^
    1d
    Romidepsin and Parsaclisib for the Treatment of Relapsed or Refractory T-Cell Lymphomas (clinicaltrials.gov)
    P1, N=5, Active, not recruiting, Walter Hanel | Recruiting --> Active, not recruiting | N=20 --> 5 | Trial primary completion date: Dec 2023 --> Dec 2024
    Enrollment closed • Enrollment change • Trial primary completion date • Combination therapy
    |
    TNFRSF8 (TNF Receptor Superfamily Member 8)
    |
    TNFRSF8 positive
    |
    Istodax (romidepsin) • parsaclisib (INCB50465)
    8d
    Exploring the role of histone deacetylase and histone deacetylase inhibitors in the context of multiple myeloma: mechanisms, therapeutic implications, and future perspectives. (PubMed, Exp Hematol Oncol)
    Four drugs in this category have received approval from the U.S. Food and Drug Administration (FDA) for use: Panobinonstat (though canceled by the FDA in 2022), Vorinostat, Belinostat and Romidepsin. This review provides a comprehensive evaluation of the clinical efficacy and safety data pertaining to the currently approved histone deacetylase inhibitors, as well as an explanation of the crucial function of histone deacetylase in multiple myeloma and the characteristics of the different histone deacetylase inhibitors. Moreover, it provides a concise overview of the most recent developments in the use of histone deacetylase inhibitors for treating multiple myeloma, as well as potential future uses in treatment.
    Review • Journal • Epigenetic controller
    |
    BCL2 (B-cell CLL/lymphoma 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • HSP90AA1 (Heat Shock Protein 90 Alpha Family Class A Member 1Heat Shock Protein 90 Alpha Family Class A Member 1)
    |
    Zolinza (vorinostat) • Istodax (romidepsin) • Beleodaq (belinostat)
    22d
    RV-CL-PTCL-PI-003974: Romidepsin and Lenalidomide in Treating Patients With Previously Untreated Peripheral T-Cell Lymphoma (clinicaltrials.gov)
    P2, N=30, Active, not recruiting, Northwestern University | Trial completion date: Aug 2023 --> Aug 2024
    Trial completion date
    |
    ALK (Anaplastic lymphoma kinase) • CD20 (Membrane Spanning 4-Domains A1) • CD8 (cluster of differentiation 8) • TNFRSF8 (TNF Receptor Superfamily Member 8) • PAX5 (Paired Box 5) • CD4 (CD4 Molecule) • NCAM1 (Neural cell adhesion molecule 1) • CD5 (CD5 Molecule) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • GZMB (Granzyme B) • MME (Membrane Metalloendopeptidase) • CD7 (CD7 Molecule) • UBR5 (Ubiquitin Protein Ligase E3 Component N-Recognin 5)
    |
    ALK negative
    |
    lenalidomide • Istodax (romidepsin)
    1m
    Synergistic integration of histone deacetylase inhibitors apparently enhances the cytokine-induced killer cell efficiency in multiple myeloma via the NKG2D pathway. (PubMed, Clin Transl Immunology)
    We examined clinically relevant HDACis (panobinostat/LBH589 and romidepsin) alongside CIK cells derived from peripheral blood mononuclear cells across diverse MM cell lines (U266, RPMI8226, OPM-2 and NCI-H929). Our analyses provide sufficient evidence to consider this clinically forgotten instance (HDACis-CIK cell combination) as a therapeutic priority for MM treatment. Furthermore, we suggest that NKG2D/NKG2D-ligand interactions activating NK/NKT cells may contribute to enhanced myeloma cell lysis in response to HDACis treatment by CIK cells.
