First-Line Treatment and Survival of Stage I(E) Peripheral T-Cell Lymphoma in the Netherlands; A Nationwide Population-Based Cohort Study

Abstract Introduction: Peripheral T-cell lymphomas (PTCL) comprise a heterogenous group of mature T-cell neoplasms with generally an unfavorable prognosis. Presentation of PTCL with stage I(E) disease, according to the Ann Arbor classification, is uncommon. Clinical trials in diffuse large B-cell lymphoma (DLBCL) support the use of an abbreviated treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone combined with radiotherapy (combined modality therapy (CMT)) in case of stage I(E) disease. CMT in stage I(E) PTCL has been adapted in daily practice, but clinical trials are lacking. A recent population-based study conducted in Scandinavia indicated that the outcome in patients with limited stage PTCL is as poor as in patients with extensive disease. However, the outcomes of different treatment modalities were not analyzed. Aim: The aim of this nationwide population-based cohort study is to describe first-line treatment and outcome of patients with stage I(E) PTCL in comparison to advanced stage PTCL. Methods: All newly diagnosed patients ≥ 18 years with stage I(E) PTCL who were diagnosed in 1989-2018 were identified in the Netherlands Cancer Registry (NCR). Survival follow-up was available through February 1, 2021. The PTCL subgroups analyzed included anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL), enteropathy associated T-cell lymphoma (EATL) and peripheral T-cell lymphoma NOS (PTCL NOS). Patients were categorized according to treatment regimen, i.e. chemotherapy, chemotherapy followed by autologous stem cell transplantation (ASCT), radiotherapy, CMT, and no/other therapy. Calendar period analyses (1989-1999 and 2000-2018) were conducted to assess trends in primary therapy and overall survival (OS) over time. The calendar periods were defined according to the implementation of CMT in patients with limited stage DLBCL from approximately 2000 onward in the Netherlands. The primary endpoint was OS, defined as all-cause-death post-diagnosis. Results: From 1989 to 2018, 854 patients with a median age of 62 years were diagnosed with stage I(E) PTCL, accounting for 19% of all PTCL diagnoses. In stage I(E), the predominant PTCL subtype was PTCL NOS (40%, n=343). Furthermore, 26% (n=222) of patients were diagnosed with ALCL, 3% (n=28) with AITL, 11% (n=93) with EATL and 20% (n=168) with other histological subtypes. In contrast, for patients with advanced stage disease, 42% was diagnosed with PTCL NOS, 23% with ALCL, 24% with AITL, 6% with EATL and 5% with other histological subtypes . To evaluate treatment and survival outcome in patients with stage I(E) PTCL, patients with ALCL, AITL, PTCL NOS and EATL were included for further analyses (n=686). Patients with ALCL, AITL and PTCL NOS were most commonly treated with CMT (n=164; 28%) or chemotherapy only (n=154; 26%). Only 10 patients (1%) received chemotherapy followed by ASCT. The remaining patients were treated with either radiotherapy only (n=116; 20%) or received other/no therapy (n=149; 25%). More patients were treated with CMT in 2000-2018 as compared to 1989-1999 (36% versus 17%, p<0.01). Patients with EATL were most commonly treated with either chemotherapy only or other/no treatment (both n=45; 48%), while 3 patients (4%) received chemotherapy in combination with ASCT (n=2) or CMT (n=1). In EATL, no differences in treatment strategy were observed over time. Overall, 5-year OS for all stage I(E) PTCL was 52%. There was no significant difference in outcome between the two time periods (53% vs. 52%, p=0.92). EATL had a worse prognosis when compared to ALCL, AITL and PTCL NOS (5-year OS 15% vs. 58%, respectively; p<0.01). Five-year OS was significantly higher for patients with ALCL, AITL and PTCL NOS treated with CMT (71%) as compared to patients treated with either chemotherapy alone or with radiotherapy alone (52%, and 53%, respectively; p<0.01). Independent predictors for poor prognosis were higher age, male gender and EATL subtype whereas CMT was associated with a lower risk of mortality when evaluated for in multivariable analysis. Conclusions: For stage I(E) ALCL, AITL and PTCL NOS, 5-year OS is 58%. This compares favorably to the reported outcomes in advanced stage disease. EATL, even when presenting with limited stage disease, is associated with a very poor prognosis. CMT is associated with superior OS when compared to either chemotherapy or radiotherapy alone. Disclosures Van Der Poel: Roche, Janssen, Abbvie: Honoraria. Kersten: Kite/Gilead: Consultancy, Honoraria, Research Funding; BMS/Celgene: Consultancy; Miltenyi Biotech: Consultancy; Novartis: Consultancy, Honoraria; Roche: Honoraria; Takeda: Consultancy. Mutsaers: BMS: Consultancy; AstraZeneca: Research Funding. Woei-a-Jin: University Hospitals Leuven, Belgium: Current Employment; Recordati: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Kyowa Kirin: Research Funding.

