Peripheral T-cell Lymphoma NOS Research Articles

Circulating Lymphoma Cells in Mycosis Fungoides/Sezary Syndrome Show Heterogeneity of the Cell-of-Origin and Variable PD-1 Expression By Flow Cytometric Analysis

Introduction: Mycosis fungoides (MF) is an epidermotropic primary cutaneous T-cell lymphoma. Its leukemic variant is recognized as Sezary syndrome (SS), although a study suggests that MF and SS may be distinct entities arising from different T-cell subsets; effector memory T-cells and central memory T-cells, respectively (Campbell JJ et al. Blood. 2010;116(5):767-771). Recent studies show bright PD-1 (T follicular helper (TFH)-like), and CD25/FOXP3 (Treg-like) expression in a subset of MF/SS cases by immunohistochemistry, and these findings raise the possibility that the cell-of-origin of MF/SS may be heterogeneous (Cetinozman F et al. Arch Dermatol. 2012;148(12):1379-1385, Prince HM et al. J Am Acad Dermatol. 2012;67(5):867-875, Satou A et al. Histopathology. 2016;68(7):1099-1108). In order to address this question comprehensively, we evaluated the expression levels of PD-1 on lymphoma cells of MF/SS patients by flow cytometry in peripheral blood (PB), and the results were compared to other T-cell lymphomas including angioimmunoblastic T-cell lymphoma (AITL). We also performed extensive flow cytometric immunophenotyping to algorithmically assess cell-of-origin of MF/SS with a subset of patients (Maecker HT et al. Nat Rev Immunol. 2012;12(3):191-200).Methods: Patients who were diagnosed with T-cell lymphoma at Memorial Sloan Kettering Cancer Center between August 2015 and August 2018, and have circulating lymphoma cells in PB were selected for this study. Diagnosis of MF/SS was confirmed by skin biopsy along with the clinical presentation. PD-1 expression levels on lymphoma cells in PB were evaluated by 10-color flow cytometry including anti-CD279 (PD-1) antibody. Immunophenotyping to assess cell-of-origin of lymphoma cells (T-cell subset analysis) was performed with 3 tube/10-color flow cytometry, using the following antibodies: CD3, CD4, CD8, CD25, CD27, CD45RA, CD45RO, CD127, CD279, HLA-DR, CCR4, CCR6, CCR7, and CXCR3.Results: Our study group is composed of 82 patients, including 34 MF/SS, 22 AITL, 2 anaplastic large cell lymphoma, ALK-negative (ALCL, ALK-), 8 adult T-cell leukemia/ lymphoma (ATLL), 5 peripheral T-cell lymphoma, NOS (PTCL-NOS), 5 T-cell large granular lymphocytic leukemia (T-LGL), and 6 T-cell prolymphocytic leukemia (T-PLL). The expression levels of PD-1 of lymphoma cells of the patients with MF/SS were widely variable (mean fluorescence intensity (MFI); Mean 949.0; range 101.0 - 3188.6) (Fig 1). 32.4% (11/34) of MF/SS cases showed high PD-1 expression equivalent to that of AITL cases. T-cell subset analysis to assess cell-of-origin was performed in 14 patients, including 4 patients with MF and 10 patients with SS (Table 1). While routine flow cytometric analysis showed similar immunophenotype other than the variation of PD-1, by flow cytometric T-cell subset analysis, we identified 3 patients with lymphoma cells showing T follicular helper (TFH) immunophenotype with CCR4+/CXCR3-/CCR6- and bright CD279 expression (case 2, 6, 8) (Table 2). Lymphoma cells of 8 patients showed effector memory CD4+ T-cell immunophenotype defined as CCR7-/CD45RA- (case 1, 3, 4, 5, 9, 10, 12, 13). Among these 8 patients, 2 patients had a subset of lymphoma cells showing central memory CD4+ T-cell immunophenotype defined as CCR7+/CD45RA- (case 5 and 12), and 2 patients had a subset with effector CD4+ cell immunophenotype defined as CCR7-/CD45RA+ (case 9, 13). 2 patients (case 7, 14) showed central memory CD4+ T-cell immunophenotype only, and 1 patient showed effector CD4+ T-cell immunophenotype only (case 11) (Table 2, Fig 2, 3). No cases showed Treg immunophenotype. The small sample size limited any subset analysis but we did not see obvious association between cell-of-origin of lymphoma cells and clinical features including prognosis, nodal presentation, number of circulating tumor cells, and histological findings in this study with limited number of cases.Conclusions: Lymphoma cells in MF/SS show marked heterogeneity of expression of PD-1 including clear subset arising from TFH. This suggests MF/SS may represent multiple biological entities. Further studies will be necessary to investigate the clinical significance of cell-of-origin of MF/SS. [Display omitted] DisclosuresYabe:Y-mAbs Therapeutics: Consultancy. Moskowitz:ADC Therapeutics: Research Funding; Incyte: Research Funding; Bristol Myers-Squibb: Consultancy, Research Funding; Takeda: Honoraria; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Horwitz:Infinity/Verastem: Consultancy, Research Funding; Trillium: Consultancy; Innate Pharma: Consultancy; Portola: Consultancy; Kyowa-Hakka-Kirin: Consultancy, Research Funding; Aileron Therapeutics: Consultancy, Research Funding; ADC Therapeutics: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Mundipharma: Consultancy; Millennium/Takeda: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Spectrum: Research Funding; Corvus: Consultancy.

Response at Interim Evaluation Predicts Survival after Autologous Stem Cell Transplantation in Nodal Peripheral T-Cell Lymphoma; A Nordic Lymphoma Group Study

