Pralatrexate in patients with recurrent or refractory peripheral T-cell lymphomas: a multicenter retrospective analysis

AbstractPeripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas with poor clinical outcomes. Pralatrexate showed efficacy and safety in recurrent or refractory PTCLs. The purpose or this study was to investigate the efficacy and safety of pralatrexate in relapsed or refractory PTCLs in real-world practice. This was an observational, multicenter, retrospective analysis. Between December 2012 and December 2016, a total of 38 patients with relapsed or refractory PTCLs were treated with pralatrexate at 10 tertiary hospitals in Korea. Patients received an intravenous infusion of pralatrexate at a dose of 30 mg/m2/week for 6 weeks on a 7-week schedule. Modified dosing and/or scheduling was allowed according to institutional protocols. Median patient age was 58 years (range, 29–80 years) and the most common subtype was peripheral T-cell lymphoma, not otherwise specified (n = 23, 60.5%). The median dosage of pralatrexate per administration was 25.6 mg/m2/wk (range, 15.0–33.0 mg/m2/wk). In intention-to-treat analysis, 3 patients (7.9%) showed a complete response and 5 patients (13.2%) showed a partial response, resulting in an overall response rate (ORR) of 21.1%. The median duration of response was 7.6 months (range, 1.6–24.3 months). The median progression-free survival (PFS) was 1.8 months (95% confidence interval [CI], 1.7–1.8 months) and the median overall survival was 7.7 months (95% CI, 4.4–9.0 months). The most common grade 3/4 adverse events were thrombocytopenia (n = 13, 34.2%), neutropenia (n = 7, 23.7%), and anemia (n = 7, 18.4%). Our study showed relatively lower ORR and shorter PFS in patients with recurrent or refractory PTCLs treated with pralatrexate in real-world practice. The toxicity profile was acceptable and manageable. We also observed significantly lower dose intensity of pralatrexate in real-world practice.

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Granzyme B-expressing peripheral T-cell lymphomas: neoplastic equivalents of activated cytotoxic T cells with preference for mucosa- associated lymphoid tissue localization

Blood ◽

10.1182/blood.v84.11.3785.bloodjournal84113785 ◽

1994 ◽

Vol 84 (11) ◽

pp. 3785-3791 ◽

Cited By ~ 80

Author(s):

PC de Bruin ◽

JA Kummer ◽

P van der Valk ◽

P van Heerde ◽

PM Kluin ◽

...

Keyword(s):

T Cells ◽

T Cell ◽

Tumor Cells ◽

Lymphoid Tissue ◽

Cytotoxic T Cells ◽

Granzyme B ◽

Clinical Behavior ◽

T Cell Lymphomas ◽

Hodgkin's Lymphomas ◽

Peripheral T Cell Lymphomas

T-cell non-Hodgkin's lymphomas can be considered the neoplastic equivalents of immunologically functional, site-restricted T lymphocytes. Little is known about the occurrence and clinical behavior of T-cell lymphomas that are the neoplastic equivalents of different functional T-cell subsets. Here, we investigated the prevalence, preferential site, immunophenotype, and clinical behavior of the neoplastic equivalents of activated cytotoxic T cells (CTLs) in a group of 140 nodal and extranodal T-cell lymphomas. Activated CTLs were shown immunohistochemically with a monoclonal antibody against granzyme B, a major constituent of the cytotoxic granules of activated T cells. Granzyme B-positive T-cell lymphomas were mainly found in mucosa- associated lymphoid tissue (MALT; nose, 63% of the cases; gastrointestinal tract, 46%; and lung, 33%). Granzyme B-positive cases with primary localization in MALT were more often associated with angioinvasion (P = .005), necrosis (P = .002), and histologic characteristics of celiac disease in adjacent mucosa not involved with lymphoma. Eosinophilia was more often observed in granzyme B-negative cases (P = .03). Most cases belonged to the pleomorphic medium- and large-cell group of the Kiel classification. CD30 expression was more often found in granzyme B-positive lymphomas of MALT (P = .04), whereas CD56 expression was exclusively found in nasal granzyme B-positive lymphomas. Immunophenotypically, most of the cases should be considered as neoplastic equivalents of activated CTLs based on the presence of T- cell markers on tumor cells. In two cases of nasal lymphoma, tumor cells probably were the neoplastic counterparts of natural killer cells. The prognosis of the granzyme B-positive gastrointestinal T-cell lymphomas was poor but did not differ from granzyme B-negative gastrointestinal T-cell lymphomas. This indicates that, in peripheral T- cell lymphomas, site of origin is more important as a prognostic parameter than derivation of activated CTLs.