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Limited-Stage Mantle Cell Lymphoma

Blood ◽

10.1182/blood.v128.22.5330.5330 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5330-5330 ◽

Cited By ~ 1

Author(s):

Ritsuro Suzuki ◽

Dai Chihara ◽

Naoko Asano ◽

Ken Ohmachi ◽

Tomohiro Kinoshita ◽

...

Keyword(s):

Research Funding ◽

Cell Lymphoma ◽

Clinical Stage ◽

Stage Iv ◽

Stage I ◽

Stage Ii ◽

Stage Iii ◽

Advanced Stage ◽

Limited Stage ◽

Stage Disease

Abstract [Background] Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma, characterized by the overexpression of cyclin D1 derived from t(11;14)(q13;q32) and poor prognosis. Most MCLs show nodal presentation, but also accompany extranodal involvement, such as bone marrow, peripheral blood or gastrointestinal tract. As a result, many MCLs present with advanced stage disease. Since only a small portion of patients show limited-stage disease, minimal data exist on treatment of patients diagnosed with limited stage disease. Nevertheless, the treatment strategy of MCL is recommended according to the clinical stage of limited- (stage I or non-bulky II) vs. advanced-stage, as well as other types of lymphoma. [Patients and methods] We recently collected 633 patient data of MCL (Chihara, et al. Ann Oncol 2015). Information of clinical stage was available in 626 patients. The patient data were retrospectively analyzed the by the clinical stage at initial presentation. [Results] The clinical stage was I in 24 patients (4%), II in 33 (5%), III in 70 (11%), and IV in 499 (80%). Only one patient presented with bulky stage II. Detailed demographic information by the clinical stage are listed in Table. Age and sex were not significantly different by clinical stage. Limited stage patients were associated with better performance status (PS), less B symptoms, no extranodal involvement, and lower lactate dehydrogenase (LDH) level and white blood cell (WBC) count. Most patients in any stage were treated with cytotoxic chemotherapy, but more patients in limited stage received radiotherapy. The proportion of high-dose cytarabine (HDCA)-containing regimen over CHOP/CHOP-like was higher in advanced stage patients. Complete and overall response rates were 92% and 96% in stage I, 58% and 94% in stage II, 66% and 86% in stage III, and 52% and 82% in stage IV, respectively (P = 0.02). However, the higher response rate in limited stage patients did not translate into better prognosis. The median survival was 11.0 years in stage I, 13.4 years in stage II, 11.5 years in stage III, and 5.6 years in stage IV (Figure). The prognosis was not significantly different among patients with stage I, II, and III (P = 0.33). [Conclusion] Prognosis of limited-stage MCL was almost similar to that of stage III MCL. Although the present study includes several limitations including a retrospective nature and limited number of patients, prognosis of patients with limited-stage MCL was not satisfactory. The significance of radiotherapy, as well as the optimal choice of chemotherapy, for limited-stage MCL needs re-evaluation. Table Table. Figure Figure. Disclosures Suzuki: Chugai: Honoraria; Kyowa Hakko kirin: Honoraria; Bristol-Myers Squibb: Honoraria. Asano:Jannsen: Honoraria; Chugai: Honoraria. Kinoshita:Ono: Research Funding; Gilead: Research Funding; Zenyaku: Honoraria, Research Funding; Takeda: Research Funding; Chugai: Honoraria, Research Funding; Eisai: Honoraria, Research Funding; Solasia: Research Funding; Janssen: Honoraria; Kyowa Kirin: Honoraria. Suzumiya:Chugai: Honoraria, Research Funding; Astellas: Research Funding; Eisai: Honoraria, Research Funding; Takeda: Honoraria; Toyama Chemical: Research Funding; Kyowa Hakko kirin: Research Funding. Ogura:SymBio Pharmaceuticals: Consultancy, Honoraria; Celltrion, Inc.: Consultancy, Honoraria.

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Management of NK/T-Cell Lymphoma, Nasal Type

Journal of Oncology Practice ◽

10.1200/jop.18.00719 ◽

2019 ◽

Vol 15 (10) ◽

pp. 513-520 ◽

Cited By ~ 2

Author(s):

Pamela B. Allen ◽

Mary Jo Lechowicz

Keyword(s):

T Cell ◽

Epstein Barr Virus ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Nasal Type ◽

Barr Virus ◽

Limited Stage ◽

Stage Disease ◽

Nk T Cell ◽

Epstein Barr

Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a rare peripheral T-cell lymphoma associated with Epstein-Barr virus. It most often presents as limited-stage disease in patients of East Asian descent with a palatal deformity caused by erosion of the tumor through the hard palate. Limited-stage disease is often curable with the use of l-asparaginase–based chemotherapy and high-dose radiation therapy. Obtaining an accurate diagnosis is essential, because treatment with standard lymphoma regimens and omission of radiation severely compromise the likelihood of long-term survival. Conversely, patients with advanced disease have a poor prognosis and are recommended for asparaginase-based chemotherapy followed by consolidation with autologous transplantation as a potentially curative approach. Progress often has been hampered by the rarity of this disease. However, discovery of common genetic alterations in pathways that promote growth and inhibit apoptosis, and actionable markers such as CD30 (among others), have begun to broaden the availability of novel drugs (eg, targeted therapies). There is also cautious optimism about immunotherapies, such as checkpoint blockade and novel cellular therapies that target Epstein-Barr virus. Advances in treatment and understanding of the genetic landscape of this disease offer hope for improved treatment outcomes.