Introduction: In the Nordic Lymphoma Group trial NLG T-01, patients with newly diagnosed peripheral T-cell Lymphoma (PTCL) were treated with six courses of CHOEP (up to 60 yrs) or CHOP (61-67 yrs) followed by high-dose chemotherapy (BEAM) and autologous stem cell transplantation (ASCT). At 5 years median follow-up, the progression-free survival of the trial cohort was 44%. On this background, the NLG-T01 treatment strategy has become the recommended first-line treatment for younger fit patients in the Nordic countries and in the latest ESMO guidelines for PTCL. Despite this intensive approach with up-front ASCT a fraction of patients still relapses. In an attempt to find factors predictive for survival after up-front ASCT we aimed to analyze the impact of radiologic response at the first interim evaluation on long-term survival.Methods: All NLG T-01 patients (TrialP) with "nodal" PTCL, i.e. anaplastic large cell lymphoma, ALK-negative (ALCL), angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma not otherwise specified (PTCL NOS), that actually received the planned ASCT were included. Using national (Sweden and Denmark) or site-specific (Finland and Norway) registries, additional patients (RegP) who received the same treatment schedule, but off-protocol, were identified, and data for these patients was collected retrospectively. Overall survival (OS) was calculated from date of stem cell reinfusion until death from any cause. The first interim computed tomography (iCT) scan was performed after 3 cycles of chemotherapy. Response assessment in the NLG-T-01 trial was based on the 1999 International Working Group criteria for response, which allowed for complete remission unconfirmed and these patients have been grouped with CR in the present analysis. Progressive Disease (PD) was defined as increase of ≥25% of any lesion.Results: Altogether, 132 patients were included in the present study (TrialP n= 92; RegP n=40). The clinical characteristics are presented in the Table. The 5-year OS among all the patients was 58%. Response at iCT was CR, partial remission (PR) and SD in 44%, 53% and 3% respectively. Of the four patients with SD at iCT, all four patients attained PR after completing six cycles of chemotherapy prior to ASCT. Kaplan-Meier estimates for OS are illustrated in the Figure and the 5-year OS was identical, 61%, for patients in CR and PR but 0%for patients with SD. Using log-rank comparisons patients achieving SD at iCT had a significantly worse survival compared to patients with CR or PR (p=.01).Discussion: This study is to our knowledge the first to analyze whether interim treatment response can predict long-term OS in "nodal" PTCL patients treated with CHOEP or CHOP consolidated by up-front ASCT. Patients with SD after three cycles of chemotherapy had a very poor survival compared to patients with PR or CR. This was an expected finding, and it confirms the importance of chemo-sensitive disease as a necessary pre-requisite in order to benefit from up-front high-dose consolidation. Using CT, there was no survival difference between patients with CR or PR at the first interim evaluation. A larger cohort might reveal further differences in subgroups, particularly if PET/CT based remission evaluation should confirm itself as a useful tool also in nodal PTCL. At present our study indicates that failure to achieve PR after three cycles of CHOEP/CHOP identifies patients at high risk of relapse/progression that are in need of a different therapeutic strategy than continuing with CHOEP/CHOP towards an ASCT. [Display omitted] [Display omitted] DisclosuresMannisto:Gilead: Other: Travel expenses; Celgene: Other: Travel expenses; Novartis: Other: Travel expenses; Amgen: Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses; Roche: Honoraria, Other: Travel expenses; Pfizer: Honoraria; SOBI: Honoraria.

Central nervous system involvement in T-cell lymphoma: A single center experience

Background We characterized the incidence of central nervous system (CNS) involvement, risk factors and outcome in a large single institution dataset of peripheral T-cell lymphoma (PTCL).Methods Retrospective review of the PTCL database at Memorial Sloan Kettering Cancer Center. We identified 231 patients with any subtype of PTCL between 1994–2011 with a minimum six months of follow-up or an event defined as relapse or death.Results Histologies included peripheral T-cell lymphoma–not otherwise specified (PTCL–NOS) (31.6%), angioimmunoblastic (16.9%), anaplastic large cell lymphoma (ALCL), ALK- (12.1%), ALCL, ALK + (6.1%), extranodal NK/T-cell lymphoma (7.4%), adult T-cell leukemia/lymphoma (ATLL) (7.4%), and transformed mycosis fungoides (8.7%). Seventeen patients had CNS disease (7%). Fifteen had CNS involvement with PTCL and two had diffuse large B-cell lymphoma and glioblastoma. Median time to CNS involvement was 3.44 months (0.16–103.1). CNS prophylaxis was given to 24 patients (primarily intrathecal methotrexate). Rates of CNS involvement were not different in patients who received prophylaxis. Univariate analysis identified stage III–IV, bone marrow involvement, >1 extranodal site and ATLL as risk factors for CNS disease. On multivariate analysis, >1 extranodal site and international prognostic index (IPI) ≥ 3 were predictive for CNS involvement. The median survival of patients with CNS involvement was 2.63 months (0.10–75).Conclusions Despite high relapse rates, PTCL, except ATLL, carries a low risk of CNS involvement. Prognosis with CNS involvement is poor and risk factors include: >1 extra nodal site and IPI ≥3.

Frontline Treatment of CD30+ Peripheral T-Cell Lymphomas with Brentuximab Vedotin in Combination with CHP: 3-Year Durability and Survival Follow-up

Frontline Treatment of CD30+ Peripheral T-Cell Lymphomas with Brentuximab Vedotin in Combination with CHP: 3-Year Durability and Survival Follow-up

B and T-Cell Lymphoma Patient-Derived Xenografts Recapitulate Aspects of Disease Biology and Progression and Represent Novel Tools for Preclinical Drug Development

Lymphomas represent nearly 70 distinct diseases with unique clinical presentations, therapeutic responses and underlying biology. There is a pressing shortage of publically available cell line and in vivo models of nearly all of these diseases, which has severely hampered efforts to understand and target their biology. To address this issue, we have established a repository of patient-derived xenografts (PDX) of lymphomas by engrafting human tumors into immunodeficient NOD/SCID/IL2rgnull (NSG) mice. These lymphomas, along with a spectrum of other PDXs of hematologic malignancies, are available to collaborators through the online portal PRoXe (Public Repository of Xenografts) at http://PRoXe.org. Blood and bone marrow specimens involved with tumor are injected by tail vein (IV) injection. Lymph node and extranodal biopsy specimens are implanted under the renal capsule as a 1x1x2mm tumor seed (renal), which maintains the in situ microarchitecture. A full description of xenografted lymphomas is included in the Table. Table 1DiseaseType of implant# in 1st passage# in 2nd passage or higherT-cell prolymphocytic leukemiaIV1Angioimmunoblastic T-cell lymphomaIV11Mantle cell lymphomaIV12Double-hit DLBCLIV2Sézary SyndromeIV1Adult T-cell Leukemia/LymphomaIV1Diffuse large B cell lymphomaIV2Diffuse large B cell lymphomarenal2Marginal zone lymphomarenal11NK/T-cell lymphomarenal1Peripheral T-cell lymphoma-NOSrenal1Breast implant-associated anaplastic large cell lymphomarenal1Engrafted PDXs have been extensively characterized by immunohistochemistry, flow cytometry, transcriptome sequencing and targeted DNA sequencing. Flow cytometric analysis of patient tumors and their respective xenografts consistently revealed highly concordant immunophenotypes compared to the original tumors. Similarly, immunohistochemistry of involved tissues confirmed retention of tumor immunophenotypes, architecture, and even tissue tropism in the PDXs. Examples include a Sézary syndrome PDX that was injected by tail vein and trafficked to spleen, bone marrow, blood and skin, a diffuse large B-cell lymphoma (DLBCL) PDX that infiltrated the CNS, and a second DLBCL PDX that was implanted into the renal capsule of the left kidney and progressed within 8 weeks to bilateral renal involvement. Other notable models include a breast implant-associated, ALK-negative anaplastic large cell lymphoma implanted under the renal capsule that metastasized to the liver and spleen while uniformly retaining CD30 positivity. Two double-hit lymphoma (DHL) PDXs maintained their CD20-negative phenotype through serial passage to P1. A peripheral T-cell lymphoma-NOS (PTCL) specimen implanted under the renal capsule engrafted in the spleen, with a notable admixture of nonmalignant T cells and scattered EBV-positive B cells. T-cell receptor gene rearrangement PCR performed on this PTCL demonstrated an identical rearrangement pattern in the primary tumor and the PDX. Luciferized mantle cell lymphoma and DHL PDXs clearly home to bone marrow, lymph nodes, spleen, and liver as early as two weeks after injection. These findings support the utility of these PDX lines as in vivo models that more accurately recapitulate the human disease than commonly used subcutaneous cell line models. In addition to generating PDXs that remain faithful to their source tumors, we have witnessed interesting examples of in vivo histologic transformation, opening the door to studies of disease progression. One primary follicular lymphoma specimen injected into a cohort of mice transformed to DLBCL in one mouse and a lymphoblastic lymphoma-like disease in another mouse, as confirmed by IHC and flow cytometry. Further xenografting of primary tumors is underway with the goal of establishing a large repository of lymphoma PDXs useful for biologic interrogation and preclinical trials. DisclosuresDavids:Genentech: Other: ad board; Pharmacyclics: Consultancy; Janssen: Consultancy. Shipp:Gilead: Consultancy; Sanofi: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Membership on an entity's Board of Directors or advisory committees.

