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

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

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A Retrospective Analysis on Prognostic Factors of Angioimmunoblastic T-Cell Lymphoma: a Multicenter Cooperative Study In Japan

Blood ◽

10.1182/blood.v116.21.3117.3117 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3117-3117

Author(s):

Takashi Tokunaga ◽

Kazuyuki Shimada ◽

Kazuhito Yamamoto ◽

Dai Chihara ◽

Takuji Ichihashi ◽

...

Keyword(s):

Prognostic Factors ◽

T Cell ◽

Research Funding ◽

Cell Lymphoma ◽

Prognostic Index ◽

T Cell Lymphoma ◽

Rank Test ◽

Angioimmunoblastic T Cell Lymphoma ◽

Log Rank Test ◽

Number Of Patients

Abstract Abstract 3117 Background: Angioimmunoblastic T-cell lymphoma (AITL) is one of the major types of peripheral T-cell lymphoma (PTCL), with T follicular helper cells (TFH) reported to be the normal counterpart cell type. The disease generally presents with poor prognosis following conventional chemotherapy treatments. Furthermore, existing prognostic factors or predictive models for non-Hodgkin lymphoma are not useful in the prognostification of AITL. Identification of novel prognostic factors is therefore vital. Unfortunately, the number of studies using a large cohort of patients with AITL has so far been limited. Patients and Method: To elucidate the clinicopathological characteristics of AITL in Japan, we retrospectively analyzed 213 patients who were diagnosed with AITL between January 1990 and September 2008 from 31 participating hospitals. Patients with AITL were eligible for analysis only if their diagnosis was confirmed by histopathological and immunohistochemical criteria in accordance with the WHO classification. For immunohistochemical analysis, we evaluated CD10, CXCL13, PD-1 and EBER-ISH in addition to routine immunostaining. Clinical data was retrospectively collected from case reports. Patients received treatment for AITL according to the respective institutional protocols. Overall survival (OS) and progression free survival (PFS) were analyzed by using the log-rank test, and results expressed as Kaplan-Meier plots. Cox proportional hazard regression analysis with OS and PFS was performed to identify potential independent prognostic factors. This study was approved by the institutional review board of participating hospitals and complied with the provisions of the Declaration of Helsinki. Result: The median patient age was 67 years (range: 34–89 years), with 74% of patients older than 60 years. The female:male ratio was 1:1.8. Ninety percent of patients displayed Stage III or IV disease, and 23% of patients involved more than 1 extranodal site. B-symptoms and bone marrow involvement were present in 60% and 30% of patients, respectively. Laboratory findings showed anemia (male: Hb <13.0 g/dl, female: Hb <11.0 g/dl) in 61% of patients, a positive Coombs test in 47%, hypergammaglobulinemia (IgG >1700 mg/dl) in 54%, IgA >400 mg/dl in 37%, and elevated serum LDH levels in 75% of patients, respectively. According to the international prognostic index (IPI) and prognostic index for PTCL-NOS (PIT) score, patients were categorized as follows; IPI: Low (L), 10% (22/199); Low-intermediate (LI), 20% (39/199); High-intermediate (HI), 39% (77/199); and High (H), 31% (61/199), respectively, and PIT: Group1 (G1), 4% (8/201); Group2 (G2), 19% (38/201); Group3, 42% (85/201); and Group4, 35% (70/201), respectively. In terms of the initial series of treatments, 84% of patients received anthracycline-based chemotherapies. With a median follow-up duration of 42 months in surviving patients, 3-year OS and PFS were 54% and 39%, respectively. IPI was predictive for OS (3-years OS: L, 84%; LI, 65%; HI, 54%; H, 38%; Log-rank test, p<0.001), however, PIT was less predictive than IPI according to the distribution of the number of patients and survival in each group (3-years OS: G1, 88%; G2, 65%; G3, 57%; G4, 42%; Log-rank, p=0.014). Immunohistochemical staining revealed positivity for CD10 in 31% (40/130), EBER-ISH in 68% (108/160), CXCL13 in 92% (76/83), and PD-1 in 61% of patients (51/83), respectively. Multivariate analysis revealed total protein (TP) (<6.5 g/dl), {hazard ratio (HR), 2.12; 95% confidence interval (CI), 1.20–3.72; p=0.010}, IgA (>400 mg/dl) (HR, 2.00; 95% CI, 1.19–3.34; p=0.009), anemia (male, Hb <13.0 g/dl; female, Hb <11.0 g/dl) (HR, 1.95; 95% CI, 1.11–3.52; p=0.020), CRP (>1.0 mg/dl) (HR, 1.84; 95% CI, 1.05–3.35; p=0.033), and performance status (>2) (HR, 1.73; 95% CI, 1.03–2.92; p=0.040) were identified as significant prognostic factors for OS. IgA (HR, 1.94; 95% CI, 1.25–2.98; p=0.003), and anemia (HR, 1.65; 95% CI, 1.03–2.66; p=0.036) were significant prognostic factors for PFS. Conclusion: Prognosis of patients with AITL in Japan is poor. Although IPI was useful in prognostification of AITL, other factors including those not adopted in IPI, such as IgA, anemia, TP and CRP, significantly affected the prognosis in this analysis. Further validation studies of these criteria should be performed. Disclosures: Naoe: Chugai Pharmaceutical Co.,Ltd.: Research Funding; Zenyaku Kogyo Co.: Research Funding; Kyowa Hakko Kirin Co.,Ltd.: Research Funding; Dainippon Sumitomo Pharma Co.,Ltd.: Research Funding; Novartis Pharma K.K.: Research Funding; Janssen Pharmaceutical K.K.: Research Funding. Kinoshita:Chugai Pharmaceutical Co.,Ltd.: Research Funding; Zenyaku Kogyo Co.: Research Funding; Kyowa Hakko Kirin Co.,Ltd.: Research Funding.

