Peripheral T-cell Lymphoma NOS Research Articles

Mitoxantrone Hydrochloride Liposome, Gemcitabine, Vinorelbine with or without Rituximab (GVM±R) in Patients with Relapsed or Refractory Aggressive Non-Hodgkin's Lymphoma

Background: In patients with relapsed/refractory (r/r) aggressive non-Hodgkin lymphoma (aNHL), achieving a response to salvage therapy is a crucial predictor for long-term survival, as only chemosensitive patients have the opportunity to undergo autologous stem cell transplantation. Mitoxantrone hydrochloride liposome (PLM60) has shown good efficacy and safety in r/r peripheral T-cell lymphoma (PTCL) based on a prior study, with an objective response rate (ORR) of 40.7% and a complete response rate (CRR) of 20.4% (2020 ASH abstract 42). To determine the appropriate dosage of PLM60 in a multi-drug combination chemotherapy, we conducted a phase I clinical study aiming to explore the maximum tolerated dose (MTD) of PLM60 when combined with gemcitabine, vinorelbine, with or without rituximab (GVM±R). This trial was registered at www.clinicaltrials.gov as NCT05299164. Methods: The study was a prospective, single-center, single-arm, 3+3 dose-escalation study involving patients aged 18-70 years with r/r aNHL. PLM60 was administered on day 1 at four different dose levels (DL) (DL1: 16 mg/m 2, DL2: 18 mg/m 2, DL3: 20 mg/m 2, DL4: 22 mg/m 2), gemcitabine on day 1 and 8 at 800 mg/m 2, vinorelbine on day 1 and 8 at 20 mg/m 2, and rituximab on day 0 at 375 mg/m 2 (only administered in CD20+ lymphoma based on the investigator's judgment). The treatment was repeated every 21 days. Up to 6 cycles of therapy were planned. After the first cycle, dose-limiting toxicity (DLT) was assessed to determine the MTD of PLM60 in the GVM±R regimen. Results: As of July 15, 2023, the study had enrolled 12 eligible patients (DL1: n=6, DL2: n=6), with different aNHL subtypes, including 6 with diffuse large B-cell lymphoma, not otherwise specified (DLBCL, NOS), 3 with angioimmunoblastic T-cell lymphoma (AITL), 2 with PTCL, NOS, and 1 with sezary syndrome (SS). The median age of the patients was 49 years (range, 23 to 69), with 41.7% being male. All patients had advanced-stage disease, with 33.3% in stage III and 66.7% in stage IV. They had received a median of 2.5 lines of therapy (range, 2 to 7), and 91.7% (11/12) of patients had received anthracycline-containing chemotherapy in their prior treatment. All patients with DLBCL, NOS had received rituximab during their prior therapy. 66.7% (8/12) of the patients were refractory to their last line therapy, and 2 out of the 6 patients with DLBCL, NOS experienced relapse after anti-CD19 chimeric antigen receptor T-cell (CAR-T) therapy. During the study, two patients experienced DLTs of grade 4 neutropenia lasting for more than 7 days, with one occurring in the DL1 group and the other in the DL2 group. In response to these observations, an additional three patients were enrolled in each of the groups. The most common grade 3/4 TRAEs with an incidence ≥10% were leucopenia (91.7%), neutropenia (83.3%), thrombocytopenia (66.7%), anemia (41.7%), febrile neutropenia (25.0%), pneumonia (25.0%), and hypokalemia (25.0%). With a median follow-up of 2.5 months, 11 patients were evaluated for efficacy, showing an ORR of 72.7% (95% CI 39.0% to 94.0%) and a CRR of 45.5% (95% CI 16.8% to 76.6%). In the DL1 group (16 mg/m 2), the CRR was 50.0% (3/6), and the ORR was 66.7% (4/6), while the DL2 group (18 mg/m 2) had a CRR of 40.0% (2/5) and an ORR of 80.0% (4/5) (Table 1). Among the DLBCL patients, the CRR was 60.0% (3/5), and among AITL patients, the CRR was 66.7% (2/3). Patients with PTCL NOS and SS achieved partial responses (PR). Two DLBCL patients who had previously received multiple lines of therapy, including anti-CD19 CAR T-cell therapy, achieved CR after GVM±R treatment. Conclusions: The GVM±R regimen exhibited manageable safety and encouraging efficacy in patients with r/r aNHL, despite the fact that the majority of these patients had received anthracycline-containing chemotherapy in their previous treatment. The trial is still ongoing to determine the recommended phase 2 dose for the subsequent phase 2 clinical study.

TBI/Ratg-Based Conditioning for Haploidentical Allogeneic Hematopoietic Stem Cell Transplantation in 11 Cases of Chemotherapy-Resistant Advanced-Stage Peripheral T-Cell Lymphoma

Objectives: To evaluate the clinical outcomes and safety of haploidentical allogeneic hematopoietic stem cell transplantation(haplo-HSCT)with total body irradiation (TBI)/rabbit Anti-thymocyte globulin (rATG) based conditioning regimen in chemotherapy-resistant advanced-stage peripheral T-cell lymphoma (PTCL). Methods: From September 2019 to December 2022, eleven chemotherapy-resistant advanced-stage PTCL patients who underwent haplo-HSCT were enrolled in our study. All of them received TBI/rATG-based conditioning regimen in our centers. Results: ①Among 11 patients, there were 6 males and 5 females with a median age of 40(range：22~58) years old. Six cases of them are peripheral T-cell lymphoma not otherwise specified (PTCL NOS), 3 cases are angioimmunoblastic T-cell lymphoma (AITL), 1 case is large-cell transformation of mycosis fungoides (MF-LCT), and 1 case is T-cell large granular lymphocytic leukemia(T-LGLL). The Lugano stage was III or IV in all cases, and 8 patients had B symptoms. The median number of previous chemotherapy exposure before transplantation was 4 (range: 2~10) lines and the disease status before transplantation was progressive diseases (PD) in all cases. The median time from diagnosis to transplantation was 17(range：6~36) months.②The conditioning regimen consisted of TBI 2Gy d-8, 4Gy from day-7 to -6, rATG 2.5 mg/kg/d day-5 to -2, etoposide 15mg/kg/d day-5 to -4, cyclophosphamide (CTX) 50mg/kg/d, day-3 to -2. The patients with central nervous system involvement received a regimen of thiotepa 5 mg/kg/d， from day -5 to -4 instead of CTX and etoposide, and add 2.0 g/m2 of cytarabine twice a day, from day -3 to day -2 into the conditioning.③All patients were successfully engrafted. Only one patient developed Grade III-IV acute graft-vs-host disease (aGvHD). Among the 8 survivors, 4 cases developed chronic graft-vs-host disease (cGvHD).④After transplantation, CR was obtained in 9 patients. ⑤Regimen related toxicities: all were non-fatal. Hematopoietic suppression occurred in all patients after conditioning. Three patients had diarrhea and four had mucositis and three had elevated transaminase/bilirubin levels. Seven patients had infections.⑥The 1-year cumulative non-relapse mortality (NRM) and 1-year cumulative incidence of relapse (CIR) was 22.5±14.0% and 20.2±12.7%, respectively. The 1-year overall survival (OS) and 1-year disease-free survival (DFS) was 72.7±13.4% and 63.6±14.5%, respectively Conclusions: TBIand rATG based conditioning regimen is effective and safe for haplo-HSCT in chemotherapy-resistant advanced-stage PTCL.

