scholarly journals Autologous Stem Cell Transplantation in First Complete Remission May Not Extend Progression Free Survival in Patients with ALK-Negative Peripheral T Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3183-3183 ◽  
Author(s):  
Clinton Yam ◽  
Daniel J. Landsburg ◽  
Xinyi Lin ◽  
Anthony Mato ◽  
Jakub Svoboda ◽  
...  
Keyword(s):  
T Cell ◽  
Induction Chemotherapy ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Primary Therapy ◽  
Free Survival

Abstract Background: Peripheral T cell lymphoma (PTCL) is associated with a poor prognosis when treated with conventional front-line chemotherapy. Although consolidative autologous stem cell transplantation (ASCT) has been reported to improve progression free survival (PFS) when compared to historical controls, there is limited data comparing outcomes in PTCL patients undergoing ASCT versus active observation (AO) in first complete remission (CR1) following CHOP-based induction chemotherapy. Here we compare outcomes in this population at a single institution. Methods: We conducted a retrospective cohort study of PTCL patients treated from 1/1/2007-12/31/2014 and collected data through 7/1/2015. Patients with ALK+ anaplastic large cell lymphoma and cutaneous T cell lymphoma were censored from this analysis. Response to induction chemotherapy was verified through a review of clinical notes and, where available, relevant imaging studies. Therapy was given at the discretion of the treating physician. Our primary outcome measure was PFS, defined as the time from diagnosis to relapse or most recent follow up. Kaplan Meier survival analysis and the log rank test were used to compare outcomes between patients who underwent consolidative ASCT versus those who initiated AO. Results: We identified 105 PTCL patients who received a CHOP-based regimen as first line therapy. 52.4% (55/105) achieved CR1. Of these, 28 initiated AO, 20 underwent consolidative ASCT, 3 underwent consolidative radiation, 1 initiated weekly methotrexate and 3 were lost to follow up. There were no statistically significant differences in age, distribution of PTCL subtypes, IPI scores, stage, B symptoms, LDH, ECOG performance status and choice of primary therapy between the AO group and the ASCT group (Table 1). 28.6% (8/28) and 30.0% (6/20) of patients received etoposide as part of primary therapy in the AO and ASCT group respectively. After a median follow up duration of 22 months, median PFS for the AO and ASCT groups were 15.8 months (95% CI 7.8-23.7) and 12.8 months (95% CI 0-34.0) respectively (Figure 1, p=0.72). Conclusion: In this study, consolidative ASCT was not associated with significantly improved PFS as compared to observation alone for PTCL patients achieving CR1 following CHOP-based