    Journal • IO biomarker • Epigenetic controller
    |
    IFNG (Interferon, gamma) • GZMB (Granzyme B) • MICA (MHC Class I Polypeptide-Related Sequence A) • MICB (MHC Class I Polypeptide-Related Sequence B) • NKG2D (killer cell lectin like receptor K1) • ULBP2 (UL16 Binding Protein 2)
    |
    Farydak (panobinostat) • Istodax (romidepsin)
    1m
    Epigenetic small-molecule screen for inhibition and reversal of acinar ductal metaplasia in mouse pancreatic organoids. (PubMed, Front Pharmacol)
    We developed a novel morphology-based screen using organoids from wildtype and p48Cre/+ (Cre) mice to discover epigenetic modulators that inhibit or reverse pancreatic ADM more effectively than the broad-spectrum HDAC inhibitor trichostatin A (TSA)...The class I HDAC inhibitors apicidin and FK228, and the histone methyltransferase inhibitor chaetocin demonstrated pronounced ADM inhibition and reversal without inducing significant cytotoxicity at 1 µM...RNA-sequencing indicated that angiotensinogen was the top inhibited pathway during ADM reversal. Our findings demonstrate a unique epigenetic mechanism and suggest that the phenotypic screen developed here may be applied to discover potential treatments for PDAC.
    Preclinical • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS G12D • KRAS G12
    |
    Istodax (romidepsin) • trichostatin A (VTR-297)
    2ms
    Oracle: Efficacy and Safety of Oral Azacitidine Compared to Investigator's Choice Therapy in Patients With Relapsed or Refractory AITL (clinicaltrials.gov)
    P3, N=86, Active, not recruiting, The Lymphoma Academic Research Organisation | Trial completion date: Feb 2024 --> Jun 2024
    Trial completion date
    |
    PD-1 (Programmed cell death 1) • BCL6 (B-cell CLL/lymphoma 6) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • ICOS (Inducible T Cell Costimulator) • MME (Membrane Metalloendopeptidase)
    |
    PD-1 expression
    |
    gemcitabine • bendamustine • Istodax (romidepsin) • Onureg (azacitidine oral)
    2ms
    Romidepsin exhibits anti-esophageal squamous cell carcinoma activity through the DDIT4-mTORC1 pathway. (PubMed, Cancer Gene Ther)
    Furthermore, romidepsin exhibited better efficacy and safety compared to the conventional therapeutic drugs in ESCC patient-derived xenografted (PDX) mouse models. These data indicate that romidepsin may be a novel option for anti-ESCC therapy.
    Journal
    |
    DDIT4 (DNA Damage Inducible Transcript 4)
    |
    Istodax (romidepsin)
    2ms
    Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone: NCC-GCTB8-C1 and NCC-GCTB9-C1. (PubMed, Hum Cell)
    Among the 214 antitumor agents tested, romidepsin, a histone deacetylase inhibitor, and mitoxantrone, a topoisomerase inhibitor, were identified as potential therapeutic agents against GCTB. Conclusively, the establishment of NCC-GCTB8-C1 and NCC-GCTB9-C1 provides novel and crucial resources that are expected to advance GCTB research and potentially revolutionize treatment strategies.
    Preclinical • Journal
    |
    H3-3A (H3.3 Histone A)
    |
    mitoxantrone • Istodax (romidepsin)
    2ms
    Romidepsin in Treating Patients With Lymphoma, Chronic Lymphocytic Leukemia, or Solid Tumors With Liver Dysfunction (clinicaltrials.gov)
    P1, N=37, Active, not recruiting, National Cancer Institute (NCI)
    Trial completion date
    |
    ER (Estrogen receptor) • AFP (Alpha-fetoprotein)
    |
    Istodax (romidepsin)
    2ms
    Romidepsin, CC-486 (5-azacitidine), Dexamethasone, and Lenalidomide (RAdR) for Relapsed/Refractory T-cell Malignancies (clinicaltrials.gov)
    P1, N=20, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting | N=30 --> 20
    Enrollment closed • Enrollment change
    |
    TNFRSF8 positive
    |
    lenalidomide • Istodax (romidepsin) • Onureg (azacitidine oral)
    4ms
    The methyltransferases METTL7A and METTL7B confer resistance to thiol-based histone deacetylase inhibitors. (PubMed, Mol Cancer Ther)
    To identify alternative mechanisms of resistance to romidepsin, we selected MCF-7 breast cancer cells with romidepsin in the presence of the P-gp inhibitor verapamil to reduce the likelihood of P-gp-mediated resistance. The resulting cell line, MCF-7 DpVp300, does not express P-gp and was found to be selectively resistant to romidepsin but not to other HDACis such as belinostat, panobinostat, or vorinostat. RNA sequencing analysis revealed upregulation of the mRNA coding for the putative methyltransferase, METTL7A, whose paralog, METTL7B, was previously shown to methylate thiol groups on hydrogen sulfide and captopril...We demonstrate that expression of METTL7A or METTL7B confers resistance to thiol-based HDACis and that both enzymes are capable of methylating thiol-containing HDACis. We thus propose that METTL7A and METTL7B confer resistance to thiol-based HDACis by methylating and inactivating the zinc-binding thiol.