Impact of Front-Line Treatment Interim PET/CT in Peripheral T-Cell Lymphoma Patients' Survival: Experience of a Single Center

Introduction: The introduction of PET/CT in the staging and response assessment to therapy has changed the clinical evaluation of most lymphomas, especially Hodgkin lymphoma and aggressive B-cell lymphomas. The use of PET/CT in the staging of peripheral T-cell lymphomas (PTCL) is already a standard of care in many centers, although its decisional role in course of chemotherapy or at the end of treatment remains unclear. Objective: The aim of this study is to evaluate the predictive role of interim PET/CT in newly diagnosed PTCL patients. Methods: We retrospectively analyzed the clinical data of adult patients diagnosed with PTCL and actively treated between 2014 and 2023 at our center. All patients were evaluated with PET/CT at different timepoints (baseline, interim and end of treatment). Results: We evaluated 49 patients, with a median age at diagnosis of 59 years (range: 18-83), and a slight predominance of females (54%) (table 1). Almost half of the patients were diagnosed of angioimmunoblastic/T-follicular helper lymphoma (AITL/TFHL) 23(47%), followed by anaplastic large cell lymphoma (ALCL) in 17 cases [9 ALK+ (18%) and 8 ALK- (17%))] and peripheral T-cell lymphoma NOS (PTCL-NOS) in 9 (18%). Seven (14%) patients had ECOG ≥ 2, 47 (90%) had stage III-IV disease, among them, 42 (84%) with extranodal involvement. Bone marrow was involved in 14 out of 36 (39%) evaluated patients. Twenty-seven (54%) patients had IPI score 3-5. Front-line treatment consisted in CHOP in 32 (65%) patients and brentuximab vedotin+CHP in 17 (35%). Interim evaluation was performed after 3 cycles in 32 (65%) and after 4 cycles in 16 (33%) patients. Only one patient was evaluated after 2 cycles due to suspected disease progression. At this time point, 31 (63%) patients were considered in complete metabolic response (CMR) with a Deauville Score (DS) 1-3, 12 (25%) in partial metabolic response (PMR) with a DS 4 and 6 (12%) patients with progressive disease (PD) with DS5. Among the latter's, 4 patients were treated with 2 nd line treatment, while 2 completed the planed 6 cycles due to significant tumor burden . Among 48 patients evaluated after 3 and 4 cycles of therapy, CMR was achieved in 18 (56%) and 13 (81%), respectively (p=0,088). Eleven (34%) and one (6%) pts were in PMR at iPET after 3 and 4 cycles, respectively. Forty-five (92%) patients completed front-line therapy and were evaluated with EOT PET/. CMR (DS1-3) was reported in 32 (71%) patients, PMR in 8 (18%) and PD in 5 (%). Among patients with CMR at iPET, 25 (81%) maintained CMR, 5 (16%) converted to PMR and only 1 (3%) progressed. Among patients with PMR at iPET, 5 (42%) converted to CMR, 4 (33%) maintained PMR and 3 (25%) progressed. Eighteen (37%) patients were consolidated with autologous stem cell transplantation, all in CMR at EOT, except for 1 patient with PMR DS4. With a median follow-up of 28 months (range: 2-107 months), 25 (51%) patients relapsed or progressed. Median progression-free survival (PFS) of the entire population was 24 months. According to interim response, median PFS of DS1-3, DS4 and DS5 were 28, 10 and 2 months, respectively (Figure 1). In univariate analysis, along traditional prognostic factors as advance stage (p=0.0324), increased LDH (0.0211), IPI ≥ 3 (0.0198) and bone marrow infiltration (0.0475), interim PET/CT (iPET) impacted on PFS (DS1-3 vs DS4 vs DS5, p=0.004; DS1-3 vs DS4-5, p=0.0233). When considering the exact timing, iPET after 4 cycles seemed to relate better with PFS (DS1-3 vs DS4 vs DS5, p=0.0009) than after 3 cycles (DS1-3 vs DS4 vs DS5, p=0.32). In the multivariate analysis, iPET/CT response maintained its prognostic significance (for DS1-3 vs DS4 vs DS5: HR 2.37, 95% CI 1,44-3,89, p=0,). Median OS was not reached. The estimated 2-year OS for the entire population was 75% (95% CI, 58-86). According to iPET, the estimated 2-year OS for DS1-3, DS4 and DS5 were 85% (60-95), 64% (30-85) and 63% (14-90), respectively. No impact of iPET was documented on . Conclusion: Our study highlights the potential role of interim PET/CT in the management of PTCL. Reaching an early metabolic complete remission seems to be associated with longer PFS. Patients with a DS4 at interim evaluation remain challenging for clinicians, since also in our study half of them converted to CMR at the end of . Further radiomics analysis may help to better identify patients at higher risk of progression and offer a more tailored treatment.

Outcome of combined modality treatment in first-line for stage I(E) peripheral T-cell lymphoma; a nationwide population-based cohort study from the Netherlands.

Peripheral T-cell lymphomas (PTCL) comprise a heterogeneous group of mature T-cell neoplasms with an unfavorable prognosis; presentation with stage I(E) disease is uncommon. In clinical practice, an abbreviated chemotherapy treatment regimen combined with radiotherapy (combined modality treatment [CMT]) is commonly used, although evidence from clinical trials is lacking. The aim of this nationwide population-based cohort study is to describe first-line treatment and outcome of patients with stage I(E) PTCL. All newly diagnosed patients ≥18 years with stage I(E) anaplastic large cell lymphoma (ALCL), angioimmunoblastic T-cell lymphoma (AITL) and peripheral T-cell lymphoma NOS (PTCL not otherise specified [NOS]) in 1989-2020 were identified in the Netherlands Cancer Registry. Patients were categorized according to treatment regimen, i.e., chemotherapy (CT), radiotherapy (RT), CMT, other therapy and no treatment. The primary endpoint was overall survival (OS). Patients with stage I(E) ALCL, AITL and PTCL NOS (n=576) were most commonly treated with CMT (28%) or CT (29%), 2% underwent SCT. RT only was given in 18%, and 8% received other therapy and 16% no treatment. Overall, the 5-year OS was 59%. According to subtype, 5-year OS was superior for ALCL as compared to PTCL NOS and AITL (68% vs. 55% and 52%, respectively; P=0.03). For patients treated with CMT, 5-year OS was significantly higher (72%) as compared to patients treated with either CT or RT alone (55% and 55%, respectively; P<0.01). In multivariable analysis, age per year increment (hazard ratio [HR] =1.06, 95% confidence interval [CI]: 1.05-1.07), male sex (HR=1.53, 95% CI: 1.23-1.90), and CT, or no treatment (HR=1.64, 95% CI: 1.21-2.21, and HR=1.55, 95% CI: 1.10-2.17, respectively) were associated with a higher risk of mortality. For stage I(E) ALCL, AITL and PTCL NOS, 5-year OS is 59%, comparing favorably to historical outcome in advanced-stage disease. Superior outcome estimates were observed in patients treated with CMT.