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

Blood ◽

10.1182/blood-2020-134814 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 27-28

Author(s):

Monica Mead ◽

Henrik Cederleuf ◽

Thomas Relander ◽

Mats Jerkeman ◽

Fredrik Ellin ◽

...

Keyword(s):

T Cell ◽

Elderly Patients ◽

Cause Of Death ◽

Research Funding ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Rank Test ◽

Peripheral T Cell Lymphoma ◽

Cutaneous Lymphomas ◽

Ann Arbor

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 > 1 (39 %). Male patients more often had a CCI score > 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 < 0.001). Age > 80 years, CCI > 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 >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 > 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.

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Pralatrexate Is Effective In Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma (PTCL) with Prior Ifosfamide, Carboplatin, and Etoposide (ICE)-Based Regimens

Blood ◽

10.1182/blood.v116.21.1753.1753 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1753-1753 ◽

Cited By ~ 2

Author(s):

Andre Goy ◽

Barbara Pro ◽

Kerry Joanne Savage ◽

Nancy L. Bartlett ◽

Mary Jo Lechowicz ◽

...

Keyword(s):

T Cell ◽

Combination Chemotherapy ◽

Research Funding ◽

Cell Lymphoma ◽

The United States ◽

T Cell Lymphoma ◽

Cell Transplant ◽

Second Line ◽

Peripheral T Cell Lymphoma ◽

Line Therapy

Abstract Abstract 1753 Background: Peripheral T-cell lymphoma (PTCL) is a group of aggressive T- and NK-cell lymphomas with a poor prognosis, with most patients progressing within 6 to 12 months after first-line therapy. Despite a paucity of data in PTCL, combination chemotherapy such as ifosfamide/carboplatin/etoposide (ICE)-based regimens (eg, ICE, rituximab-ICE [RICE] and dexamethasome-ICE [DICE]), are often used in the salvage setting. These regimens can induce responses allowing some patients to proceed to a stem cell transplant (SCT), yet most patients relapse quickly (Horwitz et al, Blood. 2005;(106:a2679; Zelenetz et al Annals Oncol. 2003;14:i5-i10.). Pralatrexate (FOLOTYN®), a rationally-designed folate analog, was granted accelerated approval in the United States for the treatment of relapsed or refractory PTCL, based on results of the pivotal study, PROPEL (Pralatrexate in Patients with Relapsed Or Refractory Peripheral T-cell Lymphoma). The present exploratory analysis of PROPEL data was conducted to assess the efficacy of pralatrexate postfailure of ICE-based regimens. Methods: Of the 109 patients enrolled in PROPEL and evaluable for efficacy, a subset of 20 patients had received an ICE-based regimen as their second-line therapy and progressed at some point prior to treatment with pralatrexate (30 mg/m2 weekly for 6 of 7 week cycles). Results: The median age of the 20 patients with a prior ICE-based regimen was 45 years. A summary of pralatrexate efficacy data is presented in the table below. Pralatrexate demonstrated ORR of 40% in ICE-pretreated patients (n=20). Nine of the 20 patients received ICE-based regimens as their most recent therapy prior to pralatrexate. Of these, 2 patients did not respond to these aggressive combination chemotherapies, but did respond to pralatrexate (1 CR and 1 PR). Two of the 20 patients achieved a CR on pralatrexate and proceeded to SCT; DoR to pralatrexate in these patients was censored (at 1.3 and 4.9 months). However, these 2 patients remain in CR and the current disease-free period (DoR: pralatrexate + transplant) is 10.9 and 30.8 months. The most common grade 3 adverse events (AEs) were anemia (8 patients) and mucositis (5 patients), and grade 4 AEs was thrombocytopenia (6 patients). Five patients discontinued treatment with pralatrexate due to AEs. From a safety perspective, this compares favorably with ICE-based regimens, recognized for their intensity and their need for hospitalization for administration (Hertzberg et al, Ann Oncol. 2003;14[suppl 1] i11-i16). The PROPEL study also collected information on response to therapies administered prior to study entry. In the 20 patients included in the analysis, the ORR to prior ICE-based regimens was 25% with 3 patients achieving CR (15%) and 2 PR (10%). An additional 3 patients had SD (15%), 7 had PD (35%), and 5 patients had nonassessable response. The median duration on treatment for responders to ICE-based regimens was <1 month, in contrast with pralatrexate's long DoR (median 16.2 months according to investigators’ assessment). Conclusions Pralatrexate was highly active in patients with PTCL who received prior ICE-based chemotherapy, with an ORR of 40% including CRs leading to SCT in some patients. Of note, is the long duration of pralatrexate responses in marked contrast to the short response duration of the combination chemotherapy regimens. Taken together, the efficacy of single-agent pralatrexate compared favorably with ICE-based regimens, a finding that is consistent with other exploratory analyses, showing that pralatrexate can reverse the characteristic progressive resistance of PTCL patients to second-line chemotherapy, and that pralatrexate is an effective second-line treatment for patients with PTCL. Disclosures: Goy: Allos Therapeutics, Inc.: Consultancy, Honoraria. Pro:Allos Therapeutics, Inc. : Research Funding. Savage:Allos Therapeutics, Inc.: Consultancy, Honoraria. Lechowicz:Allos Therapeutics, Inc.: Consultancy; Celgene Corporation: Consultancy. Jacobsen:Allos Therapeutics, Inc.: Consultancy. Fruchtman:Allos Therapeutics, Inc.: Employment. O'Connor:Allos Therapeutics, Inc.: Research Funding.

