scholarly journals Venetoclax Shows Low Therapeutic Activity in BCL2-Positive Relapsed/Refractory Peripheral T-Cell Lymphoma: A Phase 2 Study of the Fondazione Italiana Linfomi

2021 ◽  
Vol 11 ◽  
Author(s):  
Laura Ballotta ◽  
Pier Luigi Zinzani ◽  
Stefano Pileri ◽  
Riccardo Bruna ◽  
Monica Tani ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Tumor Lysis Syndrome ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Clinical Trial Registration ◽  
Prospective Phase ◽  
Bcl2 Protein

Patients with relapsed/refractory (R/R) peripheral T-cell lymphoma (PTCL) have a poor prognosis, with an expected survival of less than 1 year using standard salvage therapies. Recent advances in our understanding of the biology of PTCL have led to identifying B-Cell Lymphoma 2 (BCL2) protein as a potential therapeutic target. BLC2 inhibitor venetoclax was investigated in a prospective phase II trial in patients with BCL2-positive R/R PTCL after at least one previous standard line of treatment (NCT03552692). Venetoclax given alone at a dosage of 800 mg/day resulted in one complete response (CR) and two stable diseases (SDs) among 17 enrolled patients. The majority of patients (88.2%) interrupted the treatment due to disease progression. No relationship with BCL2 expression was documented. At a median follow-up of 8 months, two patients are currently still on treatment (one CR and one SD). No case of tumor lysis syndrome was registered. Therefore, venetoclax monotherapy shows activity in a minority of patients whose biological characteristics have not yet been identified.Clinical Trial Registrationwww.clinicaltrials.gov (NCT03552692, EudraCT number 2017-004630-29).

Composite diffuse large B-cell lymphoma and CD20-positive peripheral T-cell lymphoma

2011 ◽  
Vol 61 (11) ◽  
pp. 662-666 ◽  
Author(s):  
Sho Yamazaki ◽  
Yosei Fujioka ◽  
Fumihiko Nakamura ◽  
Satoshi Ota ◽  
Aya Shinozaki ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Large B Cell Lymphoma ◽  
Large B Cell

Results From a Pivotal, Open-Label, Phase II Study of Romidepsin in Relapsed or Refractory Peripheral T-Cell Lymphoma After Prior Systemic Therapy

2012 ◽  
Vol 30 (6) ◽  
pp. 631-636 ◽  
Author(s):  
Bertrand Coiffier ◽  
Barbara Pro ◽  
H. Miles Prince ◽  
Francine Foss ◽  
Lubomir Sokol ◽  
...  
Keyword(s):  
T Cell ◽  
Phase Ii ◽  
Systemic Therapy ◽  
Response Rate ◽  
Cell Lymphoma ◽  
Single Agent ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Prior Systemic Therapy

Purpose Romidepsin is a structurally unique, potent class 1 selective histone deacetylase inhibitor. The primary objective of this international, pivotal, single-arm, phase II trial was to confirm the efficacy of romidepsin in patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). Patients and Methods Patients who were refractory to at least one prior systemic therapy or for whom at least one prior systemic therapy failed received romidepsin at 14 mg/m2 as a 4-hour intravenous infusion on days 1, 8, and 15 every 28 days. The primary end point was the rate of complete response/unconfirmed complete response (CR/CRu) as assessed by an independent review committee. Results Of the 131 patients enrolled, 130 had histologically confirmed PTCL by central review. The median number of prior systemic therapies was two (range, one to eight). The objective response rate was 25% (33 of 130), including 15% (19 of 130) with CR/CRu. Patient characteristics, prior stem-cell transplantation, number or type of prior therapies, or response to last prior therapy did not have an impact on response rate. The median duration of response was 17 months, with the longest response ongoing at 34+ months. Of the 19 patients who achieved CR/CRu, 17 (89%) had not experienced disease progression at a median follow-up of 13.4 months. The most common grade ≥ 3 adverse events were thrombocytopenia (24%), neutropenia (20%), and infections (all types, 19%). Conclusion Single-agent romidepsin induced complete and durable responses with manageable toxicity in patients with relapsed or refractory PTCL across all major PTCL subtypes, regardless of the number or type of prior therapies. Results led to US Food and Drug Administration approval of romidepsin in this indication.

Peripheral T cell lymphoma.