Endoscopic features of colorectal lymphoma according to histological type.

Background and AimThis study aimed to investigate the relationship between the histological type of colorectal lymphoma and its endoscopic features.MethodsWe retrospectively analyzed patients with primary colorectal lymphoma who were diagnosed using colonoscopy and biopsy specimens at the National Cancer Center Hospital, Tokyo, Japan. The lesions were macroscopically classified into the following types via colonoscopy: polypoid, ulcerative, multiple lymphomatous polyposis, diffuse, and mixed.ResultsA total of 117 lesions were identified in 90 patients enrolled in this study. Of these, 59 (50%) were located in the ileocecal region, 23 (20%) in the rectum, 9 (8%) in the transverse colon, 8 (7%) in the sigmoid colon, 7 (6%) in the descending colon, and 4 (3%) in the ascending colon. Moreover, the most common histological subtypes were diffuse large B‐cell lymphoma (DLBCL) in 39 patients (43%) and mantle cell lymphoma (MCL) in 23 patients (26%), followed by follicular lymphoma (FL; 17%), mucosa‐associated lymphoid tissue (MALT) lymphoma (9%), peripheral T‐cell lymphoma‐NOS (2%), monomorphic epitheliotropic intestinal T‐cell lymphoma (MEITL; 2%), and Burkitt lymphoma (1%). More than half of the DLBCL (52%), MCL (52%), and MALT (56%) lymphomas were macroscopically classified as polypoid types. In contrast, FL lesions showed various macroscopic types. The majority of DLBCL (62%) and FL (78%) lesions were distributed in the ileocecal region. MCL lesions tended to be widely spread in various sites of the large intestine.ConclusionsColorectal lymphomas showed macroscopically distinctive features depending on the histological type. Understanding the macroscopic classification of the lesions by colonoscopy and its distribution may be helpful in diagnosing the type of lymphoma and determining the malignant grade based on the histological types.

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

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. DisclosuresVan 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.

Successful Treatment of Mature T-Cell Lymphoma with Allogeneic Stem Cell Transplantation: The Largest Multicenter Retrospective Analysis

Successful Treatment of Mature T-Cell Lymphoma with Allogeneic Stem Cell Transplantation: The Largest Multicenter Retrospective Analysis

Distribution of Lymphomas in Mexico: A Descriptive Study

IntroductionLymphomas are a heterogeneous group of hematological malignancies of which incidence, prevalence, and epidemiological factors are still not well described in the Mexican population. Most of the recent descriptive studies do not specify details of their analysis and were not based on the WHO classification of tumours. In our study we analyzed 5772 lymphomas diagnosed over a period of 10 years between 2005 and 2014, and classified them according to the 2008 WHO Classification of Tumours of Lymphoid Tissues. The aim of our study is to determine frequencies and subtypes of the main non-Hodgkin's and Hodgkin's lymphomas in a heterogeneous sample of biopsies in the Mexican population.MethodsFiles for tissue samples for lymphomas stored in 5 different hospitals in Mexico City were retrieved for re-analysis. All cases where tissue samples were available were stained with hematoxylin and eosin as well as immunostained. Analysis was performed to differentiate the main mature B-cell, T-cell, Hodgkin's, and precursor lymphoid neoplasms according to the 2008 WHO classification of tumours. Age and sex were obtained and registered from the original submitted request for pathology assessment. All stains were performed in the same laboratory and interpreted by 3 pathologists who provided a diagnosis.Results5772 neoplasms were included in this study. Of these, 4213 were mature B-cell neoplasms (73%; 95%CI 71.83 - 74.12), 888 Hodgkin's lymphomas (HL) (15%; 95%CI 14.48 - 16.34), 496 mature T-cell / NK neoplasms (9%; 95%CI 7.89 - 9.34), and 175 precursor lymphoid neoplasms (3%; 95%CI 2.62 - 3.5). Neoplasms had an even distribution between sexes, with 51% of the cases being male patients.All 4 different categories of neoplasms were further analysed and classified. Six main mature B-cell lymphomas accounted for almost 95% of our cohort. These included diffuse large B-cell lymphoma (DLBCL) (56%; 95%CI 54.39 - 57.39), follicular lymphoma (FL) (20%; 95%CI 18.92 - 21.34), mantle cell lymphoma (6.7%; 95%CI 6.02 - 7.53), marginal zone/MALT lymphoma (5.2%; 95%CI 4.59 - 5.93), chronic lymphocytic leukemia/small lymphocytic lymphoma (4.6%; 95%CI 4.01 - 5.28), and Burkitt's lymphoma (2.5%; 95%CI 2.04 - 2.98). Hodgkin's lymphomas were also classified in 6 main subtypes, with nodular sclerosis (47%; 95%CI 44.14 - 50.7) and mixed cellularity (38%; 95%CI 34.49 - 40.85) being the most common. Several mature T-cell / NK neoplasms were identified, with the majority of cases being peripheral T-cell lymphoma NOS / anaplastic large cell lymphoma ALK negative (44%; 95%CI 39.85 - 48.84) and extranodal NK/T-cell lymphoma, nasal type (30%; 95%CI 25.5 - 33.76). Please refer to Table 1, 2, and 3 for further information.Analysis of cases by group age was also performed for mature B-cell neoplasms and HL. As expected, the majority of cases of DLBCL were seen in the age groups of 41-60 as well as 61-80. The same applied to FL. In the case of HL, the majority of nodular sclerosis subtypes were seen in the group age of 21-40 and mixed cellularity subtype showed a more even distribution in the age groups between 21-80.ConclusionTo our knowledge, this is the first descriptive study with a large sample of confirmed lymphoid neoplasms, using a standardized method of staining, classified according to the 2008 WHO Classification of Tumors representative of the Mexican population. It is a complement to the current epidemiologic registry of neoplasms in Mexico, adding classification details according to global standards set by the WHO. The results obtained are in keeping with the numbers described in other population studies worldwide. [Display omitted] DisclosuresLazo-Langner:Bayer: Honoraria; Pfizer: Honoraria; Daiichi Sankyo: Research Funding; Alexion: Research Funding.