Genomic signatures in T-cell lymphoma: How can these improve precision in diagnosis and inform prognosis?

The novel genetic information gained from genome-wide high throughput techniques has greatly improved our understanding of peripheral T-cell lymphoma (PTCL). PTCL consists of numerous distinct entities and is currently diagnosed using a combination of clinical and morphologic features and immunophenotyping together with limited molecular assays leading to an often fragmented, complicated diagnostic system. The diagnosis of many cases is challenging even for expert hematopathologists and more than a third of the cases cannot be further classified and thus put into the PTCL–NOS category. Gene expression profiling (GEP) has significantly improved the molecular classification of PTCLs and identified robust molecular signatures for common nodal subtypes of PTCL including angioimmunoblastic T-cell lymphoma (AITL), anaplastic T-cell lymphoma (ALCL), adult T-cell leukemia/lymphoma (ATLL) and extra-nodal NK/T cell lymphoma (ENKTL). These studies also led to identification of novel molecular subtypes with distinct prognosis, that otherwise could not be identified by conventional methods. Integration of massive sequencing strategies and gene expression has characterized driver genetic alterations in common subtypes like AITL, ALCL, ENKTL and other PTCLs. These studies have identified oncogenic pathways and genes affected in specific disease subtypes that can be potentially targeted by specific therapies. Novel treatment options with FDA approved drugs directed towards mutant IDH2, the NF-κB, JAK/STAT, or mTOR pathways illustrate the usefulness of genome-wide techniques to identify targets for therapy. In this review, we highlight recent advances in the molecular diagnosis and prognosis of PTCL using these genome-wide techniques.

Utility of interim and end-of-treatment PET/CT in peripheral T-cell lymphomas: A review of 124 patients.

According to the updated guidelines for imaging in lymphoma, 18F-FDG positron emission tomography/computed tomography (PET/CT) is recommended for staging and evaluation of treatment response in FDG-avid lymphomas. The purpose of the study was to evaluate the utility of PET/CT in nodal peripheral T-cell lymphomas (PTCL). Patients with newly diagnosed nodal PTCL (peripheral T-cell lymphoma NOS, anaplastic large-cell lymphoma, or angioimmunoblastic T-cell lymphoma) seen at five Danish hematology centers during the period 2006 to 2012 were included, if they had been pretherapeutically staged with PET/CT. Medical records were reviewed for baseline clinical and follow-up information. Staging, interim (I-PET), and end-of-treatment PET/CT (E-PET) studies were centrally reviewed, and reported using the Deauville 5-point score (DS). A total of 124 patients fulfilled the inclusion criteria. The median age was 58 years, and 88% received CHOP/CHOP-like therapy. Five years PFS and OS of the study population was 36.8% (95% CI 27.3-46.4) and 49.7% (95% CI 38.9-59.6), respectively. The presence of PET/CT-ascertained lung and/or liver involvement was associated with a worse outcome. The sensitivity of PET/CT for detecting biopsy-defined bone marrow involvement was only 18% (95% CI 4-43). An interim DS >3 was not prognostic for worse OS and PFS among CHOP/CHOP-like treated patients in uni- or multivariate analyses. A DS >3 after treatment predicted a worse prognosis. In conclusion, I-PET was not predictive of outcome in CHOP/CHOP-like treated PTCL patients when using the DS. Prospective studies are needed to determine the optimal use of PET/CT in PTCL including the role of quantitative PET/CT analysis.

Primary Cutaneous Peripheral T-Cell Lymphoma Not Otherwise Specified: A Rapidly Progressive Variant of Cutaneous T-Cell Lymphoma.

Primary Cutaneous Peripheral T-Cell Lymphoma NOS (PTL-NOS) is a rare, progressive, fatal dermatologic disease that presents with features similar to many common benign plaque-like skin conditions, making recognition of its distinguishing features critical for early diagnosis and treatment (Bolognia et al., 2008). A 78-year-old woman presented to ambulatory care with a single 5 cm nodule on her shoulder that had developed rapidly over 1-2 weeks. Examination was suspicious for malignancy and a biopsy was performed. Biopsy results demonstrated CD4 positivity, consistent with Mycosis Fungoides with coexpression of CD5, CD47, and CD7. Within three months her cancer had progressed into diffuse lesions spanning her entire body. As rapid progression is usually uncharacteristic of Mycosis Fungoides, her diagnosis was amended to PTL-NOS. Cutaneous T-Cell Lymphoma (CTCL) should be suspected in patients with patches, plaques, erythroderma, or papules that persist or multiply despite conservative treatment. Singular biopsies are often nondiagnostic, requiring a high degree of suspicion if there is deviation from the anticipated clinical course. Multiple biopsies are often necessary to make the diagnosis. Physicians caring for patients with rapidly progressive, nonspecific dermatoses with features described above should keep more uncommon forms of CTCL in mind and refer for early biopsy.