1987 ◽  
Vol 5 (5) ◽  
pp. 750-755 ◽  
Author(s):  
R Liang ◽  
D Todd ◽  
T K Chan ◽  
K L Wong ◽  
F Ho ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
Statistical Significance ◽  
Disease Free Survival ◽  
Complete Response ◽  
Small Sample ◽  
T Cell Lymphoma ◽  
Chinese Patients ◽  
Peripheral T Cell Lymphoma ◽  
Small Sample Sizes

Thirty-one Chinese patients with peripheral T cell lymphoma (PTCL) were reviewed. Using the modified Japanese Lymphoma Group classification, there were nine (29%) of the pleomorphic type, 16 (52%) immunoblastic lymphadenopathy (IBL)-like, two (7%) T-zone lymphoma, and one (3%) Lennert's lymphoepithelioid type. Three (9%) were not classifiable. All were positive for T11 (E rosette receptor antigen). Fifty-four percent (15 of 28) were positive predominantly for T4 (helper T cell) and 46% (13/28) for T8 (suppressor T cell). The median age of the patients was 57 years. They usually presented with advanced disease, and while extranodal involvement was common, CNS disease was not seen. The IBL-like type was associated with a positive Coombs' test and polyclonal hypergammaglobulinemia. Five of the nine pleomorphic type were checked for antibody to HTLV-I virus and all were negative. PTCL was associated with poor prognosis, which was not influenced by the histologic subtypes and the T4/T8 phenotypes. The complete response rate of 13 consecutive patients who received the BACOP (bleomycin, doxorubicin, cyclophosphamide, vincristine, and prednisone) L17M regimen was significantly better than the 16 historic controls who received other less-intensive regiments, 84% v 19% (P less than .01). The relapse rate was also significantly lower, 9% v 100% (P less than .001). There appeared to be an improvement in the disease-free survival (DFS) (80% v 0% at 18 months), as well as the overall survival (60% v 36% at 18 months), but the differences did not reach statistical significance due to small sample sizes.

Direct comparisons of peripheral T-cell lymphoma with diffuse B-cell lymphoma of comparable histological grades--should peripheral T-cell lymphoma be considered separately?

1989 ◽  
Vol 7 (6) ◽  
pp. 725-731 ◽  
Author(s):  
A L Cheng ◽  
Y C Chen ◽  
C H Wang ◽  
I J Su ◽  
H C Hsieh ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Induction Chemotherapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
High Grade ◽  
Peripheral T Cell Lymphoma ◽  
Laboratory Features ◽  
Hodgkin's Lymphomas

Peripheral T-cell lymphoma (PTCL) forms a morphologically heterogeneous group of non-Hodgkin's lymphomas (NHL) with distinct immunophenotypes of mature T cells. Progress has been slow in defining specific clinicopathological entities to this particular group of NHL. In order to elucidate the specific characteristics of PTCL, a direct comparison of PTCL with a group of diffuse B-cell lymphomas (DBCL) was performed. Between June 1983 and December 1987, we studied 114 adults with NHL, using a battery of immunophenotyping markers. Adult T-cell leukemia/lymphoma, lymphoblastic lymphoma, mycosis fungoides/Sézary syndrome, follicular lymphoma, well-differentiated lymphocytic lymphoma, and true histiocytic lymphoma were excluded from this study since these are distinct clinicopathologic entities with well-recognized immunophenotypes. Of the remaining 75 patients, 70 who had adequate clinical information were analyzed, and of these, 34 were PTCL and 36 were DBCL. Classified according to the National Cancer Institute (NCI) Working Formulation (WF), 68% of PTCL and 31% of DBCL were high-grade lymphomas. Clinical and laboratory features were similar, except PTCL had a characteristic skin involvement and tended to present in more advanced stages with more constitutional symptoms. Induction chemotherapy was homogeneous in both groups, and complete remission rates were 62% for PTCL and 67% for DBCL. Patients with DBCL had a better overall survival than patients with PTCL, but the survival benefit disappeared after patients were stratified according to intermediate- or high-grade lymphoma. A subgroup of PTCL patients who had received less intensive induction chemotherapy was found to have a very unfavorable outcome. We conclude that (1) PTCL follows the general grading concept proposed in WF classification; (2) within a given intermediate or high grade, PTCL and DBCL respond comparably to treatment; (3) the intensity of induction chemotherapy has a crucial impact on the outcome of PTCL patients; and (4) with a few exceptions, the clinical and laboratory features of PTCL and DBCL are comparable.

Epstein–Barr virus-associated B-cell lymphoma secondary to FCD-C therapy in patients with peripheral T-cell lymphoma

2008 ◽  
Vol 88 (4) ◽  
pp. 434-440 ◽  
Author(s):  
Katja C. Weisel ◽  
Eckhart Weidmann ◽  
Ioannis Anagnostopoulos ◽  
Lothar Kanz ◽  
Antonio Pezzutto ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Epstein Barr Virus ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma ◽  
Barr Virus ◽  
Epstein Barr