    Journal • Epigenetic controller
    |
    ABCB1 (ATP Binding Cassette Subfamily B Member 1)
    |
    ABCB1 expression
    |
    Zolinza (vorinostat) • Farydak (panobinostat) • Istodax (romidepsin) • Beleodaq (belinostat) • captopril
    5ms
    Modulation of Expression of Drug Metabolizing Enzymes and Augmentation of Anti-cancer Drug Effects: Through Epigenetics and Three-dimensional Cancer Cell Culture Systems (PubMed, Yakugaku Zasshi)
    Additionally, I have been investigating methods to enhance the anti-tumor effects of irinotecan (CPT-11) and 5-fluorouracil (5-FU) using epigenetic modifying inhibitors of DNA methyltransferase and histone deacetylase...Furthermore, the administration of DAC and the histone deacetylase inhibitor depsipeptide [(DEP), an anti-cancer drug romidepsin] significantly increased the cellular sensitivities of human colon cancer cells to CPT-11 and 5-FU, respectively...Another facet of my research is centered around understanding the gene regulatory mechanisms of the CYP1 family through aryl hydrocarbon receptors (AhR)s under glucose-deprivation stress and in three-dimensional (3D) culture systems of human solid tumor cells. In the 3D culture of human liver cancer cells, I found Pregnane X Receptor being implicated in the regulation of CYP1A2, which aligns with the in vivo mode of CYP1A2 expression.
    Preclinical • Journal • IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • HLA-DRB1 (Major Histocompatibility Complex, Class II, DR Beta 1) • CYP1A2 (Cytochrome P450, family 1, subfamily A, polypeptide 2) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • CYP3A4 (Cytochrome P450, family 3, subfamily A, polypeptide 4) • CYP1B1 (Cytochrome P450 Family 1 Subfamily B Member 1)
    |
    5-fluorouracil • irinotecan • Istodax (romidepsin)
    5ms
    ISTODAX® for Intravenous Infusion Drug Use Results Survey- Relapsed or Refractory Peripheral T-Cell Lymphoma (clinicaltrials.gov)
    P=N/A, N=150, Completed, Celgene | Recruiting --> Completed | Trial completion date: Apr 2023 --> Oct 2023 | Trial primary completion date: Apr 2023 --> Oct 2023
    Trial completion • Trial completion date • Trial primary completion date
    |
    Istodax (romidepsin)
    6ms
    CELL-FREE DNA IN PERIPHERAL T-CELL LYMPHOMAS: PRELIMINARY DATA FROM THE PHASE IB/II PTCL13 STUDY (SIE 2023)
    The prospective Phase Ib/II PTCL13 trial tested the combination of Romidepsin with chemotherapy in patients (pts) with newly diagnosed Peripheral T-cell Lymphoma (PTCL), but it failed to improve survival...Elevated cfDNA levels before treatment is associated with high-risk features and worse survival. Liquid biopsy is feasible in PTCLs and allow to detect residual disease during treatment, which is associated with disease progression.