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NK/T Cell Versus Peripheral T Cell Lymphoma: Significant Differences in Clinical Characteristics and Survival.

Blood ◽

10.1182/blood.v108.11.4600.4600 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4600-4600

Author(s):

Soon-Thye Lim ◽

Fei Gao ◽

Lay-Cheng Lim ◽

Richard Quek ◽

Daryl Lim ◽

...

Keyword(s):

T Cell ◽

Who Classification ◽

Cell Lymphoma ◽

Univariate Analysis ◽

Prognostic Significance ◽

T Cell Lymphoma ◽

Stage I ◽

Advanced Stage ◽

Peripheral T Cell Lymphoma ◽

Nk T Cell

Abstract Background: To compare the clinico-pathologic characteristics and prognosis of Natural Killer/T cell lymphoma (NK/TL) with peripheral T cell lymphoma (PTCL). Methods: A total of 556 resident patients (pts) with lymphoma were treated in the departments of medical oncology and hematology in an Asian institution from 2000 to 2005. Of these pts, 71 (12.8%) had NK/TL or PTCL and were included in this analysis. Pathology was centrally reviewed and classified according to the WHO classification. Results: NK/TL and PTCL comprised of 4.7% (26/556) and 7.9% (45/556) of all cases. Of the PTCL cases, histology was PTCL-NOS in 21, anaplastic large cell in 12 (5 were ALK-1 positive) and angioimmunoblastic T cell in 8 pts. Subcutaneous panniculitis T cell and γ/δ T cell lymphoma accounted for one case each. There were no significant differences between the two groups of pts in terms of sex, performance status, extranodal involvement and LDH level at presentation. However, more patients with NK/TL presented with stage I/II disease (65% vs. 31%, p=0.003). Among pts with NK/TL, 17 (65%) received CHOP-based chemotherapy, 4 received radiation alone and 5 received palliative chemotherapy. In the PTCL group, 39 (87%) received CHOP-based chemotherapy, 2 received radiation alone and 3 received palliative treatment only. Compared to PTCL, NK/TL was associated with a significantly inferior rate of complete remission (27% vs. 58%, p=0.01) and inferior overall survival (5 vs. 28.4 mos, p=0.001). Although age > 60, ECOG ≥ 2, elevated LDH, advanced stage, IPI ≥ 2 and NK/T cell histology were each associated with decreased survival on univariate analysis, only NK/T cell histology and advanced stage were independently associated with decreased survival (see table 1). Conclusions: Contrary to expectation, the incidence of PTCL based on WHO classification in this Asian series is not higher than that reported in Western series. Compared to PTCL, the NK/T subtype is associated with a paricularly inferior prognosis and overrides the prognostic significance of IPI. These data suggest that NK/TL should be considered as a seperate entity and should not be considered together with other subtypes of T cell lymphoma in clinical trials. Table 1. NK/TL vs. PTCL: Univariate and Multivariate Analyses Univariate Analysis Multivariate Analysis Median (yr) P Hazard Ratio 95% CI P Male vs. Female 1.03 vs. Not reached 0.06 0.62 0.28 to 1.40 0.25 Age<60 vs. ≥ 60 2.37 vs. 0.51 0.01 1.41 0.70 to 2.83 0.33 ECOG 0/1 vs. ≥ 2 1.99 vs. 0.36 0.002 1.52 0.63 to 3.65 0.354 LDH normal vs. High Not reached vs. 0.75 0.03 1.29 0.53 to 3.13 0.57 Stage I/II vs. III/IV 1.99 vs. 1.41 0.16 2.91 1.17 to 7.2 0.02 IPI 0/1 vs. ≥ 2 Not Reached vs. 0.42 0.002 2.22 0.82 to 5.99 0.12 PTCL vs. NK/TL 2.37 vs. 0.42 0.001 5.8 2.36 to 14.24 <0.001

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Population-Based Analysis of Elderly Patients (>70 YEARS) with Peripheral T-CELL Lymphoma: A Results from Czech Lymphoma Study Group (CLSG) Registry

Blood ◽

10.1182/blood.v128.22.3000.3000 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3000-3000 ◽

Cited By ~ 1

Author(s):

Andrea Janikova ◽

Robert Pytlik ◽

Pavel Klener ◽

Zbynek Bortlicek ◽

Vit Campr ◽

...