induction chemotherapy. Our institutional experience highlights the poor prognosis of patients with PTCL despite an excellent initial response to cytotoxic chemotherapy. With that in mind, novel approaches, including the use of non-cytotoxic agents as part of first-line or consolidative therapy, should be considered in the context of a clinical trial. Table 1. Baseline characteristics and choice of primary therapy AO (n=28) ASCT (n=20) P value Median age - years (range) 61.9 (32.8-78.3) 56.9 (21.4-71.9) 0.07 PTCL subtype PTCL NOS1 - no. (%) 16 (57.1) 6 (30.0) 0.41 AITL2 - no. (%) 5 (17.9) 6 (30.0) ALK- ALCL3 - no. (%) 5 (17.9) 3 (15.0) EATL4 - no. (%) 0 1 (5.0) ATLL5 - no. (%) 1 (3.6) 0 HSTCL6 - no. (%) 1 (3.6) 1 (5.0) Unknown - no. (%) 0 3 (15.0) IPI score at diagnosis 0-1 - no. (%) 5 (17.9) 3 (15.0) 1.00 2-3 - no.(%) 13 (46.4) 10 (50.0) 4-5 - no. (%) 3 (10.7) 2 (10.0) Unknown - no. (%) 7 (25.0) 5 (25.0) Stage at diagnosis I/II - no. (%) 7 (25.0) 4 (20.0) 0.73 III/IV - no. (%) 19 (67.9) 16 (80.0) Unknown - no. (%) 2 (7.1) 0 B symptoms at diagnosis Yes - no. (%) 17 (60.7) 13 (65.0) 1.00 No - no. (%) 9 (32.1) 7 (35.0) Unknown - no. (%) 2 (7.1) 0 LDH at diagnosis Elevated - no. (%) 12 (42.9) 11 (55.0) 0.46 Not elevated - no. (%) 7 (25.0) 3 (15.0) Unknown - no. (%) 9 (32.1) 6 (30.0) ECOG PS at diagnosis 0-1 - no. (%) 17 (60.7) 17 (85.0) 0.26 ≥2 - no. (%) 7 (25.0) 2 (10.0) Unknown - no. (%) 4 (14.3) 1 (5.0) Primary therapy CHOP - no. (%) 18 (64.3) 13 (65.0) 0.82 CHOP/Etoposide - no. (%) 7 (25.0) 6 (30.0) Other - no. (%) 3 (10.7)7 1 (5.0)8 1Peripheral T Cell Lymphoma, Not Otherwise Specified; 2Angioimmunoblastic T Cell Lymphoma; 3ALK negative Anaplastic Large Cell Lymphoma; 4Enteropathy Associated T Cell Lymphoma; 5Adult T Cell Leukemia/Lymphoma; 6Hepatosplenic T Cell Lymphoma; 72 patients received HyperCVAD and 1 patient received HyperCVED; 81 patient received CHOP alternating with DHAP Disclosures Mato: AbbVie: Consultancy, Research Funding; TG Therapeutics: Research Funding; Gilead: Consultancy, Research Funding; Pronai Pharmaceuticals: Research Funding; Genentech: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy, Research Funding; Celgene Corporation: Consultancy, Research Funding. Svoboda:Celgene: Research Funding; Immunomedics: Research Funding; Celldex: Research Funding; Seattle Genetics: Research Funding. Loren:Merck: Research Funding. Frey:Novartis: Research Funding. Porter:Novartis: Other: IP interest, Research Funding; Genentech: Other: Spouse employment. Schuster:Genentech: Consultancy; Pharmacyclics: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Hoffman-LaRoche: Research Funding; Janssen: Research Funding; Gilead: Research Funding; Nordic Nanovector: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding.