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

Journal of Oncology Pharmacy Practice ◽

10.1177/1078155220968615 ◽

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.

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Real-World Efficacy and Safety of Lenvatinib in Korean Patients with Advanced Hepatocellular Carcinoma: A Multicenter Retrospective Analysis

Liver Cancer ◽

10.1159/000508901 ◽

2020 ◽

Vol 9 (5) ◽

pp. 613-624 ◽

Cited By ~ 2

Author(s):

Jaekyung Cheon ◽

Hong Jae Chon ◽

Yeonghak Bang ◽

Neung Hwa Park ◽

Jung Woo Shin ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Retrospective Analysis ◽

Real World ◽

Checkpoint Inhibitors ◽

Clinical Trial Data ◽

Progression Free Survival ◽

Phase Iii ◽

Advanced Hepatocellular Carcinoma ◽

Efficacy And Safety ◽

First Line

Introduction/Objective: Lenvatinib demonstrated efficacy and safety in patients with advanced hepatocellular carcinoma (HCC) in the randomized phase III REFLECT trial. Considering the discrepancies in patients between clinical trial data and daily practice, an account of practical experience is needed. Methods: We conducted a multicenter retrospective analysis in which 3 tertiary referral centers participated. A total of 92 patients with advanced HCC treated with lenvatinib between September 2018 and January 2020 were analyzed. Results: Lenvatinib was used as the first-line therapy for 67 (72.8%) patients, and for 25 (27.2%) patients previously treated with other systemic therapy including immune checkpoint inhibitors. At the time of initiation of lenvatinib, 74 (80.4%) and 18 (19.6%) patients were classified as Child-Pugh A and B, respectively. Thirty-five patients (38.0%) had extensive disease that would have excluded them from the REFLECT trial. In the Child-Pugh A group, the response rate graded according to the Response Evaluation Criteria in Solid Tumors v1.1 was 21.1%, median progression-free survival (PFS) was 4.6 (95% confidence interval [CI] 3.1–6.1) months, and overall survival (OS) was 10.7 (95% CI 4.8–16.5) months for patients treated with first-line lenvatinib (n = 57). With second- or later-line lenvatinib (n = 17), median PFS and OS were 4.1 (95% CI 3.1–5.1) and 6.4 (95% CI 5.1–7.7) months, respectively. In the Child-Pugh B group (n = 18), median PFS and OS were 2.6 (95% CI 0.6–4.6) and 5.3 (95% CI 2.0–8.5) months, respectively. The most common grade 3–4 toxicities were hyperbilirubinemia (n = 8; 8.7%), AST elevation (n = 6; 6.5%), and diarrhea (n = 5; 5.4%) across all study patients. Conclusions: In this real-world study, lenvatinib was found to be well tolerated and effective in more heterogeneous HCC patient populations.

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An overview of cutaneous T cell lymphomas

F1000Research ◽

10.12688/f1000research.8829.1 ◽

2016 ◽

Vol 5 ◽

pp. 1882 ◽

Cited By ~ 26

Author(s):

Nooshin Bagherani ◽

Bruce R. Smoller

Keyword(s):

T Cell ◽

T Lymphocytes ◽

Mycosis Fungoides ◽

Annual Incidence ◽

Heterogeneous Group ◽

Not Otherwise Specified ◽

T Cell Lymphomas ◽

Hodgkin's Lymphomas ◽

Diagnosis Therapy ◽

Peripheral T Cell Lymphomas

Cutaneous T cell lymphomas (CTCLs) are a heterogeneous group of extranodal non-Hodgkin’s lymphomas that are characterized by a cutaneous infiltration of malignant monoclonal T lymphocytes. They typically afflict adults with a median age of 55 to 60 years, and the annual incidence is about 0.5 per 100,000. Mycosis fungoides, Sézary syndrome, and primary cutaneous peripheral T cell lymphomas not otherwise specified are the most important subtypes of CTCL. CTCL is a complicated concept in terms of etiopathogenesis, diagnosis, therapy, and prognosis. Herein, we summarize advances which have been achieved in these fields.