Lymphopenia Predicts Survival in Peripheral T-Cell Lymphoma, Unspecified.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1930-1930
Author(s):  
Brady Beltran ◽  
Domingo Morales ◽  
Pilar Quinones ◽  
Carlos Desposorio ◽  
Eduardo Sotomayor ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
T Cell ◽  
Prognostic Factor ◽  
Lymphocyte Count ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Independent Prognostic Factor ◽  
T Cell Lymphoma ◽  
Peripheral T Cell Lymphoma

Abstract Abstract 1930 Poster Board I-953 Background: Lymphopenia is an independent prognostic factor for survival for different hematological malignancies like follicular lymphoma, Hodgkin lymphoma and diffuse large B-cell lymphoma. The role of lymphopenia at diagnosis on survival in peripheral T-cell lymphoma, unspecified (PTCLU) is not known. Methods: Eighty seven patients with a diagnosis of PTCLU were evaluated at the Edgardo Rebagliati Martins Hospital in Lima, Peru from October 1997 until April 2008. The primary objective of the study was to assess the role of lymphopenia at diagnosis in survival in cases with PTCLU. Lymphocyte count at diagnosis was obtained from the standard complete blood cell count (CBC). Lymphopenia was defined as a lymphocyte count of less than 1 × 109/L. Kaplan-Meier survival estimates and the log-rank test were performed for univariate survival analyses and Cox proportion-hazard regression test was performed for the multivariate analysis. Results: Eighty four patients with a histological diagnosis of PTCLU were included in this study. The median follow-up was 13.4 months (range 1–68 months). The sample population included 54% males and 46% females with a median age of 57 years (range 18–87 years). The median number of lymphocytes at diagnosis was 1.3 × 109/L (range 0.06–5.2 × 109/L). Lymphopenia was present in 37% of cases. In the univariate analysis, lymphopenia was identified as a poor factor for survival (median OS 59 vs. 1 month; p<0.0001). In the multivariate analysis, lymphopenia was compared to the Prognostic Index for PTCLU (PIT) and it remained as an independent predictor for survival (Hazard Ratio 4.8, 95% confidence intervals 2.2–10.6; p<0.0001). Conclusion: This study demonstrates that lymphopenia is an independent prognostic factor for survival in patients with PTCLU, suggesting that the host immune system might play a preponderant role in survival in this group of patients. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Lymphoma of the Uvula: Clinical, Morphological, Histopathological, and Genetic Characterization. A Nationwide Danish Study From 1980 to 2019

2021 ◽  
Vol 8 ◽  
Author(s):  
Lars Iversen ◽  
Patrick Rene Gerhard Eriksen ◽  
Simon Andreasen ◽  
Erik Clasen-Linde ◽  
Preben Homøe ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Marginal Zone ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
B Cell Lymphomas ◽  
Peripheral T Cell Lymphoma ◽  
Presenting Symptoms ◽  
Danish Study

Background: In the head and neck region the uvula is a rare site for extranodal lymphomas to develop. In this national study, we present six cases and provide an overview of the current literature, characterizing the clinical and histopathological features of lymphomas involving this location.Materials and Methods: Clinical information was obtained retrospectively from patient records in a nationwide Danish study covering from 1980 through 2019. In order to validate the diagnoses, uvular tissue specimens were examined histologically and immunohistochemically and if relevant for subtyping, cytogenetic rearrangements were investigated.Results: We present six cases of lymphomas involving the uvula, of which four of the cases were diagnosed with a B-cell lymphoma (two diffuse large B-cell lymphomas, one extranodal marginal zone B-cell lymphoma and one Mantle cell lymphoma), while two were diagnosed with a T-cell lymphoma (one peripheral T-cell lymphoma and one natural killer/T-cell lymphoma). Presenting symptoms included swelling, pain and ulceration of the uvula. Treatment was comprised of radiotherapy and/or chemotherapy, with T-cell lymphomas showing a poorer outcome than B-cell lymphomas.Conclusion: Lymphoma of the uvula is rare, with few case reports being reported in the literature. The most frequent histological subtypes reported are extranodal marginal zone B-cell lymphoma and peripheral T-cell lymphoma. When encountering a swollen, painful and/or ulcerated uvula, the clinician should always consider malignancy as a possible cause. Lymphoma of the uvula is a possible diagnosis and if this is the case, there is a high risk of disseminated disease at the time of diagnosis.