Outcome of Patients with Peripheral T-Cell Lymphoma Undergoing Allogeneic Stem Cell in British Columbia

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 5852-5852
Author(s):  
Musa Alzahrani ◽  
Kerry J Savage ◽  
Cynthia L. Toze ◽  
Laurie H Sehn ◽  
Raewyn Broady ◽  
...  
Keyword(s):  
British Columbia ◽  
T Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Primary Therapy ◽  
Peripheral T Cell Lymphoma ◽  
Free Survival ◽  
Kaplan Meier

Abstract Background: Peripheral T-cell lymphomas (PTCL) are a rare and heterogeneous group of non-Hodgkin lymphomas (NHLs) that accounts for approximately 10% of all aggressive NHLs in Western countries. The optimal management remains unclear, however, given the poor outcome, allogeneic transplant (allo-SCT) has been integrated into the front-line treatment for some rare extranodal subtypes as well in relapsed/refractory setting. We report our provincial experience of the outcome of patients with PTCL who have undergone allo-SCT at the British Columbia Cancer Agency (BCCA). Methods: The Leukemia/BMT Program of British Columbia database and the BCCA Lymphoid Cancer Database were searched to identify all patients diagnosed with PTCL who have undergone allo-SCT between November 1990 and January 2016. Overall survival and relapse free survival were estimated using the Kaplan-Meier method. Results: We identified 36 cases of PTCL patients who have undergone allogeneic transplant from a median time of 11 months from primary diagnosis (range 4-64) with the following clinical features: median age at transplant was 45 years (range 16-58 years); 24 (67%) were male; 32 (89%) patients had advanced stage disease; 22 (61%) had B-symptoms at diagnosis. Bone marrow involvement detected in 13/34 (38%) patients. Histological diagnosis based on the WHO 2008 classification were: Peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) n=15 (42%); anaplastic large cell lymphoma (ALCL) n=7 (19%) out of which three were ALK positive, angioimmunoblastic T-cell lymphoma (AITL) n=6 (17%), hepatosplenic T-cell lymphoma n=5 (14%), enteropathy associated T-cell lymphoma type I n=1, advanced primary cutaneous gamma-delta T-cell lymphoma n=1 and Sezary syndrome n=1. Ten patients (28%) underwent allo-SCT as part of planned primary therapy after achieving their first remission [6 were in complete remission 1 (CR1) and 4 were in partial remission 1 (PR1)], whereas 26 patients (72%) underwent allo-SCT for relapsed/refractory disease. CHOP was administered in 19 patients (53%) as the primary therapy. 17 (47%) patients received alternative chemotherapy regimen due to patient and/or physician preference. The clinical status at the time of transplantation was CR in 12 patients (33%), relapsed sensitive disease n=10 (28%), relapsed untreated n=5 (14%), partial remission (PR) in 5 (14%), primary progressive disease n=3 (8%) and relapsed resistant disease n=1 (3%). Thirty two patients (89%) underwent myeloablative conditioning, 4 (11%) underwent reduced intensity conditioning (RIC). The conditioning regimens included: cyclophosphamide/TBI n=24 (67%), busulfan/cyclophosphamide n=5 (14%), fludarabine containing reduced intensity n=4 (11%), and other regimens n= 3 (8%). With a median follow-up of alive patients from the time of allo-SCT of 69 months (range 1-186 months). At last follow-up, 17 (47%) patients have died, 6 from disease relapse, 5 from graft vs host disease (GVHD), 2 from regimen related toxicity and 4 from other causes. Nineteen patients (53%) still alive at last follow up post-transplant of which 14 (39%) still in remission. The 5-year event free survival (EFS) and overall survival (OS) from the time of allo-SCT of all patients were 43% and 63%, respectively. For PTCL-NOS the 5-year EFS and OS were 52% and 69%, respectively. Table 1 summarizes the patients' characteristics. Figures 1 and 2 shows the Kaplan-Meier curves for OS and EFS respectively. Conclusion: Allo-SCT can be effective strategy in select patients with relapsed/refractory PTCL and those with high risk histologies in the upfront setting PTCL with an acceptable toxicity. Disclosures Toze: Roche Canada: Research Funding. Sehn:roche/genentech: Consultancy, Honoraria; amgen: Consultancy, Honoraria; seattle genetics: Consultancy, Honoraria; abbvie: Consultancy, Honoraria; TG therapeutics: Consultancy, Honoraria; celgene: Consultancy, Honoraria; lundbeck: Consultancy, Honoraria; janssen: Consultancy, Honoraria. Scott:NanoString Technologies: Patents & Royalties: named inventor on a patent for molecular subtyping of DLBCL that has been licensed to NanoString Technologies. Villa:Lundbeck: Honoraria; Roche: Honoraria, Research Funding; Celgene: Honoraria. Connors:NanoString Technologies: Research Funding; F Hoffmann-La Roche: Research Funding; Bristol Myers Squib: Research Funding; Seattle Genetics: Research Funding; Millennium Takeda: Research Funding. Song:Janssen: Honoraria; Otsuka: Honoraria; Celgene: Honoraria, Research Funding.

Favorable Outcome In ALK-Negative Anaplastic Large-Cell Lymphoma Following Intensive Induction Chemotherapy and Autologous Stem Cell Transplantation (ASCT): a Prospective Study by the Nordic Lymphoma Group (NLG-T-01)

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3566-3566 ◽  
Author(s):  
Thomas Relander ◽  
Grete Fossum Lauritzsen ◽  
Esa Jantunen ◽  
Hans Hagberg ◽  
Harald Anderson ◽  
...  
Keyword(s):  
T Cell ◽  
Induction Chemotherapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Serum Lactate Dehydrogenase ◽  
Term Survival

