LONG-TERM OUTCOME OF PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA TREATED WITH FIRST-LINE INTENSIVE CHEMOTHERAPY FOLLOWED BY AUTOLOGOUS STEM CELL TRANSPLANTATION

Abstract Background: Peripheral T-cell lymphoma (PTCL) is a group of aggressive non-Hodgkin's lymphomas (NHL) with high heterogeneity. The first-line treatment commonly used for firstly-diagnosed PTCL is the CHOP-like regimen. However, in addition to ALK+ALCL, these regimens present poor long-term survival rate in other subtypes, mostly less than 30-40%. Even with the consolidation of autologous hematopoietic stem cell transplantation, studies have reported that the 5-year overall survival rate is barely about 50%. Therefore, for PTCL patients who have achieved remission and undergone autologous hematopoietic stem cell transplantation, there is an urgent need to explore a maintenance treatment strategy. Chidamide is an oral type of selective HDAC inhibitor with subtype specificity for HDAC 1, 2, 3, and 10. It has a regulatory effect on abnormal epigenetic functions of tumors and a novel induction and activation of cellular immune function. In China, it has been approved for relapsed or refractory PTCL at a dose of 30 mg/time, twice a week. The study of chidamide has proved its satisfactory efficacy and safety characteristics for PTCL again. This study preliminarily evaluates the near term effects of chidamide combined with chemotherapy in the first-line treatment and maintenance value of PTCL through retrospective analysis. Methods: We collect adult peripheral T-cell lymphomas inducing by CHOP-like regimen with chidamide or not. The complete response rate (CR), objective response rate (ORR), progression-free survival time (PFS) and overall survival time (OS) of patients in the combined chidamide group and non-combined group were separately analyzed and evaluated. Meanwhile, the OS in the chidamide-maintenance and non-chidamide maintenance of the PTCLs were also brought to study. Results: A total of 82 patients recruited, with a median age of 60 years (14-79 years), including 45 peripheral T-cell lymphoma (PTCL-NOS), 23 angioimmunoblastic lymphoma (AITL), 14 anaplastic large cell lymphoma (ALCL), and the follow-up time cutoff was April 30, 2021. Among 82 patients, 39 patients were treated with chidamide+CHOP-like as the first-line treatment, and 43 patients were treated with CHOP-like as the first-line treatment. The CR rate of the first-line combined chidamide group was 62%, and the ORR was 87%. The CR rate of the first-line non-combined chidamide group was 42% and the ORR was 74%. There was no significant difference in CR rate and ORR between the two groups, but the CR rate has potential clinical benefits. The median PFS of the combined chidamide group was longer than that of the non-combined group by 8 months (18.9m VS 10.9m), but there was no significant statistical difference (p=0.255). Among 82 patients, regardless of first-line treatment or salvage treatment, 42 patients in the maintenance treatment group of chidamide did not reach the median OS, and the median OS of 40 patients in the non-maintenance group was 18.9 months. The difference between the groups was statistically significant (p <0.001). There were totally 66 patients responding to the first-line treatment (CR+PR). 8 patients with sequential autologous stem cell transplantation (ASCT), 34 patients with chidamide maintenance treatment, and both groups didn't reach the median OS. The third group including 24 patients who did not undergo ASCT or chidamine maintenance presenting a median OS of 45.5 months. However, due to the limitation of follow-up time, the difference between the groups was not statistically significant, but the first two groups showed a trend of clinical benefit, which requires further follow-up. During the follow-up period, 48 patients had disease progression with first-line treatment, 23 patients had disease progression using combined chidamide as salvage treatment, and 25 patients in the non-combined chidamide group suffered disease progression. There was a statistically significant difference in OS between the groups (mOS: less than 11.8 months of VS, p =0.03). Subgroup analysis showed that chidamide maintenance treatment in the PTCL-NOS group provided a significant improvement in the prognosis (mOS: 21m VS 5.6m). Conclusion: It preliminarily suggested that chidamide maintenance therapy for PTCL provided an ideal survival benefit, especially In patients with PTCL-NOS subtypes. First-line treatment combined with chidamide and chidamide maintenance therapy may improve the poor survival prognosis. Disclosures No relevant conflicts of interest to declare.