Impact of Comorbidities on Outcomes of Peripheral T Cell Lymphoma in Elderly Patients: An International Retrospective Study

Background: Peripheral T cell lymphoma (PTCL) is a heterogeneous group of aggressive lymphoid neoplasms with poor outcomes. Many patients are elderly with increased comorbidities. Single-center retrospective studies describe outcomes in elderly PTCL patients and suggest comorbidity adversely affects outcomes. Little is known about the treatment, outcomes and impact of comorbidity in a large cohort of elderly PTCL patients. This study aims to describe outcomes of elderly PTCL patients in a large unselected international patient cohort. Methods: Patients with PTCL age ≥ 70 diagnosed from January 1, 2010 - December 31, 2015 in the Swedish Lymphoma Registry (SLR) and California Cancer Registry (CCR) were identified. The SLR covers ~ 95% of adult lymphoma patients in Sweden and the CCR includes information on all cancers diagnosed in California. Patients with precursor T-cell malignancies, primary cutaneous lymphomas, and leukemic subtypes were excluded. Data on comorbidity at diagnosis were retrospectively collected according to the Charlson Comorbidity Index (CCI) and clinical outcomes of the cohort were extracted. Statistical analysis: Patient characteristics, clinical variables and outcomes were summarized using descriptive statistics and compared by Chi-square or Fisher's exact test. Outcomes of interest included overall survival (OS) and cause of death. Kaplan-Meier estimates of OS stratified by groups were calculated and presented in figures. Median OS was reported with 95% confidence interval (CI). Comparisons between groups for OS were done by log-rank test. Univariate and multiple Cox proportional hazards models provided hazards ratio estimates and 95% CI for risk factors. Tests for significance were two-tailed and a p-value less than the 0.05 significance level was considered statistically significant. Analyses were performed using software SAS version 9.4 (2013). Results: A total of 839 patients were included (SLR, n = 176, CCR, n = 663). Median age was 78 (SLR) and 79 (CCR) years, respectively. Included subtypes were AITL, n = 226; ALCL, n = 122; EATL, n = 31; Hepatosplenic TCL, n = 7; NK/T-cell lymphoma, n = 10; and PTCL NOS, n = 443. ECOG performance status was not available. CCI data was available in 731 patients (87 %), and CCI scores were divided into groups = 0-1 (61 %) and CCI &amp;gt; 1 (39 %). Male patients more often had a CCI score &amp;gt; 1 (p = 0.024). No other significant baseline differences were seen between the 2 groups (Table 1). Patients in the SLR more often received multiagent treatment compared to the CCR (63 % vs 44 %, p &amp;lt; 0.001). Age &amp;gt; 80 years, CCI &amp;gt; 1 and advanced Ann Arbor stage (III-IV) were significant prognostic factors for worse outcome. No difference in survival was seen between men and women nor the SLR and CCR (Table 2). Patients with a CCI &amp;gt;1 had a statistically significant worse survival compared to patients with a CCI =0-1 (0.36 years v 0.91 years, p=0.0001). Of the PTCL subtypes, AITL patients had a significantly better outcome (median OS = 1.26 years) compared to ALCL (OS = 0.57 years) and PTCL NOS (OS = 0.66 years). Patients receiving multiagent therapy had improved survival compared to patients not receiving multiagent therapy. When comparing OS in patients diagnosed in 2010-2012 with 2013-2015, no improvement was seen for the later period (Figures 1-4). Lymphoma was the most common cause of death with &amp;gt; 70 % of deaths related to lymphoma irrespective of CCI score (Table 3). Discussion: At the time of submission, this study presents the largest international cohort of elderly patients with PTCL. Prognosis is poor and comorbidity seems to further worsen . In contrast to younger patient series, patients with AITL had a better survival than patients with PTCL NOS and ALCL, and were more common in the CCR than in the SLR. Multiagent treatment was associated with improved outcome. A possible confounder could be that fit patients are also the ones receiving treatment, and it is a setback that adjustment for ECOG was not possible, making treatment data somewhat difficult to interpret. As expected, advanced stage (Ann Arbor III-IV) was associated with worse survival. Conclusion: We believe this is one of the largest cohorts presented in elderly patients with PTCL. Comorbidity is an important adverse factor in this group, whereas treatment seems to improve outcome. The majority of these patients die of lymphoma within a year from diagnosis, and development of new treatments represents an unmet clinical need. Disclosures Jerkeman: Abbvie: Research Funding; Gilead: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Roche: Research Funding.

Nivolumab in Combination with Gemcitabine and Oxaliplatin (GemOx) in Relapse/Refractory T-Cell Lymphoma: Preliminary Results of the Experimental Arm of the Niveau Trial

Nivolumab in Combination with Gemcitabine and Oxaliplatin (GemOx) in Relapse/Refractory T-Cell Lymphoma: Preliminary Results of the Experimental Arm of the Niveau Trial

Trial-in-Progress: Frontline Brentuximab Vedotin and CHP (A+CHP) in Patients with Peripheral T-Cell Lymphoma with Less Than 10% CD30 Expression

