Synergy of BCL2 and histone deacetylase inhibition against leukemic cells from cutaneous T-cell lymphoma patients

The presence and degree of peripheral blood involvement in patients with cutaneous T-cell lymphoma (CTCL) portend a worse clinical outcome. Available systemic therapies for CTCL may variably decrease tumor burden and improve quality of life, but offer limited effects on survival; thus, novel approaches to the treatment of advanced stages of this non-Hodgkin lymphoma are clearly warranted. Mutational analyses of CTCL patient peripheral blood malignant cell samples suggested the antiapoptotic mediator B-cell lymphoma 2 (BCL2) as a potential therapeutic target. To test this, we developed a screening assay for evaluating the sensitivity of CTCL cells to targeted molecular agents, and compared a novel BCL2 inhibitor, venetoclax, alone and in combination with a histone deacetylase (HDAC) inhibitor, vorinostat or romidepsin. Peripheral blood CTCL malignant cells were isolated from 25 patients and exposed ex vivo to the 3 drugs alone and in combination, and comparisons were made to 4 CTCL cell lines (Hut78, Sez4, HH, MyLa). The majority of CTCL patient samples were sensitive to venetoclax, and BCL2 expression levels were negatively correlated (r = –0.52; P = .018) to 50% inhibitory concentration values. Furthermore, this anti-BCL2 effect was markedly potentiated by concurrent HDAC inhibition with 93% of samples treated with venetoclax and vorinostat and 73% of samples treated with venetoclax and romidepsin showing synergistic effects. These data strongly suggest that concurrent...
Source: Blood - Category: Hematology Authors: Tags: Lymphoid Neoplasia Source Type: research

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CONCLUSIONS: SS-associated T cell lymphomas constitute a minority. Treatment with anti-CD20 monoclonal antibody (mAb) and viral infections may be implicated in their pathogenesis. PMID: 33025901 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Rheumatology - Category: Rheumatology Tags: Clin Exp Rheumatol Source Type: research
Discussion In this section, we discuss the mechanisms responsible for lymphomagenesis in the various inborn errors of immunity and provide an overview of the treatment. Defects in Immune Responses That Predispose to Lymphomagenesis in PIDDs The complex immune mechanisms and their interplay that predisposes to neoplastic transformation of B or T cells and development of lymphomas in PIDD patients has not been fully elucidated. However, it is expected that the etiology in most cases is multifactorial and related to a dynamic regulation of immune response and environmental triggers (Figure 3). An underlying intrinsic susce...
Source: Frontiers in Immunology - Category: Allergy & Immunology Source Type: research
Conclusions: In pts with R/R NHL, active doses of Cami-T with acceptable safety profiles were identified for both B-cell and T-cell lymphoma during dose escalation of this study. Five out of the 10 pts on study with T-cell lymphoma treated in the 60, 80, or 100 µg/kg cohorts responded. Subtype-specific cohorts in the dose escalation portion of this study are underway to better define the recommended dose for expansion.Study sponsored by ADC Therapeutics. MSD: Consultancy, Honoraria; ADC Therapeutics: Consultancy, Honoraria, Research Funding; Roche: Consul...
Source: Blood - Category: Hematology Authors: Tags: 624. Hodgkin Lymphoma and T/NK Cell Lymphoma-Clinical Studies: Poster I Source Type: research
CONCLUSIONS: This is the first study evaluating the safety and efficacy of the BET inhibitor molibresib in NHL subjects. Overall, thrombocytopenia and other AEs were monitorable, manageable and reversible. The RP2D was identified as 60 mg QD. Single-agent activity was observed across multiple NHL subtypes at both 60 mg and 80 mg doses; most notable was a 50% response rate in subjects with CTCL. Because of the promising data, Part 2 of the BET116183 study is currently open and enrolling subjects with CTCL to better define the clinical activity of BET bromodomain inhibition in this histology.DisclosuresDickinson: GSK: Consul...
Source: Blood - Category: Hematology Authors: Tags: 626. Aggressive Lymphoma (Diffuse Large B-Cell and Other Aggressive B-Cell Non-Hodgkin Lymphomas)-Results from Prospective Clinical Trials: Poster I Source Type: research
Primary cutaneous lymphomas are a heterogeneous group of lymphoid malignancies and are the second most common group of extranodal non-Hodgkin lymphoma (NHL) following gastrointestinal lymphomas.1 NHL involving the female genitalia is unusual, posing diagnostic and therapeutic challenges.2-4 Rare cases of vulvar NHL presenting as a vulvar mass were mostly diagnosed as diffuse large B-cell lymphoma and had an aggressive course.3,5 Cases of cutaneous T-cell lymphoma (CTCL) involving the vulva have been rarely reported.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Case Report Source Type: research
CONCLUSION: In this study, weekly administration of clofarabine was demonstrated to be safe and associated with minimal hematologic toxicity at doses ranging from 10-40 mg/m2. In prior studies when dosed daily for 5 consecutive days, the MTD was shown to be 4 mg/m2. Weekly dosing within this dose range did not result in dose modifications, and the MTD was not reached. Clinical efficacy was observed in one patient with CTCL who was treated in the lowest-dose cohort. PMID: 29438091 [PubMed - as supplied by publisher]
Source: The Oncologist - Category: Cancer & Oncology Authors: Tags: Oncologist Source Type: research
This article is protected by copyright. All rights reserved. PMID: 28301708 [PubMed - as supplied by publisher]
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
Total skin electron beam therapy (TSEB) is an integral treatment modality in primary cutaneous T-cell lymphoma (pCTCL), a type of non-Hodgkin lymphoma.
Source: Clinical Lymphoma, Myeloma and Leukemia - Category: Hematology Authors: Tags: Non-Hodgkin Lymphoma Source Type: research
Conclusion Alisertib has antitumor activity in PTCL, including heavily pretreated patients. These promising results are being further investigated in an ongoing international, randomized phase III trial comparing alisertib with investigator's choice in PTCL.
Source: Journal of Clinical Oncology - Category: Cancer & Oncology Authors: Tags: Biologic Therapy, Translational Oncology Hematologic Malignancy Source Type: research
Abstract Non-Hodgkin lymphoma is a heterogeneous group of lymphoproliferative disorders(1) accounting for
Source: The British Journal of Dermatology - Category: Dermatology Authors: Tags: Br J Dermatol Source Type: research
More News: Cancer & Oncology | Cutaneous T cell lymphoma | Genetics | Leukemia | Lymphoma | Non-Hodgkin's Lymphoma | T-cell Lymphoma