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Phase I Study of Yttrium-90 Labeled ANTI-CD25 (aTac) Monoclonal Antibody PLUS BEAM for Autologous Hematopoietic CELL Transplantation (AHCT) in Patients with Mature T-CELL NON-Hodgkin Lymphoma, the "a-TAC-BEAM Regimen"

Blood ◽

10.1182/blood-2018-99-116907 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 611-611 ◽

Cited By ~ 1

Author(s):

Jasmine Zain ◽

Jennifer Simpson ◽

Joycelynne Palmer ◽

Jeffrey Wong ◽

Savita Dandapani ◽

...

Keyword(s):

Monoclonal Antibody ◽

T Cell ◽

Research Funding ◽

Cell Lymphoma ◽

Conditioning Regimen ◽

T Cell Lymphoma ◽

High Dose ◽

Hematologic Toxicity ◽

Cell Transplant ◽

Yttrium 90

Abstract Background: Peripheral T cell lymphomas (PTCL) have a poor prognosis with current treatment regimens. High-dose chemotherapy followed by autologous stem cell transplant (ASCT) has been used as a consolidation strategy in remission states (CR1 or above) endorsed by the NCCN guidelines in appropriate patients. 5 year DFS is reported at 70% for alk -ve anaplastic large cell lymphoma (ALCL) and 30-40% for most other histologies (D'Amore et al, 2012, JCO). It is also performed in the relapsed settings if no previous ASCT performed and allogeneic transplant is not an option. CD25 is a targetable protein expressed differentially in PTCL and antibody based anti-CD25 therapies are efficacious in PTCL i.e denileukin diftitox (Foss et al Blood 2006, Dang et al , BJH 2006) , monoclonal antibody dacluzimab (Waldman et al 1995 Blood). Yttrium-90 (90Y) labeled chimeric antiCD25 antibody basiliximab emits beta particles and has been shown to inhibit the growth of human ALCL tumors and increase survival in SUDHL-1 xenograft mice (Zhang et al 2009 Cancer Biother Radiopharm). Previous investigations at COH by Raubitschek, Colcher et al established a safe does of Yttrium-90 (90Y) labeled basiliximab at 0.4mCi/kg in combination with BEAM. This is a phase 1 clinical trial of a novel conditioning regimen that includes the use of Yttrium-90 (90Y) labeled basiliximab with BEAM chemotherapy for PTCL patients eligible for ASCT. The trial utilizes a modified version of the rolling 6 design (Skolnik et al) to test 3 dose levels of Yttrium-90 (90Y) Basiliximab i.e 0.4mCi/kg, 0.5miC/kg and 0.6mCi/kg with the primary objective of evaluating the safety and tolerability of this combination and to establish the MTD. Secondary objectives include incidence of relapse, OS, PFS, NRM at day 100, 1 year and 2 years post-transplant. Patients and Methods: Dose limiting toxicity (DLT) is defined according to the Bearman and CTCAE 4.03 scales, the latter for hematologic toxicity. The study/treatment schema is shown in Figure 1. Results: From 07/29/2015 to 05/29/2018, 14 patients underwent ASCT on this trial; n=4 at 0.4mCi/kg n=4 at 0.5mCi/kg and n=6 at 0.6mCi/kg. Median age at ASCT was 51 years (range: 18-76), and histologies included; PTCL-nos (n=7); alk-ve ALCL (n=3); angioimmunoblastic T-cell lymphoma (n=2); and intestinal T-cell lymphoma (n=2). Disease status at ASCT were CR1 in12, CR2 in 2 patients. Median number of prior therapies was 1 (range: 1-2). At a median follow-up of 14.4 months (range: 0.9-26.2), 8 patients remain in remission, 4 have relapsed out of which 2 have died of progressive lymphoma. OS was 100% (95% CI: N/A) at 100-days, and89% (95% CI: 43-98) at 1 year. Non-relapse Mortality was 0% at both100-days and 1-year (95%CI: N/A) (95%CI: N/A). All patients successfully engrafted with the median days to ANC >= 500/ul was 11 (range: 10 - 12), and days to PLT >= 20,000/ul: 13 (12 - 92). No dose limiting toxicities were experienced. The most common/highest grade toxicity experienced (per Bearman Scale) was grade 2 stomatitis, which was seen in 3 patients at 0.4mCi/kg; 4 patients at 0.5 mCi/kg, and 3 at0.6mCi/kg. The only other toxicities seen were grade 2 GI in 2 patients at 0.4mCi/kg,and grade 2 bladder in one patient at 0.6mCi/kg dose.. Toxicities >grade 2 were not seen. Conclusion: aTac- BEAM appears to be safe as an ASCT conditioning regimen for PTCL with no increased toxicity as compared to the historical toxicities seen with BEAM alone in this patient population (D'Amore 2012 J of Clin Onc). The dose level 0.6mCi/kg will likely be the recommended phase II dose. An expanded phase is planned to evaluate the efficacy of this regimen followed by a randomized trial of BEAM alone plus a combination of aTac- BEAM. Figure 1. Figure 1. Disclosures Herrera: Seattle Genetics: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; Immune Design: Research Funding; KiTE Pharma: Consultancy, Research Funding; Merck, Inc.: Consultancy, Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Research Funding; Gilead Sciences: Research Funding. Salhotra:Kadmon Corporation, LLC: Consultancy.