Background In the ECHELON-2 phase 3 clinical trial, brentuximab vedotin, cyclophosphamide, doxorubicin, and prednisone (A+CHP) showed clinically meaningful and statistically significant efficacy in patients with peripheral T-cell lymphoma (PTCL) across a range of CD30 expression levels, including the lowest eligible level of 10% by IHC. In addition to the ECHELON-2 study, response data are available from an additional 344 subjects with CD30-expressing PTCL and other large-cell lymphomas (including angioimmunoblastic T-cell lymphoma and peripheral T-cell lymphoma-NOS) who had been treated in studies with brentuximab vedotin as a single agent or in combination with chemotherapy, in both frontline and relapsed/refractory settings. Among these 344 subjects, 184 had tumors with CD30 expression &amp;lt;10% by local assessment, including 83/184 with undetectable CD30 by immunohistochemistry (CD30=0). Responses to brentuximab vedotin have been observed at all levels of CD30 expression, including in tumors with undetectable CD30 levels (Advani 2019; Horwitz 2019). It is hypothesized that A+CHP will demonstrate efficacy in subjects with PTCL and CD30 expression &amp;lt;10% because: i) brentuximab vedotin has shown activity in lymphomas with low CD30 expression; and ii) the activity of CHP chemotherapy in PTCL is unrelated to CD30 expression. This study will include subjects with PTCL subtypes other than systemic anaplastic large cell lymphoma (sALCL). Study Design and Methods This is a dual-cohort, open-label, multicenter, phase 2 clinical trial designed to evaluate the efficacy and safety of A+CHP in subjects with non-sALCL PTCL and CD30 expression &amp;lt;10% on tumor cells. Enrollment will be based on CD30 expression per local lab assessment. Subjects will be assigned to 1 of 2 cohorts based on CD30 expression; up to approximately 40 subjects will be enrolled in the CD30 negative (expression &amp;lt;1%) cohort and approximately 40 subjects will be enrolled in the CD30 positive (expression ≥1% to &amp;lt;10%) cohort. An archived tumor biopsy specimen will be submitted to a central pathology lab for confirmation of CD30 expression. Only subjects with CD30 expression &amp;lt;10% per central confirmation will be analyzed for the primary and secondary endpoints. Subjects will receive 21-day cycles of A+CHP for a target of 6-8 cycles. The primary endpoint of this trial is objective response rate (ORR) per blinded independent central review (BICR). Key secondary endpoints include CR and PFS per BICR and overall survival. Key inclusion criteria include the following: subjects aged 18 years and older with newly diagnosed PTCL, excluding sALCL, per the WHO 2016 classification; CD30 expression &amp;lt;10% by local assessment; and fluorodeoxyglucose-avid disease by PET and measurable disease of at least 1.5 cm by CT, as assessed by the site radiologist. Lymphoma response and progression will be assessed by BICR using Revised Response Criteria for Malignant Lymphoma and modified Lugano criteria. A CT scan will be performed at the time of suspected clinical progression. Subsequent restage assessments (CT scans only) will be performed according to the calendar, relative to the first dose of study treatment, to ensure that tumor progression is uniformly assessed between the treatment arms. Efficacy and safety endpoints will be summarized with descriptive statistics by cohort, with the CD30 negative cohort and the CD30 positive cohort. The summary of overall (CD30 negative and positive cohort combined) may be presented as appropriate. Descriptive statistics (mean, median, standard deviation, minimum, and maximum) will be used to describe continuous variables. Time-to-event endpoints, such as PFS, will be estimated using Kaplan-Meier methodology and Kaplan-Meier plots will be presented. Medians for time-to-event analyses (eg, median PFS), will be presented and two-sided 95% confidence intervals will be calculated using the log-log transformation method. The trial will have sites open in the US and multiple countries in Europe, with enrollment planning to begin in September 2020. Disclosures Jagadeesh: Verastem: Membership on an entity's Board of Directors or advisory committees; Seattle Genetics: Membership on an entity's Board of Directors or advisory committees, Research Funding; MEI Pharma: Research Funding; Debiopharm Group: Research Funding; Regeneron: Research Funding. Sims:Seattle Genetics, Inc.: Current Employment, Current equity holder in publicly-traded company, Other: Travel expenses. Horwitz:ASTEX: Consultancy; Millenium/Takeda: Consultancy, Research Funding; Corvus: Consultancy; Innate Pharma: Consultancy; Mundipharma: Consultancy; Seattle Genetics: Consultancy, Research Funding; Trillium: Consultancy, Research Funding; Forty Seven: Consultancy, Research Funding; Infinity/Verastem: Research Funding; Celgene: Consultancy, Research Funding; GlaxoSmithKline: Consultancy; Aileron: Consultancy, Research Funding; ADCT Therapeutics: Consultancy, Research Funding; Janssen: Consultancy; Myeloid Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Vividion Therapeutics: Consultancy; Affirmed: Consultancy; Kura Oncology: Consultancy; Miragen: Consultancy; Kyowa Hakka Kirin: Consultancy, Research Funding; Beigene: Consultancy; C4 Therapeutics: Consultancy; Daiichi Sankyo: Research Funding; Portola: Consultancy, Research Funding.

TCL-362: Clinicopathological Profile of Peripheral T-Cell Lymphoma-NOS and Angioimmunoblastic T-cell Lymphomas

Context: Peripheral T-cell lymphomas derived from the mature T-cells are a heterogeneous group with varying biological and clinical behaviour. Objective: We analysed the epidemiological, clinical, histomorphological, immunophenotypic, and mutational characteristics of PTCLs in our centre. Design: This was a retrospective study including all cases of PTCL from 2015 to 2019 retrieved from the archive of Department of Pathology, AIIMS, New Delhi. The cases were reclassified according the WHO 2016 classification. Additional immunohistochemistry (PD1, ICOS, Bcl6 and CD10), EBERish, and mutational studies for IDHR172 and RHOA G17V) were done in cases diagnosed as PTCL-NOS and AITL. The clinical profile was correlated with the above factors and the prognostication index. Results: Of the total 441 lymphoma cases diagnosed of T-cell lineage, 35.37% were of the precursor type, and the rest were mature T-cell lymphomas. A male predominance was noted. PTCL-NOS was the most common subtype among the mature type (n=76; 17.23%) followed by ALCL, ALK+ (n=70; 15.87%), extranodal NK-/T-cell lymphomas (n=58, 13.15%), and AITL (n=16; 3.63%). They were dominant in the adult age (19–65 years, n=207), followed by pediatric and adolescents (n=43) and elderly (n=35) populations. The primary site of involvement was a mixture of nodal (n=138) and extranodal (n=147). The patients presented in advanced stages with a mean IPI score of 3/5. High LDH levels with direct Coombs test positivity was noted among AITL patients. With the help of immunohistochemistry, a few of the diagnosed PTCL-NOS were reclassified as AITL, and one of the diagnosed AITL was reclassified as PTCL with TFH phenotype. A few of the diagnosed AITL cases immunonegative for EBV-LMP1 proved their causal relationship with EBERish positivity. An overall mean survival of 20 months was noted among 30 cases with a maximal follow up of 3 years. Conclusions: A higher prevalence of immature cell neoplasm and ALCL was noted among the Indian population. Though morphologically there may be an overlap in the diagnosis among the various PTCL subtypes, immunohistochemistry and molecular studies can help in reaching the definite diagnosis. Funding: Thanks to the Science Engineering Research Board (EEQ/2016/402, ECR /2015/452) and All India Institute of Medical Science Research Section (A-653).

Clinical Remission in a 72-Year-Old Patient with a Massive Primary Cutaneous Peripheral T-Cell Lymphoma-NOS of the Eyelid, Following Combination Chemotherapy with Etoposide Plus COP

Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) is the rarest subtype of primary cutaneous lymphoma, accounting for approximately 2% of cutaneous lymphomas. The rarity of primary cutaneous PTCL-NOS means that there is a paucity of data regarding clinical and histopathological features and its clinical course. This malignancy is an aggressive and life-threatening hematological malignancy that often presents mimicking other less severe plaque-like skin conditions. Due to the nonspecific nature of these lesions, CD4-positive cutaneous T-cell lymphoma (CTCL) is often misdiagnosed as either mycosis fungoides or Sezary syndrome. We describe a patient who presented with a large tumoral mass in the right frontal area, with involvement of the right upper eyelid and the ocular globe, causing loss of vision greatly impacting the quality of life. Biopsy revealed primary cutaneous PTCL-NOS, treated successfully with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus etoposide combination chemotherapy. As elderly patients are indicated to receive attenuated doses of chemotherapy, CHOP-based regimens represent viable options.