Patterns of Central Nervous System Relapse in Peripheral T-Cell Lymphomas – Population-Based Data from the Swedish Lymphoma Registry

IntroductionDisease relapse involving the central nervous system (CNS) carries a dismal prognosis in patients with aggressive lymphoma. Risk factors for CNS-relapse have included involvement of lymphoma at specific anatomical sites, proliferation rate and high tumor burden. The risk and importance of CNS-relapse in peripheral T-cell lymphomas (PTCL) has been very little studied. So far, the only study focusing on CNS-relapse in PTCL found elevated LDH and paranasal sinus involvement to be independent risk factors and that CNS-relapse was associated with an inferior survival. Recently, several studies have highlighted the dismal prognosis of relapsed PTCL in general. In this study we aimed at analyzing risk factors for CNS involvement in first relapse and the outcome of these patients, in a large population-based cohort of PTCL patients.Materials and methodsThrough the Swedish Lymphoma Registry we identified all adult (>18 years) patients diagnosed with PTCL between January 1st 2000 and December 31st 2009. Primary cutaneous, primary leukemic types and T-cell lymphoblastic lymphoma were excluded. Information on first relapse was collected from patient files retrospectively after informed consent.ResultsOut of 755 patients identified through the registry, 10 patients had CNS involvement at diagnosis and were excluded from further analyses. Data on first relapse was available for 618, and among these 369 patients experienced relapse or progression. Thirty-one patients (5.0 %) experienced progression or relapse involving the CNS after a median time of 4.3 months (range 1.1-45 months) from diagnosis. Thirteen patients experienced an isolated CNS relapse/progression and 18 as part of a systemic relapse. Sixteen patients relapsed after responding to primary therapy (10 CR, 6 PR), and 15 patients with refractory disease had CNS-progression (1 SD, 14 PD). Histologic subtypes among the 31 patients were ALK-positive anaplastic large cell lymphoma (ALCL) (n=3), ALK-negative ALCL (n=3), ALK-unknown ALCL (n=1), angioimmunoblastic T-cell lymphoma (n=3), peripheral T-cell lymphoma NOS (n=13), enteropathy-associated T-cell lymphoma (n=3), NK/T-cell lymphoma nasal type (n=1), hepatosplenic T-cell lymphoma (n=1) and unclassified T-cell lymphoma (n=1). All 31 patients had received chemotherapy with curative intent and 6 received intrathecal prophylaxis. In multivariable analysis, the presence of B-symptoms (HR 2.79 95% CI 1.14-6.82, p=0.024), >1 extranodal site of disease (HR 3.28[1.41-7.64], p=0.006) and skin involvement (HR 3.06 [1.10-8.49], p=0.032) were independent risk factors for CNS relapse.Median survival for patients with CNS involvement at relapse or progression was 3.3 months (range 0-124) compared to 3.7 (range 0-129) for patients without CNS involvement and CNS involvement was not a risk factor for OS after relapse/progression (HR 1.08 [0.73-1.59], p=0.700).For relapsing patients only age was predictive of inferior survival (1.014 [1.002-1.027], p=0.026) whereas in patients with primary refractory disease, male gender predicted inferior survival (2.93 [1.54-5.58], p=0.001) and angioimmunoblastic T-cell lymphoma was associated with better survival (0.41 [0.18-0.95], p=0.037).ConclusionsCNS involvement, isolated or as part of a systemic first relapse, occurred in 5% of the patients in our series, which is similar to the incidence in larger series dominated by B-cell lymphomas. In our cohort, B-symptoms, >1 extranodal site of disease and skin involvement were independent predictors for CNS-relapse. The outcome of relapsed patients was very poor in general, and CNS-involvement did not convey worse outcome compared to patients with systemic relapse only. With current treatment strategies the uncommon CNS-relapses seem to be a problem of lower magnitude compared to the frequent systemic relapses. Future improvements in the treatment of PTCLs could possibly increase the importance of identifying patients at risk for CNS-relapse, and our study provides data on this poorly described complication. DisclosuresNo relevant conflicts of interest to declare.

Brentuximab Vedotin in Combination with Chp in Patients (Pts) with Newly-Diagnosed Cd30+ Peripheral T-Cell Lymphomas (Ptcl): 2-Year Follow-Up

ABSTRACT Aim: PTCL comprises a subset of aggressive non-Hodgkin lymphomas. Outcomes of frontline treatment (tx) are poor, with complete remission (CR) rates of 39–53% (Reimer 2009; D'Amore 2012) and 5-yr overall survival (OS) rates of 12–49%, depending on subtype (Vose 2008). Brentuximab vedotin (ADCETRIS®; BV) has shown clinical activity in a phase 1 trial of BV in sequence with CHOP or in combination with CHP (CHOP without vincristine; A + CHP) in pts with newly-diagnosed PTCL (Fanale, ASH 2013). Methods: This phase 1, open-label study assessed the safety and efficacy of BV administered sequentially with standard-dose CHOP or in combination with CHP for the frontline tx of PTCL (ClinicalTrials.gov NCT01309789). ALK+ systemic anaplastic large cell lymphoma (sALCL) pts must have had IPI score ≥2. Combination tx included a cohort to determine the recommended dose of BV in A + CHP to be evaluated in an expansion cohort (6 cycles q3wk). Responders could receive single-agent BV (1.8 mg/kg q3wk) for up to 10 additional cycles. Updated progression-free survival (PFS) and OS data from combination tx is presented. Results: The median age of pts was 56 yrs (range, 21–82; n=26). Diagnoses included sALCL (n = 19; 16 ALK-), peripheral T-cell lymphoma-NOS (n = 2), angioimmunoblastic T-cell lymphoma (n = 2), adult T-cell leukemia/lymphoma (n = 2), and enteropathy-associated T-cell lymphoma (n = 1). The maximum tolerated dose of BV in A + CHP was not exceeded at 1.8 mg/kg IV, based on 1 DLT (Grade 3 rash). 23 of 26 pts completed 6 cycles of A + CHP. Treatment-emergent adverse events (≥40%) included peripheral sensory neuropathy, nausea, fatigue, alopecia, diarrhea, and dyspnea. At the end of combination tx, the objective response rate was 100% and CR rate was 88%. After a median observation time of 27.1 months, the 2-yr PFS and OS rates were 54% (95% CI 32, 71) and 80% (95% CI 59, 91), respectively. The estimated median PFS was not reached. No pts went on to receive a consolidative stem cell transplant. Conclusions: A + CHP delivered durable remissions in newly-diagnosed PTCL pts, with a 2-yr PFS rate of 54%. A phase 3 study comparing A + CHP to CHOP in the frontline tx of PTCL is underway (ClinicalTrials.gov NCT01777152). Disclosure: M.A. Fanale: Acted as a consultant for: Seattle Genetics, Inc. Honoraria provided by: Seattle Genetics, Inc. Travel expenses provided by: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc.; S.M. Horwitz: Consultant: Celgene, Seattle Genetics, Inc., Janssen, Takeda International Pharmaceuticals International Co. Research funding/grants: Takeda International Pharmaceuticals International Co., Kiowa Kirin, Allos, Celgene, Infinity, Seattle Genetics, Inc.; A. Forero-Torres: Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Speakers bureau: Seattle Genetics, Inc.; N.L. Bartlett: Acted as a consultant for: Seattle Genetics, Inc. Travel expenses provided by: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc.; R.H. Advani: Research funding/grants: Seattle Genetics, Inc., Genentech, Takeda Pharmaceuticals International Co., Abbott, Allos, Janssen, Pharmacyclics Consultant: Seattle Genetics, Inc., Genentech, Takeda Pharmaceuticals International Co., Celgene; B. Pro: Acted as a consultant for: Seattle Genetics, Inc. Travel expenses provided by:Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc.; R.W. Chen: Acted as a consultant for:Seattle Genetics, Inc. Travel expenses provided by:Seattle Genetics, Inc. Research funding/grants provided to the authors institution by:Seattle Genetics, Inc. Speakers bureau: Seattle Genetics, Inc.; A. Davies: Acted as a consultant for: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Honoraria provided by: Takeda Pharmaceuticals International Co.; T. Illidge: Acted as a consultant for: Seattle Genetics, Inc. Takeda Pharmaceuticals International Co. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Honoraria provided by: Takeda Pharmaceuticals International Co.; D. Huebner: Employment: Takeda Pharmaceuticals International Co. Equity ownership (including stock options): Takeda Pharmaceuticals International Co.; D.A. Kennedy: Employment: Seattle Genetics, Inc. Equity ownership (including stock options): Seattle Genetics, Inc.; A.R. Shustov: Acted as a consultant for: Seattle Genetics, Inc. Research funding/grants provided to the authors institution by: Seattle Genetics, Inc. Honoraria provided by: Seattle Genetics, Inc. Speakers bureau: Seattle Genetics, Inc.