    P1/2 data • Cell-free DNA
    |
    TP53 (Tumor protein P53)
    |
    TP53 mutation
    |
    Istodax (romidepsin)
    6ms
    Suppression of GATA2/3-FOXA1-HER3 Axis by Histone Deacetylase (HDAC) Inhibitors shows Antitumor Activity in Basal-like Breast Cancer (SABCS 2023)
    We recently found that panobinostat and romidepsin potently induced TNBC cell growth inhibition and apoptosis via downregulation of HER3 through suppression of forkhead box protein A1 (FOXA1), a pioneering transcription factor...Notably, the combination of HDACis with an EGFR inhibitor (gefitinib) or an anti-HER3 antibody synergistically enhanced the anti-survival effects on BLBC cells... HDACis exhibit potent inhibitory effects on BLBC cells via downregulation of GATA2/3-mediated repression of FOXA1 gene transcription, which in turn suppresses HER3 expression and signaling. Our findings indicate that epigenetic targeting of the GATA2/3-FOXA1-HER3 axis may be an effective therapeutic strategy for the eradication of BLBC tumors.
    Epigenetic controller
    |
    ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • FOXA1 (Forkhead Box A1) • GATA2 (GATA Binding Protein 2)
    |
    ERBB3 expression
    |
    gefitinib • Farydak (panobinostat) • Istodax (romidepsin)
    6ms
    First-in-Class HAT Activator (YF2) Combined with JAK/STAT Inhibitor (ruxolitinib) Unveils Potential Novel Treatment Approach for HDAC Inhibitor-Resistant CTCL (ASH 2023)
    In addition, we generated a belinostat-resistant H9 cell line (H9-belino-R) by incrementally exposing H9 to increasing concentrations of belinostat...H9-belino-R retained significant resistance to other HDAC inhibitors such as romidepsin [(H9: IC50 = 0.97nM (SEM ± 0.030), H9-belino-R: IC50 = 1.38nM (SEM ± 0.028)] and panobinostat [H9: IC50 = 3.11nM (SEM ± 0.19), H9-belino-R: IC50 = 9.00nM (SEM ± 1.55)] as measured by the CellTiter-Glo Viability Assay...These preliminary findings provide us with evidence that suggests that the combination of YF2 and ruxolitinib can serve as a novel treatment combination for CTCL. Further study is planned to explore this treatment in murine models of disease.
    IO biomarker
    |
    BCL2 (B-cell CLL/lymphoma 2) • BCL2L1 (BCL2-like 1) • JAK1 (Janus Kinase 1) • ANXA5 (Annexin A5) • BAK1 (BCL2 Antagonist/Killer 1)
    |
    JAK1 mutation
    |
    Jakafi (ruxolitinib) • Farydak (panobinostat) • Istodax (romidepsin) • YF2 • Beleodaq (belinostat)
    6ms
    Romidepsin in Combination With Lenalidomide in Adults With Relapsed or Refractory Lymphomas and Myeloma (clinicaltrials.gov)
    P1/2, N=62, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed
    Trial completion • Combination therapy
    |
    lenalidomide • Istodax (romidepsin)
    7ms
    NCI-2018-00810: Venetoclax and Romidepsin in Treating Patients With Recurrent or Refractory Mature T-Cell Lymphoma (clinicaltrials.gov)
    P2, N=12, Completed, City of Hope Medical Center | Active, not recruiting --> Completed
    Trial completion
    |
    BCL2 (B-cell CLL/lymphoma 2)
    |
    Venclexta (venetoclax) • Istodax (romidepsin)
    7ms
    Identification of druggable genes for multiple myeloma based on genomic information. (PubMed, Genomics Inform)
    Notably, only one of these 10 drugs, panobinostat, has been approved for use in MM. The two most promising genes, calcium signal-modulating cyclophilin ligand (CAMLG) and histone deacetylase 2 (HDAC2), were targeted by four drugs (cyclosporine, belinostat, vorinostat, and romidepsin), all of which have clinical evidence supporting their use in the treatment of MM. Interestingly, five of the 10 drugs have been approved for other indications than MM, but they may also be effective in treating MM. Therefore, this study aimed to clarify the genomic variants involved in the pathogenesis of MM and highlight the potential benefits of these genomic variants in drug discovery.