Prevalence and spectrum of T-cell lymphoproliferative disorders in patients with Hypereosinophilia: A reference laboratory experience

Hypereosinophilia (HE) is defined as persistently elevated absolute eosinophil count (AEC) ≥ 1.5 × 109/L, which can be due to a variety of underlying causes. In this study, we investigated the prevalence and spectrum of T-cell lymphoproliferative disorders in 124 consecutive patients with HE by flow cytometric immunophenotyping. Available medical records, pathology reports and T-cell receptor (TCR) gene rearrangement were reviewed. Fifteen patients (12%) with HE had abnormal T-cell populations that were initially detected by flow cytometry. The presence of immunophenotypically abnormal T cells was not associated with higher AEC or higher absolute lymphocyte count levels, in comparison to those without abnormal T cells. Molecular studies concordantly identified a clonal TCR gene rearrangement in 8 of 10 cases tested. Based on the combination of clinical presentation, morphologic findings and laboratory studies, seven patients were diagnosed with the lymphocytic variant of hypereosinophilic syndrome and five with overt T-cell lymphoma (4 peripheral T-cell lymphoma NOS, 1 primary cutaneous T-cell lymphoma). The remaining three had an unknown diagnosis due to lack of information and additional workup would be warranted. These findings underscore the importance of flow cytometry as a screening tool to identify T-cell lymphoproliferative disorders in patients with HE.

PS1096 INTERIM UPDATE FROM A MULTI‐CENTER STUDY OF PRALATREXATE IN ASIAN PATIENTS WITH RELAPSED OR REFRACTORY(R/R) PERIPHERAL T‐CELL LYMPHOMA (PTCL)

Background:Peripheral T‐cell lymphomas (PTCL) are a group of rare, aggressive and diverse lymphoproliferative disorder. When patients are in the relapsed/refractory setting, the survival is mostly less than 6 months. Pralatrexate, a folate analogue metabolic inhibitor, was the first monotherapy approved to treat R/R PTCL patients. As the subtypes difference between western and eastern countries, we would like to investigate the efficacy/safety of pralatrexate in Taiwanese patients.Aims:This single‐arm, multi‐center study aims to demonstrate the efficacy/ safety of pralatrexate in R/R PTCL patients. The patients who undergo Hematopoietic Stem Cell Transplantation (HSCT) or not after pralatrexate will be also investigated individually.Methods:Eligibility criteria included age ≧ 20 with PTCL according to the NCCN diagnosis criteria, the Revised European American Lymphoma (REAL), and WHO disease classification with the following subtypes: Peripheral T‐cell lymphoma, NOS (PTCL‐NOS), Angioimmunoblastic T‐cell lymphoma (AITL), Extranodal NK/T‐cell lymphoma, nasal type (ENKL), Enteropathy‐type T‐cell lymphoma (EATL), Hepatosplenic T‐cell lymphoma (HSTCL), Subcutaneous panniculitis‐like T‐cell lymphoma (SPTCL) and Adult T‐cell lymphoma/leukemia (human T‐cell leukemia virus [HTLV] 1+) (ATLL). Patients were documented disease progression after prior treatment. Intravenous pralatrexate was administrated weekly for 6 weeks in 7‐week cycles up to 5 cycles with concurrent vitamin B12 and folic acid. Patients who complete at least 1 cycle of pralatrexate and have at least 1 post‐treatment tumor assessment are defined as evaluable patients. The primary end point is Objective Response Rate (ORR, CR + PR). Secondary end points include Progression‐Free Survival (PFS), Duration of response (DoR) and Overall Survival (OS).Results:Twenty‐two patients were evaluable for efficacy per protocol definition. The subtype distribution included PTCL‐NOS (n = 9, 40.9%), AITL (n = 5, 22.7%), ENKL (n = 5, 22.7%), EATL (n = 1, 4.5%), SPTCL (n = 1, 4.5%) and ATLL (n = 1, 4.5%). The ORR was 54.5% with CR 18.2% (n = 4) and PR 36.3% (n = 8). When divided into 2 groups based on if patients received HSCT after pralatrexate, the ORR in HSCT group (n = 5) was 60% with CR 20% (n = 1) and PR 40% (n = 2), while ORR in non‐HSCT group (n = 17) was 53% with CR 18% (n = 3) and PR 35% (n = 6). At the time of data cut‐off, median PFS was 5 months (95% C.I. 5.51, 12.93), median DOR was 5.4 months (95% C.I. 2.64, 13.10) and OS not reached yet. It's notably that, among 5 patients that received HSCT successfully after pralatrexate, 4 patients are ENKL and the other is PTCL‐NOS. Except one who experienced disease progression after HSCT, the others still remain in response. It indicated that pralatrexate may play a beneficial role in bridging to transplantation in PTCL patients, especially in ENKL. Safety population analysis (n = 27) showed the most common TEAEs (grades 3–4) were: anemia (33%), stomatitis (26%), peripheral edema (22%), thrombocytopenia (15%) and leukopenia (11%).Summary/Conclusion:This interim update of this multi‐center study demonstrated the efficacy of pralatrexate monotherapy in R/R PTCL is 54.5%. Interestingly, most ENKL patients received HSCT after obtaining good disease control with pralatrexate. In addition, it showed tolerable safety profile. This is the first data demonstrated benefits of pralatrexate in R/R PTCL patients with intention or no intention to receive transplantation.image

S869 TIPIFARNIB IN RELAPSED OR REFRACTORY ANGIOIMMUNOBLASTIC T‐CELL LYMPHOMA (AITL) AND CXCL12+ PERIPHERAL T‐CELL LYMPHOMA (PTCL): PRELIMINARY RESULTS FROM AN OPEN‐LABEL, PHASE 2 STUDY

