were involved in 86 patients (16%). With a median follow-up of 45 months (IQR: 22-65 months), 306 patients (58%) were alive at the time of analysis and the event of progression-free survival occurred in 272 patients including relapse or progression (n = 187). The median OS was 76 months (95% CI: 51-101 months) and PFS was 32 months (95% CI: 20-45 months). The multivariate analysis for OS and PFS showed a significant association of four parameters with survival outcomes: age > 60, stage III/IV, distant lymph node involvement, and non-nasal tract involvement (P < 0.001). Thus, the prognosis of patients with age > 60, stage III/IV and distant lymph node involvement was poor, and patients who did not involve nasal tract also showed worse OS and PFS than patient with nasal tract involvement. Thus, we gave one score for each parameter. According to the sum of scores, patients with score 0 or 1 were grouped as low risk, score 2 was intermediate, and score 3 or 4 was high risk. This new risk model showed a strong association with OS and PFS (Figure 1). Among 328 patients who were initially evaluated for EBV DNA in blood, 189 patients (58%) showed detectable level of EBV DNA. The multivariate analysis including EBV DNA titer focused on these 328 patients showed that aforementioned four parameters and the presence of EBV DNA were independently associated with OS and PFS. Thus, we proposed another risk model for patients who had EBV DNA data with these five parameters consisting of low (score 0/1), low-intermediate (score 2), high-intermediate (score 3), and high risk (score 4/5).
Summary
Our multinational, multicenter retrospective study proposed a new prognostic model for newly diagnosed ENKTL patients who were treated with non-anthracycline based treatment. It consists of age > 60, stage III/IV, distant lymph node involvement, and no involvement of nasal tract. Our finding will be validated by currently ongoing study with an independent cohort including China.
Keyword(s): Lymphoma, NK-T cells, Prognostic factor
Session topic: Treatment and outcome in non-Hodgkin lymphomas
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