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

Blood ◽

10.1182/blood-2021-148038 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1381-1381

Author(s):

Frederik O. Meeuwes ◽

Mirian Brink ◽

Marjolein W.M. Van Der Poel ◽

Marie José Kersten ◽

Mariëlle Wondergem ◽

...

Keyword(s):

T Cell ◽

The Netherlands ◽

Research Funding ◽

Cell Lymphoma ◽

Population Based ◽

T Cell Lymphoma ◽

Stage I ◽

Advanced Stage ◽

Limited Stage ◽

Stage Disease

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

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TP53 Mutations Identify High-Risk Peripheral T-Cell Lymphoma Patients Treated with CHOP-Based Chemotherapy

Blood ◽

10.1182/blood-2021-151779 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 1367-1367

Author(s):

William T. Johnson ◽

Nivetha Ganesan ◽

Zachary D. Epstein-Peterson ◽

Catherine Maccaro ◽

Natasha Galasso ◽

...

Keyword(s):

T Cell ◽

Prospective Cohort ◽

Research Funding ◽

Cell Lymphoma ◽

Genetic Alterations ◽

T Cell Lymphoma ◽

Cell Transplant ◽

Peripheral T Cell Lymphoma ◽

Entire Cohort ◽

Mutational Profiling

Abstract Introduction Mutational profiling in peripheral T-cell lymphoma (PTCL) is increasingly used to aid in diagnosis (Wang. Blood 2015), predicting response (Ghione. Blood Adv 2020), and prognosis (Watatani. Leukemia 2019). However, many analyses lack details of upfront treatment and survival outcomes. The Memorial Sloan Kettering Integrated Mutation Profiling of Actionable Cancer Targets (MSK-IMPACT) is a custom hybridization capture-based assay encompassing the protein-coding exons of >400 targeted genes (Cheng. J Molec Diag 2015). Using the MSK-IMPACT data generated from a large TCL patient (pt) population (N=396), we sought alterations which may predict resistance to or high rates of relapse after CHOP-based chemotherapy. Methods PTCL pts with MSK-IMPACT were detected in the CBioPortal online platform. We included histologies treated with curative intent CHOP-based induction +/- autologous stem cell transplant (ASCT). This included PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AITL), PTCL with a T-follicular helper phenotype (FH-TCL), ALK+ and ALK- anaplastic large cell lymphoma (ALCL), and monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL). Univariate analysis (UVA) for PFS and OS based on the presence of recurring genetic alterations was done using Cox proportional hazard regression analysis. Mutations (mut) assessed included TET2, DNMT3A, RHOA, IDH2, TP53, FAT1, STAT3, STAT5B, JAK1, SETD2, and copy number alterations (CNA) in TP53 and CDKN2A. Comparisons of survival curves were performed by log-rank test. As many pts were sequenced at relapse, to minimize bias, relevant findings were confirmed in the smaller set of pts sequenced at diagnosis and/or before relapse (prospective cohort). Results In total, 131 pts met inclusion criteria and had >1 MSK-IMPACT. One pt with a 49-gene panel was also included (N=132). The prospective cohort had 73 (55%) pts. Histologies were PTCL-NOS (N=36, 27%), AITL (N=62, 47%), FH-TCL (N=9, 7%), ALK-ALCL (N=15, 11%), ALK+ALCL (N=6, 5%), and MEITL (N=4, 3%). Regimens were CHOP + etoposide (N=59, 45%), CHOP (N=40, 30%), brentuximab + CHP (N=15, 11%), other CHOP-based (N=18, 14%). The most frequent mut were TET2 (N=69, 52%), RHOA (N=40, 30%), DNMT3A (N=25, 19%), TP53 (N=21, 16%), and IDH2 (N=15, 11%), and for CNA were losses of TP53 (N=9, 7%) and CDKN2A (N=9, 7%). TET2 mut were most frequent in AITL (N=51, 82%), FH-TCL (N=6, 67%), and PTCL-NOS (N=10, 28%). RHOA mut were found in 2 cases of PTCL-NOS (6%) with the rest in AITL (N=33, 53%) and FH-TCL (N=5, 