Background:Tipifarnib is a potent and selective inhibitor of the enzyme farnesyltransferase (FT). FT catalyzes post‐translational attachment of farnesyl groups required for localization of signaling molecules to the inner cell membrane. CXCL12 is a chemokine that is essential for T cell homing to lymphoid organs and the bone marrow, and for the maintenance of immune cell progenitors.Aims:Herein we report preliminary efficacy, safety and biomarker data from a Phase 2 study of tipifarnib in angioimmunoblastic T‐cell lymphoma (AITL) and CXCL12+ peripheral T‐cell lymphoma (PTCL) patients (pts).Methods:This Phase 2 study (NCT02464228) is a multi‐institutional, single‐arm, open‐label trial initially designed as a two‐stage (11+7 pts) design to determine the efficacy, safety and biomarkers of tipifarnib in pts with relapsed/refractory (R/R) PTCL age &gt;/ = 18 years and a performance status of 0–2. Based on initial findings, the study was amended to include a cohort of AITL (n = 12) and PTCL (n = 12) pts with the CXCL12 rs2839695 A/A genotype (CXCL12+ cohort). Pts received tipifarnib 300 mg administered orally twice daily on days 1–21 of 28‐day treatment cycles until progression of disease (PD) or unacceptable toxicity. The primary endpoint of the study is overall response rate (ORR). Ancillary studies are also ongoing to investigate the prognostic value of CXCL12 expression in pts who received tipifarnib and standard of care treatment.Results:As of 20 February 2019, 43 PTCL pts (20 AITL, 21 PTCL‐NOS, 1 ALK‐ ALCL, 1 gamma‐delta TCL) have been treated with tipifarnib, 19 pts in stages 1 and 2, and 24 pts in the ongoing AITL histology and CXCL12 cohort. Median number of prior treatment regimens was 3; 19 pts had a prior stem cell transplant. All pts had at least one treatment‐emergent adverse event (TEAE); 39 (90%) had at least 1 study drug‐related TEAE and 12 (28%) at least 1 drug related SAE. The most frequently observed drug‐related TEAEs of Grade ≥3 occurring in 10% or more of pts were blood and lymphatic system disorders, including neutropenia (44%), thrombocytopenia (37%), leukopenia (28%), anemia (21%) and febrile neutropenia (21%). There have been 14 deaths on study; none were related to study drug. Of 18 evaluable pts enrolled in Stages 1 and 2 of the trial, 3 partial responses (PR), 2 of them in pts with AITL histology, and 4 best responses of stable disease (SD) were observed. In the AITL cohort (11 evaluable pts), a 45% ORR and 73% clinical benefit rate (CBR; 3 CR, 2 PR and 3 SD) was observed. In the CXCL12+ cohort (n = 3 evaluable pts), 1 PR and 2 SD have been observed, with 4 pts pending cycle 2 response evaluation. CXCL12 expression correlated with favorable outcome to tipifarnib treatment. Pre‐treatment high CXCL12 expression had 90% sensitivity and 93% specificity to identify pts who experienced CR/PR/SD on study in a preliminary analysis of 24 pts. The prognosis of CXCL12 was also retrospectively investigated in 73 pts who received standard of care therapy (AITL N = 50, PTCL NOS = 23). A trend for poor prognosis (22 vs 40 months median OS from diagnosis, HR = 1.8, p = 0.09) was observed using the high CXCL12 subset using the cut‐off point that predicted clinical benefit under tipifarnib therapy. Fifty percent of AITL and 35% of non‐AITL samples overexpressed CXCL12.Summary/Conclusion:Preliminary activity of tipifarnib was observed in PTCL pts, particularly in those with tumors of AITL histology and high CXCL12 expression and enrollment in the CXCL12+ cohort continues.

Alemtuzumab Added to CHOP for Treatment of Peripheral T-Cell Lymphoma (PTCL) in Previously Untreated Young and Elderly Patients: Pooled Analysis of the International ACT-1/2 Phase III Trials

Background: Standard treatment in PTCL pts is unsatisfactory due to a high rate of early progression. Alemtuzumab (A), a monoclonal anti CD52 antibody, has demonstrated efficacy in relapsed PTCL pts. The results of the final analyses of the ACT-1 phase III and the ACT-2 phase III trial, comparing standard CHOP to A-CHOP showed higher response rates, but did not yield significant differences in EFS, PFS and OS in both previously untreated young and elderly patients, but the planned sample sizes could not be reached due to low recruitment. We undertook a planned pooled analysis of both ACT trials comparing CHOP with A-CHOP to increase statistical power.Patients and Methods: Between 2007 and 2013, 252 pts from Austria, Belgium, Czech Republic, Denmark, Finland, France, Germany, Norway, Poland, Portugal, Sweden and The Netherlands were randomized to receive either 6 cycles CHOP or A-CHOP at 14 day intervals. The planned pooled analysis was performed to compare patient outcome adding A to CHOP with patients treated with CHOP alone. Primary endpoint within ACT-1 and ACT-2 trial was the 3 years event free survival (EFS), secondary endpoints were progression free survival (PFS) and overall survival (OS). EFS is defined as the time from randomization to disease progression, start of salvage treatment, additional (unplanned) treatments, relapse, or death of any cause.Results: 252 pts were randomized (ACT-1: 136; ACT-2: 116). Five patients received no study treatment; therefore, 247 pts were analyzed (CHOP: 124; A-CHOP: 123). Median age was 61 years. 62% were male. Histologies were 33% AITL, 34% PTCL NOS, 33% other subtypes. In the pooled data set, the two treatment groups were comparable. Infections grade ≥3 occurred more often in patients treated with Alemtuzumab (A-CHOP: 55% [95% CI: 45% - 64%] vs. CHOP 23% [16% - 32%]; p<0.001). Complete remissions were achieved in 56% [47% - 65%] of A-CHOP and 43% [34% - 52%] of CHOP pts (p=0.036). However, EFS (A-CHOP at 3 yrs: 32% [23% - 40%] vs. CHOP 25% [17% - 33%]; p=0.159), PFS (33% [25% - 42%] vs. 27% [19% - 35%]; p=0.220) and OS (46% [37% - 55%] vs. 53% [44% - 62%]; p=0.332) showed no significant differences. Multivariate analyses, adjusted for IPI factors, bulky disease and gender, confirmed these results (hazard ratio HREFS: 0.8 ([95% CI: 0.6 - 1.1]; p=0.196), HRPFS: 0.8 ([95% CI: 0.6 - 1.1]; p=0.246), HROS: 1.2 ([95% CI: 0.8 - 1.6]; p=0.370). Male gender (HR 2.5), ECOG > 1 (HR 2.1) and bulky disease (HR 2.1) were the most prominent unfavorable risk factors for EFS. With the sample size of 247 pts the power for detecting the planned EFS difference of 15% was 74%.Conclusion: Adding Alemtuzumab to CHOP increased the rate of CR in PTCL patients, albeit at the costs of higher treatment related toxicity. Addition of Alemtuzumab did not improve EFS, PFS, or OS. Female gender is associated with a significantly better prognosis. This is the largest prospective dataset collected for PTCL.Supported by Federal Ministry of Research BMBF FKZ 01KG0705 and unrestricted research grants by Genzyme-Sanofi and AMGEN DisclosuresNo relevant conflicts of interest to declare.

Clinical Characteristics and Outcomes of an Analysis of a Single Institution Experience of the 2017 World Health Organization (WHO) Classification of Post-Transplant Lymphoproliferative Disorders (PTLD)