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Autologous stem cell transplantation in first complete remission may not extend progression-free survival in patients with peripheral T cell lymphomas

American Journal of Hematology ◽

10.1002/ajh.24372 ◽

2016 ◽

Vol 91 (7) ◽

pp. 672-676 ◽

Cited By ~ 13

Author(s):

Clinton Yam ◽

Daniel J. Landsburg ◽

Kevin T. Nead ◽

Xinyi Lin ◽

Anthony R. Mato ◽

...

Keyword(s):

Stem Cell ◽

T Cell ◽

Complete Remission ◽

Stem Cell Transplantation ◽

Autologous Stem Cell Transplantation ◽

Progression Free Survival ◽

Free Survival ◽

T Cell Lymphomas ◽

First Complete Remission ◽

Peripheral T Cell Lymphomas

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Recurrent TET2 mutations in peripheral T-cell lymphomas correlate with TFH-like features and adverse clinical parameters

Blood ◽

10.1182/blood-2012-02-408542 ◽

2012 ◽

Vol 120 (7) ◽

pp. 1466-1469 ◽

Cited By ~ 253

Author(s):

François Lemonnier ◽

Lucile Couronné ◽

Marie Parrens ◽

Jean-Philippe Jaïs ◽

Marion Travert ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Prognostic Index ◽

Progression Free Survival ◽

T Cell Lymphoma ◽

Not Otherwise Specified ◽

T Cell Lymphomas ◽

Stage Disease ◽

Peripheral T Cell Lymphomas

Abstract Inactivating mutations of the Ten-Eleven Translocation 2 (TET2) gene were first identified in myeloid malignancies and more recently in peripheral T-cell lymphomas (PTCLs). In the present study, we investigated the presence of TET2 coding sequence mutations and their clinical relevance in a large cohort of 190 PTCL patients. TET2 mutations were identified in 40 of 86 (47%) cases of angioimmunoblastic T-cell lymphoma (AITL) and in 22 of 58 (38%) cases of peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), but were absent in all other PTCL entities, with the exception of 2 of 10 cases of enteropathy-associated T-cell lymphoma. Among PTCL-NOS, a heterogeneous group of lymphoma-comprising cases likely to derive from Th follicular (TFH) cells similarly to AITL, TET2 mutations were more frequent when PTCL-NOS expressed TFH markers and/or had features reminiscent of AITL (58% vs 24%, P = .01). In the AITL and PTCL-NOS subgroups, TET2 mutations were associated with advanced-stage disease, thrombocytopenia, high International Prognostic Index scores, and a shorter progression-free survival.

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Multicenter, phase II study of bendamustine in refractory or relapsed T-cell lymphoma: The BENTLY trial.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.8026 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 8026-8026 ◽

Cited By ~ 1

Author(s):

Remy Gressin ◽

Gandhi Laurent Damaj ◽

Kamal Bouabdallah ◽

Guillaume Cartron ◽

B Choufi ◽

...

Keyword(s):

T Cell ◽

Cell Lymphoma ◽

International Prognostic Index ◽

Single Agent ◽

Prognostic Index ◽

Progression Free Survival ◽

Complete Response ◽

T Cell Lymphoma ◽

Previous Response ◽

T Cell Lymphomas

8026 Background: T-cell lymphomas have a poor prognosis with few options of effective treatment. This study determined the efficacy and safety of bendamustine as a single agent in the treatment of refractory or relapsed T-cell lymphomas. Methods: Patients with histologically confirmed peripheral T-cell lymphoma (PTCL) or cutaneous T-cell lymphoma (CTCL), who had previously received at least one line of chemotherapy were selected. Bendamustine was administered IV at the dosage of 120 mg/m2 on days 1 and 2 every 3 weeks, for 6 cycles. Treatment response was assessed using the IWC for non-Hodgkin's lymphoma. The primary end point was overall response rate (ORR). Secondary end points were duration of response (DoR), progression-free survival (PFS), and overall survival (OS), NCT00959686. Results: Twenty two female and 38 male were included. The median age was 66 years with more 1/4 of them > 75. Histology was predominantly angio-immunoblastic lymphadenopathy (n=32) and PTCL-nos (n=23). The median previous line of chemotherapy was 1 (1-3). Nearly one half (45%) of the patients was refractory to the last previous chemotherapy and the median duration of the best previous response was 6.6 (1.5-67) months. The disease was disseminated in the majority of case (87%) and the international prognostic index (IPI) was high (3–5) in 68% of the patients. Twenty patients (33%) received less than 3 cycles of bendamustine. The major reason for early discontinuation was disease progression. In the Intent-To-Treat (ITT) population, the best ORR was 50%, including complete response (CR) in 28% and partial response (PR) in 22 %. Bendamustine showed a consistency in the efficacy as a function of major disease characteristics. The median values for DoR, PFS and OS were 3.5, 4 and 6 months respectively. The most frequent grade 3/4 AEs were neutropenia (30%), thrombocytopenia (24%) and infections (20%). Conclusions: Bendamustine is active in high risk refractory and relapsed T-cell lymphoma with manageable toxicity.