56%). DNMT3A mut were most frequent in AITL (N=19, 31%) and FH-TCL (N=4, 44%). IDH2 mut were exclusive to AITL (N=14, 23%) and FH-TCL (N=1, 11%). TP53 mut were found in all histologies: ALK-ALCL (N=5, 33%), PTCL-NOS (N=10, 28%), FH-TCL (N=2, 22%), AITL (N=2, 3%), and in one case each of ALK+ALCL (17%) and MEITL (25%). The 24-month PFS was 28% for the entire cohort, and 42% for the prospective cohort. On UVA for genetic alterations, only TP53 mut (P=0.0011) and TP53 deletions (P=0.009) associated with inferior PFS. On MVA, only TP53 mut remained significant (HR 2.0 [95% CI 1.1-3.5] P=0.02). No alteration associated with inferior OS. For the entire cohort, median PFS was 4.5 mos for TP53 mut (N=21) vs. 10.5 mos for TP53 wild-type (WT) (N=111) (log-rank P=0.0008). This was similar in the prospective cohort with a median PFS of 4.1 vs. 19.7 mos (log-rank P=0.02) (Figure 1). Compared to TP53 WT, TP53 mut were more likely to have PTCL-NOS (P=0.03), concurrent deletions of TP53 (P=0.0005), and a higher median number of alterations (P=0.01). There were no differences in age, stage, marrow disease, or IPI/PIT scores between TP53 mut and TP53 WT pts. There was a trend towards fewer CR (P=0.054) in TP53 mut. There were no differences in ITT with ASCT between the groups (P=0.5). This was similar in the prospective cohort (P=0.4). Six total (29%) TP53 mut received ASCT, and PFS was similar to ASCT in TP53 WT (median 18.2 vs. 19.7 mos, P=0.5), but 5/6 (83%) ultimately relapsed. Conclusions TP53 mut correlated with lower rates of CR, higher rates of relapse, and shorter PFS in this dataset of PTCL treated with CHOP-based chemotherapy. OS was not different compared to TP53 WT tumors. The confounding impact of histology and other prognostic factors as well as the lack of uniform prospective mutational profiling in this retrospective series precludes definitive conclusions and requires prospective confirmation. Figure 1 Figure 1. Disclosures Sauter: Juno Therapeutics: Consultancy, Research Funding; Sanofi-Genzyme: Consultancy, Research Funding; Spectrum Pharmaceuticals: Consultancy; Novartis: Consultancy; Genmab: Consultancy; Precision Biosciences: Consultancy; Kite/Gilead: Consultancy; Celgene: Consultancy, Research Funding; Gamida Cell: Consultancy; GSK: Consultancy; Bristol-Myers Squibb: Research Funding. Khan: Seattle Genetics: Research Funding. Moskowitz: ADC Therapeutics: Research Funding; Beigene: Research Funding; Seattle Genetics: Consultancy, Research Funding; Miragen: Research Funding; Bristol-Myers Squibb: Research Funding; Merck: Consultancy, Research Funding; Janpix Ltd.: Consultancy; Imbrium Therapeutics L.P./Purdue: Consultancy; Takeda: Consultancy; Incyte: Research Funding. Dogan: Seattle Genetics: Consultancy; Roche: Consultancy, Research Funding; Peer View: Honoraria; EUSA Pharma: Consultancy; Takeda: Consultancy, Research Funding; Physicians' Education Resource: Honoraria. Horwitz: ADC Therapeutics: Consultancy, Research Funding; Acrotech Biopharma: Consultancy; Affimed: Research Funding; Aileron: Research Funding; Celgene: Research Funding; C4 Therapeutics: Consultancy; Daiichi Sankyo: Research Funding; Forty Seven, Inc.: Research Funding; Kyowa Hakko Kirin: Consultancy, Research Funding; Janssen: Consultancy; Kura Oncology: Consultancy; Millennium /Takeda: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Trillium Therapeutics: Consultancy, Research Funding; SecuraBio: Consultancy, Research Funding; Myeloid Therapeutics: Consultancy; ONO Pharmaceuticals: Consultancy; Shoreline Biosciences, Inc.: Consultancy; Tubulis: Consultancy; Vividion Therapeutics: Consultancy; Verastem: Research Funding.