Abstract Abstract 3566 Primary systemic T-cell lymphoma of anaplastic large cell type (ALCL) is an aggressive and predominantly nodal subtype of lymphoma, further subdivided based on expression of the ALK-protein, with ALK-pos ALCL occurring predominantly in younger patients and associated with a favourable prognosis. ALK-neg ALCL is believed to carry a prognosis similar to that of other nodal peripheral T-cell lymphomas and previous studies have shown long-term survival rates below 50%. There is retrospective data suggesting a benefit from ASCT in first-line treatment of this lymphoma subtype. We analyzed the outcome of ALK-neg ALCL patients included in a prospective phase II trial, NLG-T-01, conducted by the Nordic Lymphoma Group. The NLG T-01 trial enrolled 160 patients aged 18–67 years from the Nordic countries with systemic ALK-neg peripheral T-cell lymphoma within the period 2002–2007. The treatment schedule consisted of 6 courses of CHOEP-14 followed by ASCT (BEAM or BEAC) in responding patients. Patients >60 years received CHOP-14 as induction. Altogether, the trial included 31 patients with ALK-neg ALCL (19% of the study population). Median age was 56 years (22-65) with a male:female ratio of 2.4. Stage III-IV was found in 18 patients (58%), B-symptoms in 19 patients (61%) and 6 patients (19%) had a bulky lesion (>10cm). Pre-therapeutic serum lactate dehydrogenase was elevated in 18 patients (58%) and performance score was 2–4 in 10 patients (32%). After 3 and 6 courses of chemotherapy, response status was CR or CRu in 29% and 58% of the patients, respectively. In total, 24 out of 31 patients (77%) underwent BEAM/BEAC therapy followed by ASCT. Four patients did not respond or had disease progression during induction chemotherapy. The remaining 3 patients did not undergo ASCT for other reasons (mobilization failure, lung insufficiency, patient decision, respectively). Overall response rate after ASCT was 74% for the entire initial population and 96% for those undergoing ASCT. Median follow-up was 45 months. Six patients relapsed after ASCT. There was a total of nine deaths (29%): six due to lymphoma, two due to toxicity and one from second malignancy (colon cancer). With a median follow-up of 45 months, 3-year overall and progression-free survival values were 73% and 64%, respectively. Intensive chemotherapy followed by ASCT was feasible in the majority of the patients included in this prospective trial. Long-term outcome appears promising when compared to previously published data, with the survival curve suggesting a plateau. In ASCT eligible patients, intensive induction chemotherapy consolidated by upfront ASCT is an effective treatment that yields outcome results at least as good as those obtained in age-comparable patients with diffuse large B-cell lymphoma. Disclosures: No relevant conflicts of interest to declare.

Nodal Peripheral T-Cell Lymphoma – a Clinical and Epidemiological Analysis at Medicine School of Sao Paulo University

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1706-1706
Author(s):  
Luis Alberto de Padua Covas Lage ◽  
Marianne Castro Goncalves ◽  
Rodrigo Santucci ◽  
Renata Oliveira Costa ◽  
Debora Levy ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
High Risk ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Large Cell ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Free Survival ◽  
Large Cell Lymphoma