The International Prognostic Index Predicts Outcome In Patients With Untreated Nodal Peripheral T-Cell Lymphomas Staged With PET/CT

BackgroundPET/CT has proven to be highly accurate for staging of Hodgkin lymphoma. A recent study also reported that PET/CT detected additional disease sites in 50% of patients with peripheral T-cell lymphoma (PTCL) as compared to conventional CT-based staging and had higher sensitivity for extranodal disease. This may challenge the validity of pre-therapeutic prognostic tools such as the widely used international prognostic index (IPI), which contains imaging-depended clinical features such as Ann Arbor stage and extranodal disease. AimTo examine the validity of IPI in PET/CT staged PTCL patients treated with CHOP or CHOP-like first line therapies. Patients and MethodsThe present retrospective study included PTCL patients from five Danish referral hematology centers. Potential candidates for the study were identified from a search in the Danish Lymphoma Registry (LYFO). Patients with PTCL not otherwise specified (PTCL NOS), anaplastic large cell lymphoma (ALCL), or angioimmunoblastic T-cell lymphoma (AITL) were included if they underwent PET/CT staging and were treated with CHOP or CHOP-like first-line therapy +/- consolidating high-dose therapy. Medical records were retrieved and reviewed for all included patients. ResultsDuring the time period 2006-2013 a total of 137 out of 259 PTCL patients were staged with PET/CT. Of these 119 (87%) received CHOP or CHOP-lile first-line therapy and were included in this analysis. The patients were diagnosed with PTCL NOS (n=49), AITL (n=18), and ALCL (n=52). The median age was 58 yrs. and the male:female ratio was 1.3. Advanced stage disease (III-IV) was diagnosed in 71% (n=85) and 27% (n=32) of the patients had more than one extranodal site involved. In univariate Cox regression analyses elevated LDH (HR 2.77, 95%CI 1.44-5.34), > 1 extranodal disease site (HR 3.09, 95%CI 1.67-5.72), age > 60 yrs. (HR 2.49, 95%CI 1.35-4.59), ECOG performance > 1 (HR 2.03, 95% CI 1.08-3.83), and Ann Arbor stage III-IV (HR 2.43 95%CI 1.08-5.73) were all significantly associated with inferior overall survival (OS). The presence of more than one extranodal disease site was an adverse prognostic factor for both age groups. In a multivariate Cox regression analysis including these variables, age > 60 yrs., > 1 extranodal site, and elevated LDH retained independent association with short OS. Using IPI score 0-1 (low-risk) as reference group score the HRs for death were 2.49 (95%CI 0.87-7.19) for low-intermediate, 4.31 (95%CI 1.53-12.09) for high-intermediate, and 12.74 (95%CI 4.43-36.61) for high risk patients. IPI-specific OS fractions are show in the figure. ConclusionsDespite the potential stage migration associated with the introduction of new and more accurate imaging modalities such as PET/CT, the original IPI developed two decades ago continues to be a highly valid tool for predicting overall survival in PTCL patients treated with CHOP or CHOP-like first-line therapies. [Display omitted] TCEG, MBP, and LCG contributed equally to the present work. Disclosures:No relevant conflicts of interest to declare.

Non-Hodgkin's Lymphomas Associated With Positive Hepatitis-C Virus Infection: A Prospective Multicentric Observational Study On Behalf Of The “Rete Ematologica Lombarda/Hematology Network Of Lombardia Region”