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Stem Cell Transplant (SCT) and Pralatrexate Therapy: Outcome of Patients with Relapsed or Refractory Peripheral T-Cell Lymphoma Who Received SCT Prior to or Following Pralatrexate Therapy.

Blood ◽

10.1182/blood.v114.22.3420.3420 ◽

2009 ◽

Vol 114 (22) ◽

pp. 3420-3420

Author(s):

Leslie Popplewell ◽

Barbara Pro ◽

Eric Jacobsen ◽

Steven M. Horwitz ◽

Adam Boyd ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Research Funding ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Cell Transplant ◽

Peripheral T Cell Lymphoma ◽

Additional Therapy

Abstract Abstract 3420 Poster Board III-308 Background Stem cell transplant (SCT) may be offered as a curative approach in patients with chemotherapy-sensitive peripheral T-cell lymphoma (PTCL). Thus, new agents with the ability to induce a response for relapsed or refractory patients are important to identify. This analysis evaluated SCT use before or after pralatrexate, a new anti-folate, as monotherapy in the PROPEL study. Methods Patients with relapsed or refractory PTCL received pralatrexate 30 mg/m2 by IV push once weekly for 6 weeks in 7-week cycles with vitamin B12 and folic acid supplementation in PROPEL. Eligibility criteria included histologic confirmation of PTCL by central review, disease progression after ≥ 1 prior treatment, and ECOG performance status £ 2. Response was assessed centrally using the International Workshop Criteria. Patients who had received prior allogeneic SCT were not permitted to enroll. Patients with prior autologous SCT were eligible if they had not relapsed within 75 days of SCT. There were no restrictions on SCT after completing study treatment. Subsequent post-pralatrexate therapies were recorded during follow up until patient death, loss to follow-up, or data cutoff. Results One-hundred and nine patients in the PROPEL trial were evaluable for response. Eighteen (16%) had received autologous SCT previously, including 8 (7%) patients for whom SCT was the most recent therapy prior to study enrollment. The overall response rate (ORR: complete response [CR/CRu] or partial response [PR]) was 33% (6/18), including 2 CRs, for patients with a prior autologous SCT at any time prior to receiving pralatrexate and 63% (5/8), including 2 CRs, for those patients whose most recent therapy was autologous SCT. Patients were followed from initiation of pralatrexate for a median of 10.5 months (range, 1.0-24.0). Of the 109 patients who were evaluable for response, 6 (6%) patients went on to SCT (2 autologous SCT, 4 allogeneic SCT) as their initial subsequent therapy after responding to pralatrexate according to investigator assessment of response. Four of these patients were still in response by central review at the time they started SCT. At the time of data cutoff, no additional therapy was administered to any of these 4 patients post SCT. The other 2 patients had PRs by investigator review and progressive disease by central review at the time SCT was started; neither of these patients had additional therapy documented after SCT. All 6 patients were alive at the time of last contact. Conclusions The PROPEL trial showed that pralatrexate as a single agent had activity, including CRs, in patients who relapsed following an autologous SCT. The PROPEL trial also demonstrated that patients with relapsed or refractory PTCL can proceed to subsequent SCT after achieving a response with pralatrexate, permitting these patients a transplant option and potential cure. Disclosures Pro: Allos Therapeutics, Inc.: Research Funding. Jacobsen:Allos Therapeutics, Inc.: Consultancy. Horwitz:Allos Therapeutics, Inc: Consultancy, Research Funding. Boyd:Allos Therapeutics, Inc.: Employment. Fruchtman:Allos Therapeutics, Inc.: Employment.

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Use of multigeneration-family molecular dog leukocyte antigen typing to select a hematopoietic cell transplant donor for a dog with T-cell lymphoma

Journal of the American Veterinary Medical Association ◽

10.2460/javma.228.5.728 ◽

2006 ◽

Vol 228 (5) ◽

pp. 728-732 ◽

Cited By ~ 16

Author(s):

Marilena Lupu ◽

Edmund W. Sullivan ◽

Theresa E. Westfall ◽

Marie-Térèse Little ◽

Benjamin J. Weigler ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

Hematopoietic Cell ◽

T Cell Lymphoma ◽

Cell Transplant ◽

Hematopoietic Cell Transplant ◽

Leukocyte Antigen

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Higher Titer of Anti-EBV Nuclear Antigen Antibodies Might be a Marker of Poorer Prognosis in Patients with Peripheral T-Cell Lymphoma, Not Otherwise Specified

Blood ◽

10.1182/blood.v126.23.5016.5016 ◽

2015 ◽

Vol 126 (23) ◽

pp. 5016-5016

Author(s):

Yoshiharu Kusano ◽

Yasuhito Terui ◽

Kyoko Ueda ◽

Yuko Mishima ◽

Noriko Nishimura ◽

...