Keyword(s):

T Cell ◽

Elderly Patients ◽

Research Funding ◽

Cell Lymphoma ◽

Large Cell ◽

Population Based ◽

T Cell Lymphoma ◽

First Line ◽

Peripheral T Cell Lymphoma ◽

Age Related

Abstract INTRODUCTION: Peripheral T-cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphomas with usually poor prognosis. Age was identified as the independent risk factors in many studies. Elderly patients suffer from comorbidities, impaired organ functions, and poor performance status resulting in worse tolerance of therapy and its efficacy. Data on outcome, prognosis and treatment efficacy for elderly patients with PTCLs are sparse. METHODS: We used data of 941 newly diagnosed PTCLs registered into CLSG database between January 1999 and March 2015 with last follow-up in February 2016. CLSG database covers approximately 85% of all newly diagnosed NonHodgkin´s lymphomas (NHLs) in Czech Republic. For the analysis, 208 patients with age >70 years at diagnosis were selected. RESULTS: Totally, PTCLs accounted for about 8.7% (454/5210) patients of all NHLs in population younger 60 years, but only about 5.8% (208/3561) NHL patients older 70 years. Median age was 76ys (71-91ys), 94 (45%) were women, lactate dehydrogenase (LDH) was elevated in 130/208 (62.5%) pts., ECOG ≥2 had 80 (38%) pts., and advanced clinical stage III-IV presented 132/208 (63.5%) pts. We identified following PTCL subtypes: PTCL-NOS (Peripheral T-cell lymphoma not otherwise specified) 89/208 (43%), Anaplastic large cell lymphoma (ALCL) 34/208 (16.3%), Cutaneous Anaplastic large cell lymphoma (C-ALCL) 10/208 (4.8%), Mycosis fungoides/ Sézary syndrome (MF/SS) together 29/208 (14%), NK/T nasal lymphoma (NK/T) 2/208 (1%), Angioimmunoblastic lymphoma (AITL) 17/208 (8.1%), Cutaneous CD30+ T lymphoproliferative disease 1/208 (0.5%), T-lymphoblastic lymphoma/leukemia (T-LBL) 3/208 (1.4%), T-cell lymphoma without specification (T-NHL) 17/208 (8.1%). Distribution of PTCL subtypes changed significantly with age. There was higher proportion of PTCL-NOS (43% vs. 34%; p.001) and MF/SS (14% vs. 4.8%; p<.001) in elderly patients (>70ys) compared to younger cohort (≤70ys; n=725). Contrary, percentage of ALCL (16.3% vs. 27%; p<.001) with main difference in ALK+ cases (2% vs. 11%; p<.001), and NK/T (1% vs. 5%; p.003) was lower in elderly PTCLs, whereas the incidence of AITL (8.1% vs. 6.6%) or EATL (3.4% vs. 3%) was similar in both age subgroups. For the whole cohort of PTCLs (>70ys), the 5-year overall survival (OS) was 30% and 5-year progression free survival (PFS) was 21% regardless of subtype or stage. Progression is fatal event in elderly patients with median survival about 8 months only. There were significant survival differences between patients (>70ys vs. ≤70ys) according to PTCL subtype; PTCL-NOS 5 yr-OS 23% vs. 43% (p.00001), ALCL ALK+ 5-yr OS not reached vs. 79% (p.01), ALCL ALK- 5 yr-OS 24% vs. 50% (p.001). Patients with AITL or EATL showed no age-related survival differences. First-line chemotherapy was administered in majority of cases (67%); CHOP-like regimen was given in 78 (37%) pts., COP-like in 44 (21%) pts., and other chemotherapy in 18 (9%) cases. Local therapy (surgery, radiotherapy) was administered in first line in 17 (8%) pts., no or palliative therapy (corticoids) was given in 34 (17%) pts., initial therapy was unknown in 17 (8%) cases. We compared two subgroups of patients according to first line chemotherapy CHOP (n=75) vs. COP (n=41). Median age was 74ys (71-84) vs. 79ys (71-89), high IPI was presented in 29% vs. 50% of patients (p.001). Complete response (CR) was achieved in 35/75 (47%) CHOP treated patients, and in 7/41 (17%) patients managed with COP (p.001). Contrary, there were 12/75 (16%) progression in CHOP arm compared to 10/41 (24%) COP treated pts. Five-year OS was 28% vs. 15% better in CHOP group (p.029) and 5-yr PFS 25% vs. 10%, respectively. CONCLUSIONS: In population-based analysis of adult Caucasian PTCL patients, we identified mild decreasing incidence with age. There were significant age-related distribution differences of PTCL subtypes with shift to preponderance of PTCL-NOS, Mycosis fungoides, and NK/T nasal lymphoma in elderly. Worse survival in elderly PTCLs in comparison to younger patients was evident especially for PTCL-NOS and ALCL subtypes. Despite the baseline differences (COP managed pts. had higher IPI), there is tendency that anthracycline-based chemotherapy (CHOP) brings better results with higher proportion of CR and lower progression/relapse rate projected in longer survival. Disclosures Belada: Seattle Genetics: Research Funding. Mayer:AOP Orphan Pharmaceuticals: Research Funding; Novartis: Research Funding.