Background: PTLD is the most common malignancy, other than non-melanoma skin cancer, complicating solid organ transplantation (SOT) and has been one of the most commonly observed fatal consequences in SOT. The clinical presentations, management strategies, histologies, causes of death and outcomes are diverse (Dierickx D, Habermann TM. N Engl J Med 2018;378:549-62). The 2017 WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues has redefined the categories as non-destructive PTLDs (plasmacytic hyperplasia, infectious mononucleosis, and florid follicular hyperplasia), polymorphic PTLD, monomorphic PTLD: B-cell neoplasms (diffuse large B-cell lymphoma, Burkitt lymphoma, high-grade B-cell lymphoma, plasmablastic lymphoma, plasma cell myeloma, plasmacytoma, and other) and T-cell neoplasms (peripheral T-cell lymphoma NOS, hepatosplenic T-cell lymphoma, other), and classic Hodgkin lymphoma (CHL) PTLD. We report the outcomes and long-term follow-up of patients from a single institution based on these categories whose pathology was retrospectively reviewed and reclassified based on the WHO 2017 classification.Methods: Patients with SOT who were diagnosed with PTLD at Mayo Clinic (Rochester, MN) were identified through the Mayo Clinic Lymphoma Data base and the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER). The histology was re-reviewed in 80% of the cases (RLK) and classified according to the WHO Classification of Tumours of Haematopoietic an Lymphoid Tissues 2017. Cases were considered “PTLD, unclassified” if the histology could not be confidently classified based on pathology material available for review. Indolent small B-cell lymphomas were not included among the PTLDs except for EBV-positive marginal zone lymphoma. Cox proportional hazards models were used to assess the association of clinical factors in overall survival (OS).Results: 233 patients diagnosed with PTLD between 1987 and 2017 were identified. The median age at the time of diagnosis of PTLD was 54 years (range 16 to 84) with 85 patients (36%) over the age of 60. 156 (67%) were male. The transplanted organs were kidney (41%), kidney/pancreas (5%), liver (29%), heart (9%), lung (7%), and other (8%). PTLD occurred late (more than one year after transplantation) in 66%. There were 69 stage I, 19 stage II, 8 stage III, and 128 stage IV patients. 84% presented with extranodal disease. 21% had involvement of the engrafted organ. 64% of the patients developed a PTLD that was EBV positive by in situ hybridization. Initial approaches to management included reduction of immunosuppression (N=55), chemotherapy/immunochemotherapy (N=71), reduction in immunosuppression with rituximab (N=58), single agent rituximab (N=14), and radiation therapy (N=5). At a median follow-up of 87 months (range 9-289), 139 (60%) patients had died. All six CHL-PTLD patients are alive, two of whom had an event. The median overall survival (OS) was 85 months (95% CI: 39-144) in 177 monomorphic B-cell lymphoma PTLD, 95.5 months (95% CI: 40-not reached) in 24 polymorphic PTLD, and 60 months in 8 non-destructive PTLD cases. In contrast, the median overall survival was 12 months (95% CI: 4-200) in 8 monomorphic T cell and 3 months (95% CI: 1-unreached) in 9 unclassified PTLD cases.Conclusion: PTLD is a heterogeneous group of immunodeficiency-associated lymphoproliferative disorders. The overall survival in non-destructive, polymorphic, and monomorphic PTLD were similar. Monomorphic T/NK cell types had inferior outcomes. [Display omitted] DisclosuresMaurer:Morphosys: Research Funding; Nanostring: Research Funding; Celgene: Research Funding. Ansell:Celldex: Research Funding; Merck & Co: Research Funding; Takeda: Research Funding; LAM Therapeutics: Research Funding; Seattle Genetics: Research Funding; Trillium: Research Funding; Bristol-Myers Squibb: Research Funding; Affimed: Research Funding; Regeneron: Research Funding; Pfizer: Research Funding. Cerhan:Celgene: Research Funding; Nanostring: Research Funding; Jannsen: Other: Scientific Advisory Board.

Hematopoietic Stem Cell Transplant in Novel Agent Era Is Associated with Improved Survival in Relapsed and Refractory Peripheral T-Cell Lymphoma

BackgroundConventional salvage chemotherapy has limited efficacy in relapsed or refractory (R/R) peripheral T-cell lymphoma (PTCL). In the last decade, several novel agents, including pralatrexate, an antifolate, brentuximab vedotin (BV), a CD30-directed antibody-drug conjugate, and romidepsin, a histone deacetylase inhibitor, have been introduced into clinical practice based on phase 2 data demonstrating efficacy in relapsed/refractory (R/R) diseases. Their impact on real world survival remains to be defined. In this single-center retrospective cohort study we assessed survival including outcomes after hematopoietic stem cell transplant (HSCT) with respect to novel agent exposure.MethodsPatients diagnosed with PTCL from 2012-2017 who consented for inclusion in the Weill Cornell lymphoma and bone marrow transplant databases with adequate treatment records were included. Medical records were reviewed for baseline characteristics, treatment course, and outcomes including overall survival and HSCT. Median follow-up time was estimated on overall survival by reverse Kaplan-Meier method. Overall Survival (OS) time was calculated from date of diagnosis to date of death or last follow-up. Kaplan-Meier estimator was used to estimate survival probability. Survival difference between groups was tested by log-rank test and Cox regression analysis for statistical significance.ResultsA total of 123 cases were reviewed with median follow-up of 34 months. The major PTCL subtypes were PTCL NOS (N=34, 27.6%), angioimmunoblastic T-cell lymphoma (N=21, 17%), adult T-cell leukemia/lymphoma (N=19, 15.4%), and anaplastic large cell lymphoma (N=14, 11.4%). The most common 1st line chemotherapy regimens were CHOP (N=34, 31.5%), EPOCH (N=21, 19.4%), or CHOEP (N=10, 9.3%). Ninety-two patients had relapsed or refractory disease, and the most common 2nd line therapies were DICE/ICE (N=17, 18.4%), gemcitabine-based regimens (N=6, 7.5%), bendamustine (N=5, 5.4%), hyperCVAD (N=5, 5.4%), or combinations of novel agents. Thirty-three R/R patients received a novel agent, including pralatrexate alone (N=3), BV (N=13), or romidepsin (N=17). Thirty-six R/R patients underwent HSCT, including 26 allogeneic and 10 autologous.Baseline characteristics at diagnosis including age, gender, Ann Arbor stage, ECOG status, and IPI were similar between R/R patients who received a novel agent and those who did not. Although no differences in OS were seen with novel agent use among patients with R/R disease, there was a significant difference in OS among patients who received HSCT and those who did not (p=0.012 by log-rank test). Compared to no HSCT, significantly improved survival was observed in patients receiving allogeneic HSCT (HR = 0.47, p = 0.03) as well as autologous HSCT (HR = 0.27, p= 0.03) by Cox regression survival analysis, both univariate and multivariate when adjusting for interaction with novel agents.ConclusionData from this single-center retrospective cohort study suggest that hematopoietic stem cell transplant, both autologous and allogeneic, was associated with overall survival benefit in R/R diseases in the novel agent era. The real world impact of novel agents use in PTCL subtypes warrants further study, preferably in a prospectively designed multicenter population study with larger sample size where disease subtypes, therapeutic targets of novel agents, and line of therapies can be sufficiently delineated for response and survival analysis. DisclosuresMartin:AstraZeneca: Consultancy; Gilead: Consultancy; Bayer: Consultancy; Janssen: Consultancy; Seattle Genetics: Consultancy; Kite: Consultancy. Allan:Acerta: Consultancy; Sunesis: Membership on an entity's Board of Directors or advisory committees; Verastem: Membership on an entity's Board of Directors or advisory committees; AbbVie: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees. Furman:TG Therapeutics: Consultancy; Sunesis: Consultancy; Loxo Oncology: Consultancy; Incyte: Consultancy, Other: DSMB; Gilead: Consultancy; Genentech: Consultancy; Acerta: Consultancy, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; Verastem: Consultancy; Janssen: Consultancy; AbbVie: Consultancy.

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.