Abstract Background: Peripheral T-cell lymphoma (PTCL) are a biologically and clinically heterogeneous group of rare diseases arising from mature or activated post-thymic T lymphocytes. Correspond to 10% to 15% of lymphoid malignancies with marked geographical variation in incidence. According to the WHO classification they are divided into nodal, extranodal, primary cutaneous and leukemic or disseminated and encompass 18 distinct entities. The nodal group involves the peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), angioimmunoblastic lymphoma (AITL), anaplastic large cell lymphoma ALK positive (ALCL-ALK+) and anaplastic large cell lymphoma ALK negative (ALCL-ALK-). The literature of PTCL is scarce, especially in our country where data of epidemiology, clinical features and outcomes are usually rarely available. So, to better understand PTCL we performed a retrospective study with patients treated in a reference service for cancer treatment in Brazil. Methods: Eight-seven nodal PTCL patients treated with anthracyclne-based regimen (CHOP or, CHOEP) from January 2000 to June 2014 were evaluated retrospectively at the Medicine School of Sao Paulo University, Brazil. All patients lower than 60 years were consolidated with autologous hematopoietic stem cell transplantation (ASCT) in first CR or PR except that with ALCL-ALK+ diagnosis. Refractory and relapsed patients were salvaged with 3-4 cycles of IVAC (Ifosphamide 1.5 g/m2 i.v D1-D5, etoposide 100mg/m2 i.v D1-D5, aracytin 2g/m2 i.v twice a day D1-D2) regimen and submitted to ASCT. It was performed a central histopathological review and clinical and epidemiological data were obtained from medical records. Patients were evaluated for overall response (OR) including complete response (CR) and partial response (PR), overall survival (OS) and progression free survival (PFS). Statistical analysis was performed using the STATA-3 program using and a p-value ≤ 0.05 was considered statistically significant. Results: Of the 87 patients, 34 (39.08%) cases were classified as ALCL-ALK-, 27 (31.03%) as PTCL-NOS, 16 (18.39%) as ALCL-ALK+, 6 (6.89%) as AITL and in 4 (4.1%) cases the diagnosis could not be performed and an expansion of the immunohistochemical is ongoing. Thirty-six (45.38%) cases were female and 51(54.62%) were male, 59(67.81%) patients were lower than 60 years. Seventy-six (87.35%) patients presented in advanced stage (III or IV) at diagnosis but 73(83.90%) patients presented an ECOG < 2 and 14(16.10%) ≥ 2. Eighteen (20.70%) patients were of low-risk, 26 (29.88%) of low-intermediate risk and 43(49.42%) of high-intermediate and high-risk of international prognostic index (IPI). The CR and PR was obtained for 44(50.57%) and 8(9.19%), respectively with 59.76% OR. Thirty (34.48%) patients were primary refractory and five remain under treatment. In a median of follow of 30 months, ALCL-ALK+ show higher OS (median 140.98 months) than ALCL-ALK- (44.20 months), PTCL-NOS (median 20.62 months) and AITL (median 7.24 months) (p=0.41) (Figure 1A). The median of PFS was 3.84 months for AITL, 23.44 months for ALCL-ALK+, 40.03 months for PTCL-NOS and was not yet reached for ALCL-ALK- (p=0.0006) (Figure 1B). Figure 1: Overall survival (1A) and Progression Free Survival (1B) of nodal PTCL Figure 1:. Overall survival (1A) and Progression Free Survival (1B) of nodal PTCL Figure 2 Figure 2. Conclusion: In this study we showed that ALCL-ALK+ as well as found in the literature presented a better OS in comparison to others nodal T-cell lymphoma as AITL, PTCL-NOS and ALCL-ALK-. Surprisingly the PFS of ALCL-ALK+ was statistically significant lower than of ALCL-ALK-. We thought that this result may be explained because in our service until to perform this analysis we did not indicate ASCT in first CR for ALCL-ALK+, but for all ALCL-ALK-. This hypothesis may be reinforced as the most of our cases presented high-intermediate and high-risk of IPI and that could equalize the favorable effect of ALK expression. In addition, we changed our approach and we are also indicating ASCT in first line for patients with ALCL-ALK+ with intermediate-high and high-risk of IPI . Disclosures No relevant conflicts of interest to declare.

Event-Free Survival at 12 Months and Subsequent Overall Survival in Patients with Peripheral T-Cell Lymphoma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1501-1501
Author(s):  
Matthew J Maurer ◽  
Fredrik Ellin ◽  
James Cerhan ◽  
Stephen Ansell ◽  
Brian K Link ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
T Cell Lymphomas