Distribution and influencing factors of tumor mutational burden in different lymphoma subtypes.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e19053-e19053 ◽  
Author(s):  
Hui Zhou ◽  
Xinhua Du ◽  
Tingting Zhao ◽  
Zhou Ouyang ◽  
Wei Liu ◽  
...  
Keyword(s):  
T Cell ◽  
B Cell ◽  
Influencing Factors ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Lymphoma ◽  
Plasma Samples ◽  
Peripheral T Cell Lymphoma ◽  
Mutational Burden ◽  
Tumor Mutational Burden

e19053 Background: Tumor mutational burden (TMB) has emerged as a promising biomarker in melanoma, NSCLC, glioma, and likely across types of solid cancers. However, TMB distribution and influencing factors in non-Hodgkin's lymphoma are still unknown. Methods: In this study, we focused on tumor (tTMB) and peripheral blood TMB (bTMB) in different lymphoma subtypes and conducted a hybridization-capture methodology and targeted 1.1Mb or 1.7 Mb of genomic coding sequence. Analysis of 188 tumors and 98 plasma samples matching oral epithelial normal samples was performed to characterize the landscape of somatic mutations between the TMB high (TMB-H) and TMB low (TMB-L) groups. Results: In our cohort, tTMB and bTMB ranged from 0 to 42.48, and 0.59 to 37.17, respectively. The top quartile TMB distribution (tTMB:12.34, bTMB:13.20) was used as the cut-off value to define TMB-H. DLBCL had significantly higher tTMB than small B cell lymphoma and peripheral T-cell lymphoma (p < 0.0001). 34.09% of DLBCL had TMB-H, and minority of patients had TMB-H in small B cell lymphoma (3.70%), and peripheral T-cell lymphoma (3.85%). The bTMB had the similar distribution to tTMB. Among all the tumor and plasma samples we detected 8 gene mutations having a significant correlation with high TMB including BTG2, PIM1, DUSP2, HIST1H1E, BTG1, SOCS1, HIST1H1C, CD70 ( p< 0.05) . Table TMB distribution of different lymphoma subtypes Conclusions: Compared to other lymphoma subtypes, DLBCL had higher TMB. Particular gene mutation had correlation with high TMB.[Table: see text]

Marqibo (Vincristine Sulfate Liposomes Injection (OPTISOME™) Demonstrates Activity in Patients with Relapsed and Refractory Peripheral T-Cell Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 4466-4466
Author(s):  
M. Alma Rodriguez ◽  
Jane N. Winter ◽  
Biao Lu ◽  
Gary Huang ◽  
Gavin S. Choy ◽  
...  
Keyword(s):  
Adverse Event ◽  
T Cell ◽  
Cell Lymphoma ◽  
International Workshop ◽  
Objective Response ◽  
Complete Response ◽  
T Cell Lymphoma ◽  
Low Grade ◽  
Peripheral T Cell Lymphoma ◽  
Best Response

Abstract Introduction: New and more effective agents are needed to improve treatment outcomes for patients with relapsed and refractory peripheral T-cell lymphoma (PTCL). Marqibo is a novel formulation of vincristine (VCR) encapsulated in sphingomyelin/cholesterol liposome called OPTISOME. In preclinical studies, OPTISOME technology has been shown to provide targeted, increased, and sustained delivery of VCR to tumor cells compared to non-encapsulated VCR or VCR encapsulated in conventional liposomes. Methods: PTCL patients from two multi-center phase 2 studies of Marqibo in relapsed and refractory lymphoid malignancies are integrated for safety and efficacy evaluation. In both studies, Marqibo (2.0 mg/m2 without dose capping IV over 60 minutes) was administered every 14 days for up to 12 cycles or until toxicity or progressive disease was observed. The primary efficacy endpoint of the 2 studies was the objective response rate (ORR) defined as the percentage of patients whose best response was complete response (CR), complete response unconfirmed, or partial response (PR). Best response was determined according to the International Workshop Response Criteria. Secondary endpoints included adverse event evaluation, time to progression (TTP) and overall survival (OS). Results: Six (3M/3F) patients diagnosed with PTCL received at least one dose of Marqibo. At baseline, the median age was 59 years (range, 34–86). All six patients had aggressive disease and most were heavily pretreated. The median number of prior lines of chemotherapy and immunotherapy regimens was 3 (range, 1–6) and four patients (66.7%) had received prior autologous bone marrow transplant. All patients had prior exposure to neurotoxic therapy: platinum compounds (33.3%), taxanes (16.7%) and VCR (100%). All patients had achieved a CR or PR to their frontline therapy and 50% (3/6) had achieved a CR or PR to their last line of therapy prior to receiving Marqibo. Patients received a median of 4 cycles of Marqibo (range, 1–9). Median cumulative dose of Marqibo was 7 mg/m2 (range, 2–17.4). The most commonly reported adverse event was peripheral sensory neuropathy (3 of 6 patients) and all of Grade 1 severity. Three patients had PR, 1 patient had stable disease, 1 patient experienced disease progression, and 1 patient was unevaluable. Median OS and TTP were 194 and 70 days, respectively. Conclusions: These preliminary results suggest encouraging activity and tolerability of Marqibo in heavily pre-treated relapsed and refractory PTCL patients. Given the high proportion of exposure to neurotoxic agents preceding Marqibo, the low grade neurotoxicity noted following Marqibo is a favorable finding.

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