IntroductionThe association between hepatitis-C virus (HCV) infection and non-Hodgkin's lymphomas (NHL) has been demonstrated in epidemiological studies. In Lombardia, a densely populated region of northern Italy with around 10 millions of inhabitants, the prevalence of infected people is around 5%. In 2008, the “Rete Ematologica Lombarda” (Hematology Network of Lombardia region) started a prospective multicentric observational study, with the aim to collect data on virological and hematological features, on treatment and outcome of HCV-related NHL. Herein, we present the final results of this study. MethodsBetween January 2008 and December 2012, 241 consecutive adult patients (pts) with first diagnosis of NHL associated with HCV-positivity were enrolled in this prospective observational study (“Registro Lombardo dei Linfomi HCV-positivi”), approved by the Regional Administration and by IRBs of 10 Hematology Centres of Lombardia region. All pts signed a written informed consent. HIV-positive pts were excluded. ResultsMedian age at lymphoma diagnosis was 69 years (yrs) (range 32-90); females were 60%. Histotypes were classified as follows: diffuse large B-cell lymphoma (DLBCL) (44%), marginal zone lymphoma (MZL) (28%), follicular lymphoma (10%), low-grade B-cell lymphoma NOS (10%), small lymphocytic lymphoma (SLL) (3%), lymphoplasmacytic lymphoma (3%), mantle cell lymphoma (1%), peripheral T-cell lymphoma NOS (1%). Ann Arbor stage was III-IV in 79% of pts, with bone marrow involvement in 47%. ECOG score was ≥ 2 in 16% of pts; 63% of pts showed at least one extranodal localization (spleen in 22%, skin in 11%, liver in 10%, Waldeyer's ring in 5%, ocular adnexa in 3%). Virological features and treatment details are summarized in Table 1. HCV-positivity was detected before the diagnosis of NHL in 166 pts (69%) and median time between HCV detection and NHL diagnosis was 11 yrs. Serum monoclonal component (p=0.003), autoimmunity manifestations (p<0.001) and cryoglobulinemia (p=0.002) resulted more frequent in indolent NHL respect to aggressive subtypes. A shorter overall survival (OS) was observed in pts with ECOG ≥ 2 (p<0.001), hemoglobin < 12 g/dl (p=0.008), albumin < 3.5 g/dl (p=0.005), platelets < 100 x 109/L (p<0.001) and lactate dehydrogenase ≥ UNL (p=0.031). Data on first line treatment for NHL were available in 231 pts: 178 pts (77%) received chemotherapy (CHT) [plus Rituximab (R) in 122]; anthracycline contain-regimens (+/- R) were used in 121 pts (52%). Forty pts (17%) developed liver toxicity of any grade (grade III-IV in 19 pts) and 22 pts (10%) interrupted early the treatment. Fifty-three pts were treated with antiviral therapy (AT) for active HCV infection and among them 12 pts (8 MZL, 3 low-grade B-cell lymphoma NOS, 1 SLL) were treated with AT as first anti-lymphoma therapy; 8 pts obtained a virological response and a complete lymphoma response, 2 pts had a partial response (HCV-RNA negative in 1), 1 pt had neither hematological nor virological response and 1 pt is still on therapy. After a median follow-up of 32 months, 47 pts (20%) died (24 with aggressive NHL, 23 with indolent NHL): 23 due to lymphoma, 10 due to cirrhosis/hepatocarcinoma, 7 due to other solid neoplasms, 7 due to other causes. ConclusionsIn this prospective study conducted in Lombardia, a northern region of Italy, the most common histologies of HCV-associated NHL are DLBCL and MZL. In nearly 70% of pts, first detection of HCV positivity preceded the lymphoma diagnosis. A proportion of pts developed meaningful liver toxicity and/or were not able to complete the therapeutic program. In the indolent lymphomas treated with AT as first anti-lymphoma approach, virological and hematological responses are achieved in about two thirds of pts. Disclosures:No relevant conflicts of interest to declare.

Brentuximab Vedotin Administered Before, During, and After Multi-Agent Chemotherapy In Patients (pts) With Newly-Diagnosed CD30+ Mature T- and NK-Cell Lymphomas

Brentuximab Vedotin Administered Before, During, and After Multi-Agent Chemotherapy In Patients (pts) With Newly-Diagnosed CD30+ Mature T- and NK-Cell Lymphomas

Prolonged Survival in Secondary CNS Lymphoma Following High Dose Thiotepa/Busulfan-Based Chemotherapy (HDTB) and Autologous Stem Cell Transplantation (ASCT): Single Institution Results From Calgary, Canada

Abstract 2003Secondary CNS Lymphoma (SCNSL) is relatively rare, but associated with median survival of less than 4 months following conventional therapies. In an effort to improve upon these poor results, the Calgary ASCT Program has offered HDTB/ASCT to referred SCNSL patients who have good performance status, adequate organ function, and chemosensitive disease. The purpose of this study was to retrospectively review outcomes of these pts. In total, 14 pts aged 40–67 years (median 58) with SCNSL were transplanted in Calgary from 1997–2012 (9 pts from 2010–2012). Twelve pts experienced CNS progression after completing (n=9) or while still receiving (n=3) initial systemic therapy. The median time to progression (TTP) from initiation of systemic therapy was 6 months (mo, range 1– 132) for these 12 pts. Only one patient had received CNS prophylaxis with intrathecal chemotherapy. In addition to these 12 pts, 2 pts had SCNSL coincidental with initial diagnosis of systemic lymphoma. Histology included diffuse-large B-cell lymphoma in 12 pts (including one intravascular lymphoma and two transformed from prior indolent lymphoma), plasmablastic in 1 pt, and peripheral T-cell lymphoma NOS in 1 pt. Sites of CNS involvement included: brain=6,meninges=5, brain+meninges=1, meninges+eye=1, intramedullary spinal cord=1. High risk features for CNS relapse of initial systemic lymphoma presentation (N=12) included elevated LDH (n=7/10), extranodal disease (END, n=12/12), >1 site END (n=6/12), ECOG 2–4 (n=5/10), IPI 3–5 (n=7/10). At the time of HDTB/ASCT, 7 pts had isolated CNS disease and 7 pts had CNS and systemic lymphoma. Pre-ASCT CNS directed therapy included intrathecal (IT) methotrexate (MTX) alone (n=1), IT MTX plus whole brain radiotherapy (n=1), IT MTX plus high dose intravenous MTX (n=1), high dose MTX plus cytarabine or DHAP (n=10), R-HyperCVAD (n=1). Disease status at HDTB/ASCT was complete response (n=1), partial response (n=13). Prior to 2011 (n=7) high dose therapy involved: thiotepa 300mg/m2.IV days -8 and -7, busulfan 3.2 mg/kg IV daily on days -6, -5, -4, and cyclophosphamide 2 g/m2.IV days -3 and -2, followed by ASCT on day 0 (TBC). After 2011 (n=7), high dose therapy involved: rituximab 375 mg/m2 day -7, thiotepa 250 mg/m2 day -6,-5, busulfan 3.2 mg/kg IV daily on days -4, -3, -2, melphalan 100mg/m2IV on day -1, followed by ASCT on day 0 (RTBM). At a median follow-up of 15 months (range 2–89), projected 2-year PFS is 61% and OS 68%. One pt died of treatment-related encephalopathy and pneumonia 4mo post-ASCT, 3 pts died of relapsed systemic lymphoma 2–6mo after TBC/ASCT, 1 pt with plasmablastic lymphoma is currently alive but with relapsed disease 5mo post RTBM/ASCT, and 9 pts are alive and relapse free. The figure below illustrates a possible plateau on PFS and OS curves for the 14 treated pts. Conclusion:HDTB/ASCT offers a potentially curative approach in selected patients with SCNSL. [Display omitted] Disclosures:Off Label Use: In Canada, all the TBC and RTBM drugs are off label (ie no Health Canada NOC indication) for CNS lymphoma. Stewart:Honorarium for advisory board, Otsuka America Pharmaceutical, Inc. Rockville, Maryland: Honoraria.

Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy As Frontline Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell Lymphomas

Brentuximab Vedotin Administered Concurrently with Multi-Agent Chemotherapy As Frontline Treatment of ALCL and Other CD30-Positive Mature T-Cell and NK-Cell Lymphomas

Diagnostic Accuracy of a Defined Immunophenotypic and Molecular Genetic Approach for Peripheral T/NK-Cell Lymphomas: A North American PTCL Study Group Project

AbstractAbstract 1545 Introduction:The diagnosis of peripheral T-cell lymphoma (PTCL) is difficult and accurate diagnosis and subclassification relies on correlating histologic, immunophenotypic, molecular genetic, and clinical data. Evidence-based guidelines for the appropriate diagnostic work-up of PTCL are lacking. The objective of this study was to evaluate a large series of PTCLs by experienced hematopathologists with a tiered approach to immunohistochemistry (IHC) and molecular genetic characterization to document overall diagnostic accuracy and clinical relevance using this approach. Methods:7 experienced hematopathologists from 5 institutions reviewed 374 cases of peripheral T and NK cell lymphomas (referred to collectively as PTCL). 6 cases of cutaneous T-cell lymphoma were excluded after final review in addition to 29 non-PTCL cases submitted as control cases to mimic diagnostic practice during the review. Cases received tier 0, 1 and 2 diagnoses by 3 independent pathologists, based on review of hematoxylin and eosin (HE) stain with basic demographic data, panel 1 IHC (CD3, CD5, CD10, CD20, CD21, CD30, CD45, PAX5), and panel 2 IHC (CD2, CD4, CD7, CD8, CD23, PD1, CD56, EBER, ALK, TIA1, TCRg, TCRbF1), respectively. A tier 2b diagnosis was then rendered after gene rearrangement data were available. A final consensus diagnosis was rendered after discussion of each case by the 3 reviewers with all available clinical data. Overall survival (OS) was assessed using Kaplan-Meier (KM) curves and Cox proportional hazards models. Results:1122 individual diagnoses leading to 339 final consensus PTCL diagnoses were rendered. 341 (91%) cases had complete phenotypic data and 241 had gene rearrangement data. There was no bias of missing data according to final diagnosis subtype. Reviewer diagnoses using specific WHO subclassification were 16.3%, 36.9%, 82.7%, and 85.9% for tier 0, 1, 2, and 2b, demonstrating a significant increase in diagnostic certainty after a complete IHC panel. Gene rearrangement only contributed to a change in diagnosis in 51/650 (8%) individual reviews. Across all 374 cases, a small number of cases (n=28, 7.5%) showed no agreement among the 3 independent reviewers after tier 2b and required debate. These generally represented refinement of the subclassification of a PTCL. The most common disagreements were between PTCL, not otherwise specified (nos) vs. unclassifiable T-cell lymphoma, and PTCL, nos vs. angioimmunoblastic T-cell lymphoma (AITL). Currently, OS data was available in 198 cases and 52% have died (median age follow-up of 15 months for those still alive, range 0–160 mo). Figure 1 shows the KM survival curves for types with more than 10 cases. Of note, unclassifiable PTCL cases had poor OS, comparable to PTCL nos; a trend was seen for CD30+ ALK- ALCL to have a longer OS compared to PTCL nos (HR=0.5, 95% CI: 0.21–1.19, P=.09). EBER positivity in tumor cells was associated with poor OS in the cohort of all PTCL patients (HR=2.32, 95% CI: 1.28–4.23, p=0.006, Figure 2); the association was similar when nasal NK/T-cell lymphoma cases were excluded (HR=2.50, 95% CI: 1.00–6.26, p=0.05). Trends for poor prognosis were also seen for TIA-1 expression in PTCL, nos (HR=1.9, 95% CI 0.91–3.96, P=.09) and PD1 expression in AITL (HR=6.25, 95% CI 0.85–46.09, P=.07). Clinical data collection is still ongoing and will be updated. Conclusions:We demonstrate the diagnostic accuracy among experienced hematopathologists of a defined IHC panel, showing an overall ability to reach consensus diagnosis of 93% in PTCL cases. The resulting consensus diagnostic subtypes showed expected outcomes relative to other large series of PTCLs, and EBER positivity is a poor prognostic marker among T and NK cell lymphomas. A tiered approach to IHC is recommended when a PTCL is under differential diagnostic consideration since the first tier can often resolve the main question of whether a lesion is reactive or lymphoma. This can lead to more efficient use of the expanded tier 2 panel that will enable diagnosis and specific subclassification of PTCL. Gene rearrangement studies are not required in the great majority of cases. This evidence-based approach to the diagnosis of PTCL should inform practicing pathologists, clinical trial design, and policy makers regarding required ancillary studies in this group of diseases. [Display omitted] [Display omitted] Disclosures:Hsi:Allos: Research Funding. Said:Allos: Research Funding. Macon:Allos: Research Funding. Rodig:Allos: Research Funding. Gascoyne:Seattle Genetics: Research Funding. Ondrejka:Allos: Research Funding. Dorfman:Allos: Research Funding. Maurer:Allos: Research Funding. Dogan:Allos: Research Funding.

Efficacy of alemtuzumab (ALZ) in combination with dose-adjusted EPOCH (DA-EPOCH) in untreated nodal peripheral T-cell lymphoma (PTCL).

8051 Background: The survival of patients (pts) with PTCL (excluding ALCL) is disappointing following anthracycline-based therapy and novel approaches are needed. In diffuse large B-cell lymphoma, the addition of anti-CD20 therapy to CHOP has significantly improved outcome and we investigated if in PTCL, adding ALZ – which targets CD52, expressed on most PTCLs – was feasible and improved outcome. Methods: This was a single-center phase I/II trial of ALZ, in combination with DA-EPOCH in patients with treatment-naïve CD52+ PTCL. The MTD of 30 mg ALZ was combined with DA-EPOCH for phase II evaluation resulting in an intention-to-treat population (ITTP) of 30 pts. Results: Patient (n=30) characteristics: median (range) age 50 (17-77); M:F 1:1; Stage III/IV 27 (90%); IPI ≥2 22 (73%). Histologies: ATLL 11 (37%), PTCL NOS 6 (20%), AITL 5 (16%), Hepatosplenic 3 (10%), Peripheral T NK cell 2 (7%), Other 3 (10%). At 67 months median follow-up, 11 patients were alive, 10 disease-free. Median overall (OS) and event-free survivals (EFS) were 15.4 and 6.7 months respectively. Outcome was substantially better for pts with ‘nodal’ (AITL, PTCL-NOS, Other) compared to ‘non-nodal’ (ATLL and ‘extranodal’ histologies) PTCL subtypes. 3-year OS for the two groups was 58.3% and 27.8% respectively (p=0.082); 3-yrs EFS was 50% (median 27.0 months) and 22.2% (median: 5 months) respectively (p=0.041). Half of the ‘nodal’ PTCL pts had sustained long-term complete remissions demonstrated by a plateau in the EFS curve at 27 months. There were 3 treatment related deaths: 2 from neutropenic sepsis; 1 from toxoplasma. Other toxicities included CMV and BK virus reactivation in 53% and 30% respectively. Febrile neutropenia was seen in 20% and grade 4 thrombocytopenia in 12 % of cycles. Conclusions: Although it has significant infectious toxicity, ALZ 30mg and DA-EPOCHin untreated PTCL is feasible and associated with a long-term favorable outcome in nodal but not extranodal or leukemic PTCL. A phase III study of ALZ 30mg with anthracycline-based therapy is ongoing and we await the results with interest.