    Journal
    |
    HDAC2 (Histone deacetylase 2)
    |
    Zolinza (vorinostat) • Farydak (panobinostat) • Istodax (romidepsin) • Beleodaq (belinostat)
    8ms
    Therapeutic HDAC inhibition in hypermutant diffuse intrinsic pontine glioma. (PubMed, Neoplasia)
    We screened PBT-24FH cells for sensitivity to a panel of HDAC inhibitors (HDACis) in vitro, identifying two HDACis associated with low nanomolar IC50s, quisinostat (27 nM) and romidepsin (2 nM). Here, we establish the preclinical efficacy of quisinostat against hypermutant DIPG, supporting further investigation of epigenetic targeting of hypermutant pediatric cancers with the potential for clinical translation. These findings support further investigation of HDAC inhibitors against pontine high-grade gliomas, beyond only those with histone mutations, as well as against other hypermutant central nervous system tumors.
    Journal
    |
    Istodax (romidepsin) • quisinostat (JNJ 26481585)
    9ms
    Recent histone deacetylase inhibitors in cancer therapy. (PubMed, Cancer)
    Several HDACi drugs like vorinostat, romidepsin, panobinostat, and belinostat are approved by the Food and Drug Administration. China and Japan have approved the use of tucidinostat, a new subtype-selective HDACi that inhibits class 1 HDAC1, HDAC2, HDAC3, as well as class 2b HDAC10...This review highlights the HDACi classes, the mechanism of action of these inhibitors, their preclinical and clinical efficacy, and the latest clinical trials and patents used in cancer therapeutics. Overall, this review focuses on patents and clinical trials data from 2019 onward to give a better viewpoint on current trends in HDACis as chemotherapy agents.
    Review • Journal • Epigenetic controller
    |
    HDAC2 (Histone deacetylase 2) • HDAC10 (Histone Deacetylase 10) • HDAC3 (Histone Deacetylase 3)
    |
    Epidaza (chidamide) • Zolinza (vorinostat) • Farydak (panobinostat) • Istodax (romidepsin) • Beleodaq (belinostat)
    9ms
    Update on histone deacetylase inhibitors in peripheral T-cell lymphoma (PTCL). (PubMed, Clin Epigenetics)
    Several HDACis, such as romidepsin, belinostat, and chidamide, have demonstrated favorable clinical efficacy and safety in PTCLs. Mutation analysis based on next-generation sequencing may advance our understanding of the correlation between epigenetic mutation profiles and relevant targeted therapies. Multitargeted HDACis and HDACi-based prodrugs hold promising futures and offer further directions for drug design.
    Review • Journal • Epigenetic controller
    |
    Epidaza (chidamide) • Istodax (romidepsin) • Beleodaq (belinostat)
    9ms
    Establishment and characterization of two novel patient-derived cell lines from giant cell tumor of bone. (PubMed, Hum Cell)
    We identified histone deacetylase inhibitor romidepsin as a possible treatment for GCTB. These findings suggest that NCC-GCTB6-C1 and NCC-GCTB7-C1 could be valuable tools for preclinical and basic research on GCTB.
    Preclinical • Journal
    |
    H3-3A (H3.3 Histone A)
    |
    Istodax (romidepsin)
    9ms
    Establishment and characterization of NCC-DFSP4-C1: a novel cell line from a patient with dermatofibrosarcoma protuberans having the fibrosarcomatous transformation. (PubMed, Hum Cell)
    Although imatinib, a PDGF receptor inhibitor, is a potent therapeutic agent for classic DFSP, it is less effective for DFSP with fibrosarcomatous transformation. By screening a drug library, we found that bortezomib and romidepsin demonstrated the strongest suppressive effects on the proliferation of NCC-DFSP4-C1 cells. In conclusion, we report a novel cell line of DFSP with fibrosarcomatous transformation, and demonstrate its utility in the development of novel therapeutic agents for DFSP.