Abstract Background: Peripheral T-Cell lymphomas (PTCLs) constitute approximately 10% of lymphoid malignancies and consist of several distinct entities based on pathologic and clinical characteristics. With the exception of a few subtypes (e.g., ALK-positive anaplastic large cell lymphoma (ALCL) and some primary cutaneous or leukemic forms of PTCL), a majority of PTCLs are aggressive as characterized by poor treatment response, rapid disease progression and poor overall survival. We have shown that landmark timepoints of event-free survival after diagnosis can stratify subsequent overall survival (OS) in diffuse large B-cell and follicular lymphoma. Here we evaluate this approach in newly diagnosed aggressive PTCLs treated with anthracyline-based or related chemotherapy. Methods. Newly diagnosed PTCL patients were prospectively enrolled in the University of Iowa/Mayo Clinic Lymphoma SPORE Molecular Epidemiology Resource (MER) from 2002-2012. Clinical data were abstracted from medical records using a standard protocol. For this analysis, we included patients receiving anthracycline-based or other multiagent chemotherapy for the following PTCL subtypes: ALK-negative ALCL (N=24); angioimmunoblastic T-cell lymphoma (AITL, N=34); PTCL, not otherwise specified (NOS; N=60); enteropathy-associated T-cell lymphoma (EATL, N=8); extranodal NK/T-cell lymphoma, nasal type (ENKTL, N=11); and hepatosplenic T-cell lymphoma (HSTCL, N=1). Patients were prospectively followed, and event-free survival (EFS) was defined as time from diagnosis to progression, re-treatment, or death due to any cause. Landmark EFS timepoints were assessed at 12 (EFS12) and 24 (EFS24) months after the date of diagnosis. Subsequent OS was defined as time from a specific endpoint (diagnosis, event or EFS landmark). Replication was performed in a population-based cohort of T-cell lymphomas diagnosed from 2000-2009 from the Swedish Lymphoma Registry. Results. 138 eligible patients were enrolled in the MER from 2002-2012, the median age at diagnosis was 58 years (range, 19-88), 66% were male, 73% had Stage III-IV disease, and 33% had IPI 0-1. At a median follow-up of 47 months (range 11-120), 87 patients (63%) had an event and 70 patients (51%) had died. From diagnosis, only 60 patients were event-free at 12 months (EFS12 45%). Patients who failed to achieve EFS12 had a poor subsequent OS from event (median OS = 6.8 months, 95% CI: 5.3-14.0, figure 1). In contrast, patients who achieved EFS12 had a favorable subsequent OS (median unreached, figure 2). Of the 427 eligible patients in the Swedish registry, the median age at diagnosis was 66 years (range, 18-88), 63% were male, 68% had Stage III-IV disease, and 25% had IPI 0-1. PTCL subtypes were: ALK-negative ALCL (N=89); AITL (N=80); PTCL, NOS (N=183); EATL (N=44); ENKTL (N=24); and HSTCL (N=7). At a median follow-up of 86 months (range 40-158), 333 patients (79%) had an event and 316 patients (74%) had died. From diagnosis, 183 patients were event-free at 12 months (EFS12 44%). Similar to the MER cohort, Swedish patients failing EFS12 had poor subsequent survival (median OS = 3.7 months, 95% CI: 2.9-5.3, figure 1). Swedish patients achieving EFS12 had a favorable subsequent OS (median OS = 89 months, figure 2). Similar results were obtained when conducting landmark analysis at 24 months after diagnosis (EFS24). Conclusion. Relapse and re-treatment events within the first 12 months of diagnosis are associated with very poor OS in PTCL treated with anthracyclines or related chemotherapy, while patients achieving EFS12 have encouraging subsequent OS. Stratifying patients into prognostically distinct subsets using EFS12 may help focus biologic and biomarker studies. EFS12 has potential as an early endpoint for studies of newly diagnosed PTCL. Further investigation of determinants related to post-EFS12 survival is needed. Disclosures Maurer: Kite Pharma: Research Funding. Cerhan:Kite Pharma: Research Funding. Ansell:Bristol-Myers Squibb: Research Funding; Celldex: Research Funding. Link:Genentech: Consultancy, Research Funding; Kite Pharma: Research Funding. Thompson:Kite Pharma: Research Funding. Relander:Respiratorius: Patents & Royalties: valproate for DLBCL.

Survival of Peripheral T-Cell Lymphomas (PTCLs) Patients Following Relapse: Spectrum of Disease and Rare Long-Term Survivors

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 96-96 ◽  
Author(s):  
Vivien Mak ◽  
Joseph M. Connors ◽  
Richard Klasa ◽  
Laurie H. Sehn ◽  
Diego Villa ◽  
...  
Keyword(s):  
T Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Progression Free Survival ◽  
Late Relapse ◽  
Primary Therapy ◽  
Curative Therapy ◽  
Response To Chemotherapy ◽  
The Impact