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Failure to Achieve CR with First-Line Treatment Is the Primary Cause of Treatment Failure in T-Cell Lymphoma: The Princess Margaret Cancer Centre Experience

Blood ◽

10.1182/blood.v128.22.3005.3005 ◽

2016 ◽

Vol 128 (22) ◽

pp. 3005-3005

Author(s):

Umberto Falcone ◽

Melania Pintilie ◽

Ri Wang ◽

Vishal Kukreti ◽

John G. Kuruvilla ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Primary Treatment ◽

T Cell Lymphoma ◽

Line Treatment ◽

First Line ◽

Limited Stage ◽

Stage Disease ◽

First Line Treatment

Abstract Introduction: T-cell lymphomas (T-NHL) represent rarer entities compared to B-NHL, accounting for 5% -10% of NHL in Western countries and 15%-20% in Asia. They are divided into clinico-pathologic subtypes based on etiology, morphology, and clinical behavior. Because of the rarity and the lack of specific histologic features for the different subtypes, the diagnosis is difficult and clinical picture is usually very helpful to establish the diagnosis. We conducted a retrospective analysis of patients (pts) with T-NHL treated at our Centre, with the purpose of studying overall outcome and possible prognostic factors, including histologic subtypes, from our database. Patients and methods: Consecutive T-NHL pts (excluding Adult T-cell leukemia/lymphoma, NK/T NHL, and primary cutaneous T-NHL), receiving primary treatment at the Princess Margaret Cancer Centre (PMCC) between 2001-2014 were included. Data were extracted from a prospective patient database and the medical record regarding baseline characteristics, treatment, response and outcome. Response assessment was with CT imaging as per 1999 Working Group criteria. Results: Of a total of 2155 pts with aggressive histology NHL treated at PMCC between 2001-2014, 2031 pts had B-NHL and 124 (5.7%) T-NHL. Median age was 56 years (18-90), male/female ratio: 2.4; 63% presented with advanced stage (III-IV) disease, 22% had bone marrow involvement; 63% had elevated LDH and 44% had B symptoms. Observed subtypes were: Peripheral T-cell lymphoma, NOS 58 pts (PTCL NOS, 47%), Anaplastic large cell lymphoma, ALK-negative 16 pts (ALCL-ALK-, 13%), ALCL, ALK-positive 22 pts (ALCL-ALK+, 18%), Angioimmunoblastic T-cell lymphoma 13 pts (AITL, 10.5%), Enteropathy-associated T-cell lymphoma 7 pts (EATL, 5.6%), Hepatosplenic T-cell lymphoma 8 pts (HSTCL, 6%). 105/124 pts (85%) received induction chemotherapy; CHOP-like regimens were used in 94 pts (90%), and involved field radiation therapy (RT) was included in primary treatment in 24 pts (19%). Nineteen pts were treated palliatively, 5 pts with RT alone, 14 pts received palliative chemotherapy or supportive care only. Complete response (CR) was obtained in 63/105 pts (60%; Table 2), PR in 2 pts (1.9%) and 40 pts had no response or progressive disease (SD and PD; 38%). Considering together the most common subtypes (ALCL-ALK+/-, AITL, PTCL NOS), CR rate was 84% in limited stage vs 52% in advanced stage disease. Among patients with CR, 24 relapsed (38%). Fourteen pts received autologous stem cell transplant (8 at relapse, 6 for PD); 7/14 (50%) were alive at last follow-up. At a median follow-up of 5.3 years, 57/124 (46%) pts are alive. Cause of death was T-NHL in 50/124 (40%) pts. Two pts died of second malignancy (1.6%). Median overall survival (OS) and progression-free survival (PFS) were 4.57 years (95%CI: 2.23-9.53; 5yOS: 48%) and 1.5 years (0.87-3.17; 5yPFS: 37%), respectively (Table 2). For pts with limited stage disease median PFS was 4.57 years (5yPFS: 49%) and median OS 10.0 years (5yOS: 62%), while for pts with stage III/IV, median PFS was 0.82 years (5yPFS: 31%) and OS 1.81 years (5yOS: 38%). Median OS for pts who did not experience relapse (39/63; 62%) was 13.38 years (95%CI: 9.53-NA; 5yOS: 93%) vs 3.12 years (95%CI: 1.69-4.07 years; 5yOS: 25%) in pts who had relapse after CR1 (p<0.001). Pts failing to achieve CR (PR, SD, PD) had a very poor outcome with median OS 1.15 years (95%CI: 0.62-1.32 years; 5yOS: 17%). For PTCL NOS pts, outcomes were poor while those with ALCL had more favorable results regardless of ALK status (Table 2). Conclusions: Failure to achieve CR with first-line treatment was the main cause of treatment failure in patients with T-NHL treated with anthracycline-based chemotherapy. Patients with limited stage lymphoma and with ALCL ALK+/- subtypes have more favorable outcomes. For PTCL NOS, the most common subtype, and less common entities (HSTCL, EATL), results are poor and new induction strategies are needed. Disclosures Kukreti: Celgene: Honoraria; Amgen: Honoraria; Lundbeck: Honoraria.