Keyword(s):

T Cell ◽

Response Rate ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Nuclear Antigen ◽

Rank Test ◽

P Value ◽

Not Otherwise Specified ◽

Log Rank Test ◽

Therapeutic Outcomes

Abstract Background Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA) is the only viral protein consistently expressed by EBV. Anti-EBNA-1 antibodies (EBNA-Ab) status has long been the method to diagnose the latent EBV infection to date. Both positivity of EBV-encoded small RNA in situ hybridization using lymph node and positivity of EBV-DNA using peripheral blood meant that poor therapeutic outcomes in patients with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS) and with NK/T-cell lymphoma, respectively. It has been unknown whether EBNA-Ab status has another clinical implication except knowing latent EBV infection. Methods This is an observational trial in single cancer institute. EBNA-Ab has routinely measured before the treatment in patients with PTCL-NOS, who were diagnosed or treated in our hospital from July 2001 to December 2014. Then, we analyzed that whether these patients attributed their therapeutic outcomes to the each value of their pretreatment EBNA-Ab titer. Primary objective was to evaluate a prognostic value of EBNA-Ab titer for one-year overall survival (OS). Secondary objective was response rate. Results In total of 30 cases, 24 showed EBNA-Ab positive (titer ≥ 10). Baseline patients characteristics run as follows; median age was 63 (26-83), 22 were men, 18 were Ann Arbor stage ≥ 3, 11 were IPI ≥ 3, 9 showed elevated LDH. All patients were given six cycles of CHOP except one patient (CHOEP). Overall response rate (ORR) was 40% and complete response rate (CRR) was 27%. 40% showed progression disease. The median OS was 51.4 months. At the median follow-up of 12 months, the pretreatment EBNA-Ab level demonstrated significant correlation with prognosis. OS was 52.7% (95% confidential index [CI]: 30-71) and 100% (95%CI: 100-100) in cases that EBNA-Ab positive and EBNA-Ab negative, respectively (Figure 1, p value of log-rank test = 0.013). Furthermore, we compared outcomes in the three groups: EBNA-Ab < 10, 10 ≤ EBNA-Ab ≤ 60, and EBNA-Ab > 60. Each group has same proportion of age > 60 (p value of fisher exact test = 0.26), sex (p = 0.51), IPI ≥ 3 (p = 0.85), stage ≥ 3 (p = 0.09), and elevated LDH (p = 0.64). ORR was 33% vs. 44% vs. 33% and CRR was 33% vs. 28% vs. 17% in cases that EBNA-Ab < 10, 10 ≤ EBNA-Ab ≤ 60, and EBNA-Ab > 60. In terms of OS, 100%, 63%, and 20% in cases that EBNA-Ab < 10, 10 ≤ EBNA-Ab ≤ 60, and EBNA-Ab > 60, respectively (Figure 2, p value of log-rank test = 0.0007). Conclusion As these results demonstrated, in this study, patients with high-level titer of EBNA-Ab demonstrated shorter OS. Especially, EBNA-Ab titer > 60 cases showed the worst outcome. By contrast, EBNA-Ab negativity demonstrated significantly longer OS. Higher EBNA-Ab might be an independent marker that associated with poorer outcomes in patients with PTCL-NOS. Figure 1. OS between EBNA-Ab < 10 and ≥ 10 arms (p = 0.01) Figure 1. OS between EBNA-Ab < 10 and ≥ 10 arms (p = 0.01) Figure 2. OS between EBNA-Ab < 10, 10 ≤ EBNA-Ab ≤ 60, and EBNA-Ab > 60 arms (p = 0.0007) Figure 2. OS between EBNA-Ab < 10, 10 ≤ EBNA-Ab ≤ 60, and EBNA-Ab > 60 arms (p = 0.0007) Disclosures Mishima: Chugai Pharmaceutical CO., LTD.: Consultancy. Nishimura:Chugai Pharmaceutical CO., LTD.: Consultancy. Yokoyama:Chugai Pharmaceutical CO., LTD.: Consultancy. Hatake:Chugai Pharmaceutical CO., LTD.: Other: lecture speaking.

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An International Assessment of Event-Free Survival at 24 Months (EFS24) and Subsequent Survival in Peripheral T-Cell Lymphoma

Blood ◽

10.1182/blood.v128.22.920.920 ◽

2016 ◽

Vol 128 (22) ◽

pp. 920-920

Author(s):

Matthew J Maurer ◽

Fredrik Ellin ◽

Line Srour ◽

Mats Jerkeman ◽

Nabila Nora Bennani ◽

...