Brentuximab vedotin for relapsed or refractory non-Hodgkin lymphoma: Preliminary results from a phase II study.

8070 Background: Brentuximab vedotin is a CD30-directed antibody-drug conjugate approved for the treatment of Hodgkin lymphoma and systemic anaplastic large cell lymphoma (ALCL) after failure of other therapies. Based on the high objective response rate observed in patients with systemic ALCL, a type of non-Hodgkin lymphoma that is characterized by homogeneous CD30 expression, a study was initiated in other non-Hodgkin lymphomas that express the CD30 target. Methods: A phase 2 open-label single-arm study is underway in patients with relapsed or refractory CD30-positive non-Hodgkin lymphoma, excluding ALCL (NCT01421667). Brentuximab vedotin is administered IV at 1.8 mg/kg every 3 weeks until disease progression or unacceptable toxicity. The primary endpoint is objective response rate assessed by the Revised Response Criteria for Malignant Lymphoma (Cheson 2007). Tumor specimens are assessed by central lab in order to characterize the relationship of CD30 expression with antitumor activity. Results: Ten patients (age range 28–83; 5 M, 5 F) have enrolled to date. Diagnoses include diffuse large B-cell lymphoma (DLBCL, n=2), EBV-positive DLBCL of the elderly (n=3), primary mediastinal B-cell lymphoma (n=2), peripheral T-cell lymphoma NOS (n=2), and angioimmunoblastic T-cell lymphoma (AITL). Patients had received 1–6 prior chemotherapy regimens; 3 patients had prior stem cell transplants. Of 6 patients who have completed the cycle 2 response assessment, 2 attained complete remission, 1 with DLBCL (90% CD30+) and 1 with AITL (8% CD30+), 1 had stable disease, and 3 had progressive disease. Treatment-related serious adverse events observed to date were rash, febrile neutropenia, and mastoiditis. Conclusions: Preliminary results suggest that brentuximab vedotin may have antitumor activity in patients with relapsed or refractory CD30-expressing non-Hodgkin lymphomas, in addition to the efficacy previously observed in systemic ALCL. Updated study results will be presented.

Progression-free survival for subsequent relapses in patients with peripheral T-cell lymphoma (PTCL).

8063 Background: In B-cell lymphoma, overall response (ORR) is lower and progression free survival (PFS) is often shorter with each subsequent progression. However, this has not been described for PTCL. Methods: We undertook a retrospective analysis in two U.S. centers (MSKCC and UNMC) and in GELA studies. All data for PTCL were reviewed to collect data for each line of therapy: treatment, response, PFS, date of next treatment, and survival. When date of progression could not be defined we calculated PFS as the time to next treatment. Pts who did not progress, died during first line, or were untreated at progression 1 were excluded. Data were collected for 4 lines of treatment, front line and 3 progressions. Results: 254 pts were identified. 205 were analyzed (49 excluded for missing data): GELA 116, MSKCC 51, and UNMC 37. Diagnoses were PTCL NOS in 34% and 60%, AITL in 49% and 35%, ALCL Alk- in 3% and 5%, and others in 15% and 18% for GELA and US centers respectively. 67% were male, median age was 51 vs 58 y. Advanced stage was more frequent in GELA (79% vs. 56% for US); baseline IPI was ≥2 in 90% vs 71%. Multidrug regimens were given in 99% and 80% for front line, 67% and 66% for 2nd line, 61% and 50% for 3rd line, 53% and 54% for 4th line, for GELA and US. Significantly fewer pts received each subsequent line of therapy with 205 pts receiving 2nd line, 96 pts 3rd line and 38 pts 4th line. No pt ≥65 y received 4th line treatment. Responses and PFS are listed in the table. Conclusions: For pts with PTCL, similar to B-cell lymphomas, ORR and PFS decrease with each line of therapy. When evaluating the activity of therapies in relapsed PTCL, line of therapy is a consideration and this series provides a benchmark for comparison. Based on this dataset, it is possible that better responses will be seen as new agents are moved into earlier treatment paradigms. [Table: see text]

A large single-center experience with allogeneic stem-cell transplantation for peripheral T-cell non-Hodgkin lymphoma and advanced mycosis fungoides/Sezary syndrome

BackgroundThe prognosis for patients with most forms of T-cell lymphoma is poor. Allogeneic hematopoietic stem-cell transplantation (HSCT) may improve the outcome. Patients and methodsThis study examines the outcome of 52 patients who underwent ablative or nonablative allogeneic HSCT for peripheral T-cell lymphoma (PTCL) or advanced mycosis fungoides/Sezary syndrome over a 12-year period at a single institution. We divided the patients into those with predominantly nodal histologies: peripheral T-cell not otherwise specified (PTCL NOS), angioimmunoblastic (AITL), or anaplastic large cell lymphoma, T/null type (systemic) (ALCL), and predominantly extranodal histologies: natural killer (NK)/T cell, enteropathy type, hepatosplenic, subcutaneous panniculitic, mycosis fungoides, or T cell or NK cell other. ResultsMedian follow-up of survivors is 49 months. Non-relapse mortality and relapse at 3 years was 27% and 43%, respectively. The incidence of grade II–IV acute graft-versus-host disease (GVHD) was 21%. The incidence of extensive chronic GVHD at 2 years was 27%. The 3-year progression-free survival was 30%: 45% in patients with predominantly nodal histologies (PTCL NOS, AITL, and ALCL) and 6% in patients with predominantly extranodal histologies (P=0.016). Overall survival at 3 years was 41% for all patients. ConclusionAllogeneic HSCT can produce long-term remissions in relapsed/refractory T-cell lymphoma, especially those with nodal histologies.