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Radiation Therapy In Peripheral T-Cell Lymphoma Of The Head and Neck

Blood ◽

10.1182/blood.v122.21.1795.1795 ◽

2013 ◽

Vol 122 (21) ◽

pp. 1795-1795 ◽

Cited By ~ 2

Author(s):

Annemarie T. Fernandes ◽

Jakub Svoboda ◽

Sunita D. Nasta ◽

Lynn D. Wilson ◽

John P. Plastaras

Keyword(s):

Overall Survival ◽

Radiation Therapy ◽

T Cell ◽

Marital Status ◽

Head And Neck ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Stage I ◽

Peripheral T Cell Lymphoma ◽

Stage Disease

Abstract Introduction The role of radiation therapy in peripheral T-cell lymphoma (PTCL) is not well established. While the NCCN guidelines recommend combined modality treatment with consolidative radiation therapy after chemotherapy for localized (stage I and II) disease, the data supporting this recommendation is lacking and is extrapolated from B-cell lymphoma. Methods This is a retrospective analysis of outcome in patients with non-cutaneous peripheral T-cell lymphoma of the head and neck from the Surveillance, Epidemiology and End Results (SEER) database diagnosed between 1981-2010. Survival was estimated by Kaplan-Meier estimates using the log-rank test. Univariate and multivariable analyses were performed using Cox regression analysis. Results Of the 307 patients analyzed, 130 (43%) underwent radiation therapy. The median age was 59 years old, 60.3% were male, 73.9% were Caucasian and the median year of diagnosis was 2004. The majority of patients had PTCL, Not Otherwise Specified (74.3%), followed by anaplastic large cell histology (22.2%). Patients were grouped as stage I (47.2%), stage II (29.9%) and stage III/IV (22.8%). Head and neck sites included the nasal cavity (28.3%), oropharynx (25.7%), oral cavity (21.2%), salivary gland (11.7%), nasopharynx (7.8%) and larynx/hypopharynx (5.2%). The median follow-up was 54 months for survivors. Radiation therapy was associated with a higher 5-year overall survival in all patients (56.7% vs. 38.4%, p=0.001), patients with stage I disease (63.4% vs. 53.4%, p=0.036) and patients with stage II disease (60.8% vs. 36.3%, p=0.034), see Figure 1. Radiation therapy was not associated with a difference in overall survival in patients with stage III/IV disease (p=0.91). Univariate analysis demonstrated that age, stage, radiation therapy and marital status were predictive of overall survival, but sex, and race were not. The year (p=0.93) or decade of treatment (p=0.67) did not impact overall survival. On multivariable analysis, increasing age (HR: 1.02, p<0.001), increasing stage (HR: 1.42, p=0.004), radiation therapy (HR: 0.60, p=0.011) and marital status of not married (HR: 1.49, p=0.035) remained statistically significant predictors of overall survival. An additional analysis was performed excluding patients who survived less than 3 months to account for mortality related to disease progression or chemotherapy toxicity. After excluding these 45 patients, radiation therapy was still associated with increased overall survival in all patients (p<0.001) and in patient with limited stage disease (p=0.021). Conclusions The integration of local radiation therapy to the treatment of PTCL of the head and neck may improve overall survival in patients with limited stage disease. Disclosures: No relevant conflicts of interest to declare.

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Allogeneic Transplant Outcomes for T-Cell Lymphomas: A Single Center Analysis

Blood ◽

10.1182/blood-2020-140188 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 20-21

Author(s):

Thomas Luo ◽

Timothy S. Fenske ◽

Mehdi Hamadani ◽

Parameswaran Hari ◽

Nirav N. Shah

Keyword(s):

T Cell ◽

Research Funding ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Rank Test ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Log Rank Test ◽