Abstract Abstract 96 Introduction: Recently, a number of novel therapies have been under investigation in PTCLs, however, it remains a challenge to compare these agents and determine the impact on outcome. The purpose of this population-based study was to determine the spectrum of survival in PTCL patients (pts) following relapse and to explore factors influencing survival. The three most common subtypes encountered in North America were evaluated: PTCL-not otherwise specified (PTCL-NOS), angioimmunoblastic T-cell lymphoma (AILT), anaplastic large cell lymphoma, ALK positive (ALK-pos) and ALK-negative (ALK-neg). Material and Methods: The Centre for Lymphoid Cancer Database was screened to identify all pts ≥ 16 y with the above histologies that relapsed or had progressive disease (PD) following primary therapy. In addition to the timing of relapse (very early < 9 mos from diagnosis; early 9–24 mos and late > 24 mos), clinical information at the time of relapse was collected where possible. Responses were determined by the treating physician: Response = any clinical and/or radiographic response; PD = no change or disease progression. Results: In total, 276 pts diagnosed between 1976 and 2010 were identified with primary progressive or relapsed PTCL with initial diagnoses by the WHO classification. 68 were excluded: unconfirmed pathology (6), CNS disease (5), complications during primary CHT (17), no primary chemotherapy (CHT) (27), incomplete chart or lost follow-up (13). 208 pts were analyzed (PTCL-NOS = 109 (52%), ALCL = 54 (26%) (ALK-pos = 18; ALK-neg = 33; ALK status unknown = 3), AILT = 45 (22%). The majority of pts received anthracyclines as part of their primary CHT (89%). The median age at the time of relapse was 62.5 y (range 20 to 86 y) (PTCL-NOS 62 y, ALK-neg 62 y, ALK-pos 40.5 y, AILT 68 y). 129 (62%) pts were refractory to initial CHT. 53 pts were planned for HDC/SCT, however, only 38 (72%) ultimately received it (allo 17, auto 21). 37 pts (18%) were either too ill for any therapy (34) or refused therapy (3). The remaining pts received some type of treatment for their relapsed PTCL: systemic CHT (gemcitabine, CHOP(like), alkylators alone) (103) radiation alone (19) or steroids (11). The median follow-up for surviving pts after relapse/progression was ∼ 4 y. The median overall survival (OS) following relapse for the whole cohort was 7.0 mos (HDC/SCT 47.1 mos; no HDC/SCT 5.4 mos). The median progression free survival (PFS) following relapse was 4.6 mos (HDC/SCT 27.7 mos, no HDC/SCT 2.8 mos). The 3 y OS and PFS following relapse were 55% and 48%, respectively in the HDC/SCT group and similar whether an autologous or allogeneic SCT was performed. The corresponding 3 y OS and PFS estimates in the no HDC/SCT group were19% and 13.5 %, respectively. There was no difference in OS and PFS amongst the histologic subtypes. Considering the no HDC/SCT pts who received CHT (n=103), 55% were determined to have to have had a response to chemotherapy, and the median OS and PFS was 7.0 mos and 4.0 mos, respectively (responders vs non-responders/PD OS 16.7 mos vs 3.0 mos, p<.0001; responders vs non-responders/PD PFS 8.2 mos vs 1.4 mos, p<.0001). In multivariate analysis, the secondary IPI (sIPI), PS ≥ 2, late relapse and HDC/SCT were all prognostic for both PFS (sIPI ≥3 (HR 1.8, p=.009), PS ≥2 (HR 2, p =.002), HDC/SCT(HR.28, p<.0001), late relapse > 24 mos (HR=.64, p<.0001)) and OS (sIPI (HR 1.84, p=.010), PS (HR 2.5, p<.0001) HDC/SCT (HR.46, p=.003) late relapse (HR.65, p<.0001)). Of interest, 28 pts relapsed > 24 mos from the date of diagnosis (PTCL-NOS 12 (43%); ALK-neg ALCL 6 (21%); ALK-pos ALCL 3 (11%); AILT 6 (21%)) and only 8 (31%) subsequently received HDC/SCT but the median PFS and OS was very favourable in this group, 25.4 mos and 41.4 mos, respectively (no HDC/SCT PFS 14 mos and OS 32.3 mos). Conclusions: The outcome of the majority of pts with relapsed/progressive PTCL is poor and with brief remissions to systemic therapy, highlighting the urgent need for novel agents specifically active in PTCL. Outcomes were far superior in pts who were able to be transplanted and efforts need to focus on expanding the number of pts eligible for this curative therapy. Standard clinical factors were prognostic at relapse and are critical when comparing the efficacy of new agents. PTCL pts with rare, very late relapses have a much more favourable prognosis and further highlight the diverse disease biology of PTCLs. Disclosures: Sehn: Roche/Genentech: Consultancy, Honoraria, Research Funding. Villa:Roche: Research Funding. Shenkier:Roche: Research Funding. Savage:Celgene: Consultancy; Allos Therapeutics: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria.