Keyword(s):

T Cell ◽

Research Funding ◽

Stem Cell Transplant ◽

Cell Lymphoma ◽

Autologous Stem Cell Transplant ◽

T Cell Lymphoma ◽

Cell Transplant ◽

Event Free Survival ◽

Free Survival ◽

First Remission

Abstract Background: Peripheral T-cell lymphomas (PTCLs) comprise a group of non-Hodgkin lymphomas (NHLs) of mature T-cell origin with generally aggressive clinical behavior. Most systemic PTCLs are treated with anthracycline-based combination chemotherapy; however, outcomes remain relatively poor for most subtypes except ALK-positive anaplastic large cell lymphoma (ALCL). We have used landmark analyses based on event-free survival (EFS) to identify clinically useful endpoints in B-cell NHLs, with EFS at 24 (EFS24) months identified to stratify overall survival (OS) in aggressive B-cell NHL. Here we examined the ability of EFS24 to predict subsequent OS in a large, multinational PTCL cohort. Methods: A cohort of newly diagnosed PTCL patients treated with curative intent combination chemotherapy regimens was assembled from the University of Iowa/Mayo Clinic SPORE Molecular Epidemiology Resource (MER), Swedish Lymphoma Registry (SWE), and British Columbia Cancer Agency (BCCA). Subtypes included ALK-negative ALCL, angioimmunoblastic T-cell lymphoma (AITL), PTCL, not otherwise specified (NOS), enteropathy-associated T-cell lymphoma (EATL), extranodal NK/T-cell lymphoma, nasal type (ENKTL), and hepatosplenic T-cell lymphoma (HSTCL). Patients were followed based on local institution guidelines, and EFS was defined as time from the date of pathologic diagnosis to progression, re-treatment, or death due to any cause. EFS24 was defined as being alive and event-free 24 months from diagnosis. Subsequent OS was defined as time from achieving EFS24 (24 months from diagnosis) or time from progression in patients failing to achieve EFS24 (progression within 24 months of diagnosis). OS was compared to the age-, sex-, and country-matched general population using United States, Sweden, and British Columbia rate tables via standardized mortality ratios (SMR) and expected survival. Results: 775 patients diagnosed from 2000-2012 were included in the combined analysis with diagnosis by the WHO classification at the respective institutions (MER=138, SWE=422, BCCA=215). Median age at diagnosis was 64 years (range 18-89) and 63% were male. Patient characteristics are summarized in the table. 736 (95%) received anthracyline-based therapy at diagnosis. At a median follow-up of 77 months (range 1-185), 516 patients (67%) had died. The percentage of patients achieving EFS24 was similar across the 3 cohorts (MER=39%, SWE=35%, BCCA= 36%, combined=36%). Median survival after progression within the first 24 months was only 4.9 months (95% CI: 3.8-5.9), with a 5-year OS of 11% and SMR of 46.4 (95% CI: 41.8-51.3). In contrast, median survival after achieving EFS24 was not reached, with a 5-year OS of 78% (95% CI: 73%-84%). This was inferior to the expected survival of 92% in the age-, sex-, and country matched population (SMR=3.16; 95% CI: 2.48-3.98). In EFS24 subgroup analyses, more favorable outcomes were observed in younger patients (age <=60 years, N=137, 5-year survival of 91% vs. 98% expected) and in patients receiving autologous stem cell transplant in first remission (N=72, 5-year survival of 88% vs. 96% expected). Patients achieving EFS24 who were not transplanted in first remission (N=189) had a 5-year survival of 74% vs. 90% expected. Conclusions: Assessment of EFS24 stratifies subsequent outcome in PTCL. Patients with early relapse from PTCL have extremely poor outcomes. However, over one-third of patients with PTCL remain in remission two years from diagnosis after initial chemotherapy and have encouraging OS rates, although survival remains significantly worse than the matched general population. Subset analysis suggests that younger patients and patients who receive autologous stem-cell transplant in first CR have 5-year survival rates that approach 90%, though still below the expected survival of the background population. The marked differences in OS after failing or achieving EFS24 in PTCL patients suggest that this endpoint may be useful for patient counseling, as a clinical trial endpoint, and as an endpoint to assess novel biomarkers for risk stratification. Table Table. Figure 1. Figure 1. Figure 2. Figure 2. Disclosures Maurer: Celgene: Research Funding; Kite Pharma: Research Funding. Jerkeman:Mundipharma: Research Funding; Amgen: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Celgene: Research Funding. Connors:Seattle Genetics: Research Funding; Millennium Takeda: Research Funding; NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Bristol Myers Squib: Research Funding. Ansell:BMS, Seattle Genetics, Merck, Celldex and Affimed: Research Funding.

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