    Preclinical • Journal
    |
    COL1A1 (Collagen Type I Alpha 1 Chain) • PDGFB (Platelet Derived Growth Factor Subunit B)
    |
    COL1A1-PDGFB fusion
    |
    imatinib • bortezomib • Istodax (romidepsin)
    10ms
    Reversing vemurafenib-resistance in primary melanoma cells by combined romidepsin and type I IFN treatment through blocking of tumorigenic signals and induction of immunogenic effects. (PubMed, Int J Cancer)
    Moreover, the immunogenic potential of drug-treated VEM-resistant melanoma cells results significantly enhanced, given the increased phagocytosis rate of these cells by dendritic cells, which in turn exhibit also a selective down-modulation of the immune checkpoint TIM-3. Overall, our results provide evidence that combined epigenetic-immune drugs can overcome VEM resistance of primary melanoma cells by oncogenic and immune pathways reprogramming, and pave the way for rapidly exploiting this combination to improve BRAFi-resistant metastatic melanoma treatment, also via reinforcement of immune checkpoint inhibitor therapy.
    Journal • IO biomarker
    |
    BRAF (B-raf proto-oncogene) • AXL (AXL Receptor Tyrosine Kinase) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • IFNA1 (Interferon Alpha 1) • MITF (Melanocyte Inducing Transcription Factor)
    |
    BRAF mutation • AXL expression
    |
    Zelboraf (vemurafenib) • Istodax (romidepsin)
    10ms
    Integrated multiomics analysis and machine learning refine molecular subtypes and prognosis for muscle-invasive urothelial cancer. (PubMed, Mol Ther Nucleic Acids)
    The high-CMLS group had a poor prognosis and lower likelihood of benefitting from immunotherapy, but dasatinib and romidepsin may serve as promising treatments for them. Comprehensive analysis of multiomics data can offer important insights and further refine the molecular classification of MUC. Identification of CMLS represents a valuable tool for early prediction of patient prognosis and for screening potential candidates likely to benefit from immunotherapy, with broad implications for clinical practice.
    Journal • Machine learning
    |
    dasatinib • Istodax (romidepsin)
    10ms
    Safety and efficacy of tenalisib in combination with romidepsin in patients with relapsed/refractory T-cell lymphoma: results from a phase I/II open-label multicenter study. (PubMed, Haematologica)
    Coadministration of tenalisib and romidepsin did not significantly alter the pharmacokinetics of romidepsin. Overall, tenalisib and romidepsin combination demonstrated a favorable safety and efficacy profile supporting its further development for relapsed/refractory TCL.
    Clinical • P1/2 data • Journal • Combination therapy
    |
    Istodax (romidepsin) • tenalisib (RP6530)
    10ms
    A Phase 2 Multicenter Study of High Dose Chemotherapy With Autologous Stem Cell Transplant Followed by Maintenance Therapy With Romidepsin for the Treatment of T Cell Non-Hodgkin Lymphoma (clinicaltrials.gov)
    P2, N=47, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Trial completion date: Jul 2023 --> Jul 2024 | Trial primary completion date: Jul 2023 --> Jul 2024
    Trial completion date • Trial primary completion date
    |
    CD34 (CD34 molecule)
    |
    cytarabine • etoposide IV • carmustine • Istodax (romidepsin) • melphalan
    10ms
    Efficacy and safety of histone deacetylase inhibitors in peripheral T-cell lymphoma: a systematic review and meta-analysis on prospective clinical trials. (PubMed, Front Oncol)
    In addition, the pooled CR rate was 17% (95% CI, 13-22%), 10% (95% CI, 5-15%), and 10% (95% CI, 5-15%) in the romidepsin, belinostat, and chidamide monotherapy subgroups, respectively. The combination of HDAC inhibitor and chemotherapy exhibited superior efficacy to HDAC inhibitor monotherapy in the R/R PTCL setting. Additionally, HDAC inhibitor-based therapy had higher efficacy in angioimmunoblastic T-cell lymphoma patients than that in other subtypes.