Brentuximab vedotin in real life, a seven year experience in patients with refractory/relapsed CD30+ T cell lymphoma

2020 ◽  
pp. 107815522096861
Author(s):  
Lucie Oberic ◽  
Faustine Delzor ◽  
Caroline Protin ◽  
Sophie Perriat ◽  
Camille Laurent ◽  
...  
Keyword(s):  
T Cell ◽  
Combination Treatment ◽  
Cell Lymphoma ◽  
Real Life ◽  
Progression Free Survival ◽  
Large Cell ◽  
Complete Response ◽  
Brentuximab Vedotin ◽  
T Cell Lymphoma ◽  
T Cell Lymphomas

Introduction Brentuximab vedotin (Bv) has been approved for the treatment of Refractory/Relapsed (R/R) Anaplastic Large Cell Lymphomas (ALCL) and cutaneous T-Cell Lymphomas, but is also effective in other CD30+ malignancies. We report here the outcomes of patients with various R/R Peripheral T Cell Lymphoma (PTCL) treated with Bv in real life practice. Method This was a retrospective, single-center study based on medical records of patients with R/R PTCL treated either with Bv alone or in combination with chemotherapy. Results Among 27 patients treated with Bv, neutropenia was the main serious adverse event observed in particular when Bv was used as combination treatment. The complete Response Rates (CRR) was 40.7%; it was significantly improved when Bv was used as combination treatment. The majority of eligible patients (7/10) underwent Stem Cell Transplantation. Median Progression Free Survival (PFS) and Overall Survival (OS) were 5.2 months and 12.5 months respectively. Conclusion Our current study shows that Bv used in combination with chemotherapy provides a high CRR and thereby allows SCT in R/R PTCL. The use of Bv treatments in this setting warrants further investigation.

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

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3000-3000 ◽  
Author(s):  
Andrea Janikova ◽  
Robert Pytlik ◽  
Pavel Klener ◽  
Zbynek Bortlicek ◽  
Vit Campr ◽  
...  
Keyword(s):  
T Cell ◽  
Elderly Patients ◽  
Research Funding ◽  
Cell Lymphoma ◽  
Large Cell ◽  
Population Based ◽  
T Cell Lymphoma ◽  
First Line ◽  
Peripheral T Cell Lymphoma ◽  
Age Related

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

Treatments and Outcomes of Patients With Extranodal Natural Killer/T-Cell Lymphoma Diagnosed Between 2000 and 2013: A Cooperative Study in Japan

2017 ◽  
Vol 35 (1) ◽  
pp. 32-39 ◽  
Author(s):  
Motoko Yamaguchi ◽  
Ritsuro Suzuki ◽  
Masahiko Oguchi ◽  
Naoko Asano ◽  
Jun Amaki ◽  
...  
Keyword(s):  
T Cell ◽  
Natural Killer ◽  
Cell Lymphoma ◽  
Interleukin 2 ◽  
Progression Free Survival ◽  
Free Survival ◽  
Natural Killer T Cell ◽  
Soluble Interleukin 2 Receptor ◽  
Killer T Cell

Purpose To elucidate the management and outcomes of patients with extranodal natural killer/T-cell lymphoma, nasal type (ENKL), who were diagnosed between 2000 and 2013 in Japan. Patients and Methods Data from 358 patients with ENKL diagnosed between 2000 and 2013 from 31 institutes were retrospectively analyzed. Results Patients’ median age was 58 years, and 257 (72%) had localized disease. The most common first-line treatment was radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) (66%) for localized ENKL and L-asparaginase–containing chemotherapy (30%) for advanced ENKL. With a median follow-up of 5.8 years, overall survival (OS) rates at 5 years for localized and advanced ENKL were 68% and 24%, respectively. The prognostic index of natural killer lymphoma was validated in our study, although only 4% of patients with localized ENKL were classified as high risk. With a median follow-up of 5.6 years, OS and progression-free survival at 5 years in the 150 patients who received RT-DeVIC in clinical practice were 72% (95% CI, 63% to 78%) and 61% (95% CI, 52% to 69%), respectively. Toxicities of RT-DeVIC were comparable to those in a previous trial. Multivariate analysis in patients with localized ENKL who received RT-DeVIC identified elevated soluble interleukin-2 receptor as an independent predictive factor for worse OS and progression-free survival (adjusted hazard ratios, 2.28 and 2.46; 95% CI, 1.24 to 4.23 and 1.42 to 4.28; P = .008 and .0014, respectively). Conclusion Favorable OS in response to new treatments was demonstrated in a large number of patients. Improved treatment approaches are needed for localized ENKL exhibiting elevated pretreatment soluble interleukin-2 receptor.

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