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Intensive Induction Chemotherapy Followed by Autologous Stem Cell Transplantation (ASCT) In Patients with Enteropathy-Associated T-Cell Lymphoma: a Prospective Study by the Nordic Lymphoma Group (NLG-T-01)

Blood ◽

10.1182/blood.v116.21.3565.3565 ◽

2010 ◽

Vol 116 (21) ◽

pp. 3565-3565 ◽

Cited By ~ 4

Author(s):

Esa Jantunen ◽

Thomas Relander ◽

Grete Fossum Lauritzsen ◽

Hans Hagberg ◽

Harald Anderson ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Prospective Study ◽

Induction Chemotherapy ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

Serum Lactate Dehydrogenase ◽

Term Outcome ◽

Long Term Outcome

Abstract Abstract 3565 Enteropathy-associated T-cell lymphoma (ETCL) is a rare lymphoma often, but not always, associated with celiac disease and characterized by poor prognosis when treated with conventional chemotherapy. In previous studies long-term survival has been achieved in only 10–20% of the patients. Limited data is available on the feasibility and efficacy of intensive induction chemotherapy followed by autologous stem transplantation (ASCT) in this rare lymphoma entity. We therefore specifically analysed the outcome of ETCL patients included in a large prospective phase II study (NLG-T-01) performed by the Nordic Lymphoma Group. The NLG-T-01 study included 160 patients with systemic alk-negative peripheral T-cell lymphoma over the period 2002–2007. The patients received CHOEP-14 × 6 followed by ASCT after BEAM or BEAC in responsive patients. The study included altogether 21 patients (13 %) with ETCL. There were 16 males and 5 females with a median age of 55 years (32-65) at diagnosis. Eighteen patients (86 %) had advanced disease, three patients (14 %) had a bulky tumour, nine patients (43 %) presented with B symptoms and four (19%) with elevated serum lactate dehydrogenase. Response status after three and six courses was CR or CRu in 67 % patients. Fourteen patients (67 %) received BEAM or BEAC supported by blood stem cell graft (median number of stem cells infused 5.4 × 106/kg). Of these, 6 patients relapsed with a median of 219 days from ASCT. Of the 7 patients (33%), who did not reach ASCT because of refractory/progressive disease, 5 died early due to lymphoma. At a median follow-up of 45 months, 10 patients (45 %) are alive. The progression-free survival is 40 %. One patient (5%) died due to early transplant-related cause (disseminated candidiasis). In this prospective study, intensive induction chemotherapy followed by ASCT was feasible in the majority of younger patients with EATL. In a subset of patients, who should clinically and biologically be further characterized, long-term outcome seems promising when compared to historical controls. Whether addition of other chemotherapeutic agents, antibodies such as alemtuzumab or other biologicals may further improve long-term outcome remains to be studied. Disclosures: No relevant conflicts of interest to declare.

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Intensive chemotherapy (high-dose CHOP/ESHAP regimen) followed by autologous stem-cell transplantation in previously untreated patients with peripheral T-cell lymphoma

Annals of Oncology ◽

10.1093/annonc/mdn022 ◽

2008 ◽

Vol 19 (5) ◽

pp. 958-963 ◽

Cited By ~ 145

Author(s):

S. Mercadal ◽

J. Briones ◽

B. Xicoy ◽

C. Pedro ◽

L. Escoda ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

High Dose ◽

Intensive Chemotherapy ◽

Peripheral T Cell Lymphoma

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Primary Treatment Response Rather than Front Line Stem Cell Transplantation Is Crucial for Long Term Outcome of Peripheral T-Cell Lymphomas

PLoS ONE ◽

10.1371/journal.pone.0121822 ◽

2015 ◽

Vol 10 (3) ◽

pp. e0121822 ◽

Cited By ~ 5

Author(s):

Giuseppe Gritti ◽

Cristina Boschini ◽

Andrea Rossi ◽

Federica Delaini ◽

Anna Grassi ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

Primary Treatment ◽

Front Line ◽

Term Outcome ◽

Long Term Outcome ◽

T Cell Lymphomas ◽

Peripheral T Cell Lymphomas

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Autologous stem cell transplantation as consolidation therapy for patients with peripheral T cell lymphoma in first remission: long-term outcome and risk factors analysis

Annals of Hematology ◽

10.1007/s00277-013-1716-2 ◽

2013 ◽

Vol 92 (7) ◽

pp. 925-933 ◽

Cited By ~ 6

Author(s):

Anna Czyz ◽

Joanna Romejko-Jarosinska ◽

Grzegorz Helbig ◽

Wanda Knopinska-Posluszny ◽

Lidia Poplawska ◽

...

Keyword(s):

Risk Factors ◽

Stem Cell ◽

Cell Lymphoma ◽

Consolidation Therapy ◽

Peripheral T Cell Lymphoma ◽

Term Outcome ◽

Long Term Outcome ◽

Factors Analysis ◽

First Remission

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

Blood ◽

10.1182/blood.v128.22.1830.1830 ◽

2016 ◽

Vol 128 (22) ◽

pp. 1830-1830

Author(s):

Fredrik Ellin ◽

Knut Liestøl ◽

Susanna Mannisto ◽

Grete F Lauritzsen ◽

Esa Jantunen ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Stem Cell Transplantation ◽

Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Cell Lymphoma ◽

T Cell Lymphoma ◽

High Dose ◽

Peripheral T Cell Lymphoma

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

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