Stage Disease ◽

Relapse Rates

Introduction T-Cell Lymphoma (TCL) encompasses a wide range of lymphoid neoplasms that make up 10-20% of all non-Hodgkin lymphomas. Due to the heterogeneity of the disease compared with B-cell lymphomas, treatment algorithms vary widely. Autologous and allogeneic hematopoietic cell transplant (allo-HCT) have been utilized both in the frontline setting as a consolidative treatment and in the relapsed/refractory setting. Limited studies have reported that patients undergoing allo-HCT after salvage chemotherapy can achieve five-year overall survival (OS) rates above 60% (Kamarajah et al.). However, there remains a significant risk of relapse and non-relapse mortality in these patients, which has not been fully characterized. In this study, we evaluate outcomes of patients with TCL who have undergone allo-HCT. Methods We performed a retrospective, single center analysis of adult patients who received an allo-HCT with a diagnosis of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS), cutaneous T-cell lymphoma (CTCL), anaplastic large cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL) since 2008. Patients with concurrent malignancies were excluded. Baseline characteristics were measured using standard descriptive statistics. The Kaplan-Meier methodology was used to calculate the primary outcome, OS, which was estimated from date of transplant to date of death. Secondary outcomes included progression free survival (PFS), relapse rates, and incidence of acute and chronic graft-versus-host disease (GVHD) after transplant. A log-rank test was used to evaluate the impact of patient level variables on OS. STATA version 13.1 (College Station, TX) was used for analysis. Results We identified a total of 23 patients who met the criteria (Table 1). The majority of patients carried a diagnosis of PTCL-NOS (n=11) followed by AITL (n=8). The median age at transplant was 56 years and most patients were male (74%). The Hematopoietic Cell Transplant-Comorbidity Index (HCT-CI) score was ≥3 in 52% of patients (n=12) and Karnofosky Performance Status (KPS) at transplant was <90% in 78% (n=18). Most patients had advanced-stage disease at diagnosis and 35% (n=8) had a history of prior autologous HCT. 83% underwent allo-HCT for relapsed/refractory TCL (n=19), while the remaining received it as a consolidative procedure in first response. 61% of patients had residual disease entering transplant (n=14). Reduced intensity conditioning was used in 83% (n=19) of patients while the remaining received a myeloablative regimen. The median OS (Figure 1A) and PFS (Figure 1B) at 5 years was not reached in this cohort; furthermore, 74% of patients were alive one year post-transplant. 17% relapsed with their primary disease (n=4) and in total 9 patients have died since transplant, the majority from transplant related complications. 52% of patients had acute GVHD; similarly, 52% had chronic GVHD. Using the log-rank test, we found no difference in OS by donor type, conditioning intensity, stage at diagnosis, KPS<90%, prior autologous transplant, pre-transplant disease status, International Prognostic Index (IPI)≥3, and indication for transplant. Patients with HCT-CI ≥3 trended towards worse OS (p=0.09). Conclusion In the era of novel agents and cellular therapies, the role of allo-HCT in hematological malignancies must be redefined. While treatment options have expanded significantly in B-cell lymphomas, the same diversity of options is not available in TCLs, especially in the relapsed/refractory setting. We demonstrate here excellent outcomes in a small cohort of patients who mostly underwent allo-HCT for relapsed TCL. Despite several adverse characteristics (low KPS, elevated HCT-CI, advanced-stage disease) post-transplant relapse rates were low and both the 1-year OS and 5-year PFS/OS are encouraging and suggest that this modality of therapy continues to be relevant in the modern era. The apparent plateau in PFS and OS indicates that, even in this poor prognosis group of patients, allo-HCT provides a curative intent option. New strategies to ameliorate transplant-related complications could improve survival further. Disclosures Fenske: Medical College of Wisconsin: Current Employment. Hamadani:ADC Therapeutics: Membership on an entity's Board of Directors or advisory committees; Sanofi Genzyme, AstraZeneca: Speakers Bureau; Janssen R&D; Incyte Corporation; ADC Therapeutics; Celgene Corporation; Pharmacyclics, Omeros, AbGenomics, Verastem, TeneoBio: Consultancy; Takeda Pharmaceutical Company; Spectrum Pharmaceuticals; Astellas Pharma: Research Funding. Hari:Incyte Corporation: Consultancy; Amgen: Consultancy; Janssen: Consultancy; GSK: Consultancy; Takeda: Consultancy; BMS: Consultancy. Shah:Lily: Consultancy, Honoraria; Verastim: Consultancy; TG Therapeutics: Consultancy; Miltenyi Biotec: Honoraria, Research Funding; Incyte: Consultancy; Celgene: Consultancy, Honoraria; Kite Pharma: Consultancy, Honoraria; Cell Vault: Research Funding.

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A Multicenter Retrospective Analysis of Clinicopathologic Features of Monomorphic Epitheliotropic Intestinal T-Cell Lymphoma

Blood ◽

10.1182/blood-2018-99-117880 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2909-2909

Author(s):

Jun Ho Yi ◽

Lee Gyeong-Won ◽

Young Rok Do ◽

Hong Jung Yong ◽

Cheolwon Suh ◽

...

Keyword(s):

T Cell ◽

Retrospective Analysis ◽

Research Funding ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Stage I ◽

Prior History ◽

Clinicopathologic Features ◽

Presenting Symptoms ◽

Frequent Site

Abstract Introduction: Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a provisional entity in the 2017 WHO classifications of the lymphoid neoplasms, as it was found that features of MEITL differed from those of enteropathy-associated T-cell lymphoma. It is now considered that MEITL is more prevalent in Asia, and almost all cases of intestinal T-cell lymphoma in Asians might be MEITL. To further elucidate the clinicopathologic features of this new disease entity, we carried out a multicenter, retrospective analysis from 9 tertiary institutes in Korea. Patients and methods: A total of 38 patients who were diagnosed with MEITL between 2002 and 2017 from 9 institutes were included in the analysis. Medical records including age, sex, stage, presenting symptoms, laboratory findings, primary sites, and treatment outcomes were collected. The histopathologic diagnoses were centrally-reviewed by experienced lymphoma histopathologists. The primary end-point of the analysis was overall survival (OS). Results: The median age of the patients was 59 (range, 20 - 84) and 27 patients (71.1%) were male. None of the patients had prior history of Celiac disease. Thirty one patients (81.5%) were stage I-II by the Ann-Arbor classifications, and 28 patients (73.7%) were stage I-II1&2 by the Lugano classifications. The most frequent site of involvement was jejunum (N = 20) followed by ileum (N = 17), and 11 patients had multiple site involvement. In line with the previous reports, most cases expressed CD8 (77.1%) and CD56 (92.1%), and did not expressed CD30 (5.3%), and EBER (6.9%). T-cell intracellular antigen was positive in 14 out of 17 cases (82.4%). The median progression-free survival was 6.9 months (95% CI 4.2 - 9.6), and the median OS was 14.8 months (3.0 - 26.6). Thirty one patients (81.6%) received surgery, and 34 patients (89.5%) received chemotherapy. CHOP (N = 28) was the most frequently used regimen followed by CHOEP (N = 3), and ICE, IMVP-16, and EPOCH (N = 1 each). Complete response (CR) rate was 47.1%, and 14 patients had undergone autologous stem cell transplantation (ASCT). Relapse or progression was documented in 22 cases, and the most frequent site was the primary site (N = 20). Of note, relapse at central nervous system was found in 4 cases. Older age (≥ 55 years), advanced Lugano stage (IIE~IV), not achieving CR, and not receiving ASCT were associated with adverse OS. Conclusion: Although most patients had limited stage, the clinical outcomes of MEITL patients were dismal. While the optimal management of MEITL remains undetermined, achieving CR and consolidative ASCT seem to be essential. In addition, considering the frequent local failure, as well as the CNS relapse, novel therapeutic approaches are required to improve survival. Figure. Figure. Disclosures Kim: Mundipharma: Research Funding; Merck: Research Funding; Celgene: Research Funding; Takeda: Research Funding; Roche: Honoraria, Research Funding; Kyowa-Kirin: Research Funding; Eisai: Honoraria, Research Funding; J&J: Research Funding; Celltrion: Honoraria, Research Funding; Novartis: Research Funding.