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Retrospective analysis of peripheral T cell lymphomas

Annals of Oncology ◽

10.1093/annonc/mdx697.028 ◽

2017 ◽

Vol 28 ◽

pp. ix81

Author(s):

Satoshi Kaito ◽

Yusuke Kanemasa ◽

Yuki Sasaki ◽

Toshihiro Okuya ◽

Tsukasa Yamaguchi ◽

...

Keyword(s):

T Cell ◽

Retrospective Analysis ◽

T Cell Lymphomas ◽

Peripheral T Cell Lymphomas

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Efficacy and safety of apatinib in treatment of gastric cancer: A real-world study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.3_suppl.182 ◽

2021 ◽

Vol 39 (3_suppl) ◽

pp. 182-182

Author(s):

Yijie Ma ◽

Hong Zong ◽

Junsheng Wang ◽

Yanzhen Guo ◽

Huaimin LIU ◽

...

Keyword(s):

Gastric Cancer ◽

Adverse Events ◽

Real World ◽

Progression Free Survival ◽

Complete Response ◽

Efficacy And Safety ◽

Efficacy Evaluation ◽

Third Line ◽

Grade 3 ◽

Gastric Cancer Patients

182 Background: Apatinib is a small molecule TKI inhibitor, which had been approved in China for treatment of advanced gastric cancer refractory to two or more lines of prior chemotherapy. Its efficacy and safety have been demonstrated in previous randomized controlled clinical studies. However, the efficacy and safety of apatinib in real world is lacking. This study aimed to evaluate the anti-tumor activity and toxicity of apatinib in real world. Methods: Patients older than 18 years with histologically diagnosed with gastric cancer were enrolled and treated with either apatinib alone or in combination with other drugs. The primary endpoint was progression-free survival (PFS), and secondary endpoints were overall survival (OS), overall response rate (ORR) and disease control rate (DCR). The adverse events were also recorded. Results: From March 2018 to March 2019, a total of 1000 patients were enrolled. Among them, 48(0.48%), 13(0.13%), 225 (22.5%), 389 (38.9%), and 325 (32.5%) patients received apatinib as postoperative auxiliary-, neoadjuvant-, first-, second-, and third- or higher line therapy, respectively. Efficacy evaluation was performed in 901 patients. Thirty-five patients achieved complete response (CR), 116 patients achieved partial response (PR), 596 patients achieved stable disease (SD), and 154 patients had progressive disease (PD), illustrating an ORR of 16.76% and a DCR of 82.91%. The mPFS was 5.32 months (95% CI, 4.93-5.75), and mOS was 9.76 months (95% CI, 8.97-10.81). In addition, the mOS of apatinib in first-line, second-line, and third-line treatments were 12.68 months, 9.49 months, and 7.62 months, respectively. Patients received apatinib in combination with other drugs had longer survival than apatinib alone, with mPFS 5.62 months vs 4.47 months and mOS 10.81 months vs 7.95 months. Such phenomenon was also observed in ORR (18.21% vs 13.04%, P< 0.001) and DCR (84.88% vs 77.87%, P< 0.001). The main adverse events (AE) were anemia (67.2%), thrombocytopenia (36.2%), leukopenia (34.5%)and anorexia (37.6%). The most common grade 3-4 adverse events included neutropenia, anemia and thrombocytopenia. Conclusions: In the real world, apatinib showed promising efficacy and manageable toxicities in patients with gastric cancer. Patients benefit more when received apatinib combination therapy. Clinical trial information: NCT03478943.

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