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Complete Responses with Denileukin Diftitox in Cutaneous T-Cell Lymphoma Studies.

Blood ◽

10.1182/blood.v114.22.3745.3745 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3745-3745

Author(s):

Francine Foss ◽

Madeleine Duvic ◽

Elise A. Olsen ◽

Anna Kozlovski

Keyword(s):

Clinical Trials ◽

T Cell ◽

Cell Lymphoma ◽

Interleukin 2 ◽

T Cell Lymphoma ◽

Stage I ◽

Advanced Stage ◽

Cutaneous T Cell Lymphoma ◽

Denileukin Diftitox ◽

Significant Difference

Abstract Abstract 3745 Poster Board III-681 Cutaneous T-cell lymphoma (CTCL) is a disorder of CD4+ helper T-cells with manifestations in the skin, nodes, and, in advanced stages, blood and visceral sites. For many patients, the clinical course of the disease is chronic and progressive, despite multiple therapeutic interventions. To date, are few controlled clinical trials which demonstrate durable complete responses (CR) in advanced stage patients. Denileukin diftitox (DD) is a recombinant fusion protein targeting interleukin-2 receptor which has demonstrated efficacy in early and advanced stage CTCL with response rates of 30% and 44% in two clinical trials of CTCL pts with Stage Ib-IVA relapsed and refractory CTCL or Stage I-III disease, ≤3 prior therapies respectively. In these trials, patients (pts) were randomized to receive DD at a dose of either 9 or 18 ug/kg/d daily x 5 every 21 days. Another rollover trial enrolled pts who had progressed after prior response with DD (N=29) or were CD25- (N=36); all pts in the rollover trial were treated with DD at 18ug/kg dose. Of 263 intent-to-treat pts in these trials, 227 had CD25+ skin infiltrates by immunohistochemistry (IHC) confirmed by a reference pathologist and 36 were CD25-. Overall, 24 (9.1%) pts attained durable complete response (CR). The median age of the responders was 59, and 12 CR pts were over age 60. Of the CR group, 15 pts had early stage (I-IIa) disease and 9 had advanced stage (IIb-IV) CTCL. The mean prior therapies was 3.6 with 37% of patients having received >3 therapies. Of the 24 CR pts, 21 were CD25+ and 3 were CD25-. Two CR were pts who had previously responded to DD in an earlier clinical trial. Of all pts receiving 9 ug/kg dose (N=80), there were 6 (7.5%) CR; for all pts receiving 18 ug/kg dose (N=183), there were 18 (9.8%) CR. There was no significant difference frequency of CR between the 9 and 18 ug/kg groups (P=0.56) or between the CD25+ (N=118) and CD25- (N=36) pts treated at 18 ug/kg dose (P=0.64). CR rate was similar between the early and advanced stage patients (10.7% vs 8.9% respectively). The median time to response was 53.5 vs 41days for CD25+ pts treated in the 9 and 18 ug/kg groups respectively, and 43 days for the CD25- group. The response durations ranged from 57 days to >1325 days in the CD25+ and 190-400 days in the CD25- groups. Of the 24 CR, 7 have progressed as of the time of the analysis and 17 remain in CR. The overall median PFS at the time of analysis has not been reached (range 169-1388+ days). Of the 24 CR, 3 pts had hypersensitivity reactions and 3 had capillary leak syndrome associated with DD treatment. In summary, these studies demonstrate clinical benefit of DD with CR in both early and advanced CTCL at both 9 and 18 ug/kg doses and with durable responses in a small number of pts whose malignant lymphocytes were CD25- by ICH. Disclosures: Foss: Eisai : Speakers Bureau. Olsen:Eisai: Research Funding. Kozlovski:Eisai Pharm: Employment.

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