    Retrospective data • Review • Epigenetic controller
    |
    Epidaza (chidamide) • Istodax (romidepsin) • Beleodaq (belinostat)
    10ms
    Histone Deacetylase Inhibition and Autophagy Modulation Induces a Synergistic Antiproliferative Effect and Cell Death in Cholangiocarcinoma Cells. (PubMed, ACS Omega)
    HDAC inhibitors, MS-275 and romidepsin, showed a better synergistic effect with the nocodazole combination. While acetylation levels were increased in response to HDAC inhibitors and autophagy modulator combinations, the HDAC expression decreased. This study highlights the importance of the combination of HDAC inhibition and autophagy modulators and demonstrates a synergistic effect, which could be a promising therapy and novel treatment approach for cholangiocarcinoma.
    Journal • Epigenetic controller
    |
    ANXA5 (Annexin A5)
    |
    Istodax (romidepsin) • Jingzhuda (entinostat)
    11ms
    Tailoring Therapy In PTCL (SOHO 2023)
    There are several approved agents for the treatment of relapsed T-cell lymphomas including pralatrexate, romidepsin, belinostat, and brentuximab vedotin, but none of them are considered curative. As these studies mature, it is expected that the treatment for TCL will evolve so that each individual patient will be treated based on the biologic and molecular characteristics of their tumor type. The future for TCL remains promising.
    IO biomarker
    |
    ALK (Anaplastic lymphoma kinase) • TNFRSF8 (TNF Receptor Superfamily Member 8) • TET2 (Tet Methylcytosine Dioxygenase 2) • CCR4 (C-C Motif Chemokine Receptor 4) • IL2RA (Interleukin 2 receptor, alpha) • CD70 (CD70 Molecule) • RHOA (Ras homolog family member A) • SYK (Spleen tyrosine kinase) • TBX21 (T-Box Transcription Factor 21) • TP63 (Tumor protein 63) • DUSP22 (Dual Specificity Phosphatase 22) • USP22 (Ubiquitin Specific Peptidase 22) • SIRPA (Signal Regulatory Protein Alpha)
    |
    TET2 mutation • TNFRSF8 expression
    |
    Adcetris (brentuximab vedotin) • Istodax (romidepsin) • Beleodaq (belinostat) • Folotyn (pralatrexate)
    11ms
    New Insights Into the Pathogenesis of T-Cell Lymphoma and How This May Guide Treatment (SOHO 2023)
    TFHLs, which frequently carry mutations of TET2, DNMT3A, RHOA and IDH2, rarely seen in combination in other PTCL, have a higher response rate to hypomethylating agents such as 5-azacytidine and histone deacetylase inhibitors such as romidepsin. Tumors harboring SVs or amplification of CD274 may show greater sensitivity to immune checkpoint inhibitors. Four tumor microenvironment subgroups defined by expression profiling alone, may represent immunotherapy biomarkers.
    PD(L)-1 Biomarker • IO biomarker
    |
    PD-L1 (Programmed death ligand 1) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RB1 (RB Transcriptional Corepressor 1) • NOTCH1 (Notch 1) • JAK2 (Janus kinase 2) • TET2 (Tet Methylcytosine Dioxygenase 2) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • JAK1 (Janus Kinase 1) • HAVCR2 (Hepatitis A Virus Cellular Receptor 2) • STAT3 (Signal Transducer And Activator Of Transcription 3) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • CD4 (CD4 Molecule) • JAK3 (Janus Kinase 3) • RHOA (Ras homolog family member A) • STAT5B (Signal Transducer And Activator Of Transcription 5B) • TBX21 (T-Box Transcription Factor 21) • TYK2 (Tyrosine Kinase 2) • DUSP22 (Dual Specificity Phosphatase 22) • GATA3 (GATA binding protein 3) • USP22 (Ubiquitin Specific Peptidase 22)
    |
    PD-L1 expression • TP53 mutation • ALK positive • DNMT3A mutation • ALK fusion • NOTCH1 mutation • CDKN2A deletion • TET2 mutation • CDKN2A mutation • RB1 deletion • PD-L1 amplification • ALK negative • STAT3 mutation
    |
    azacitidine • Istodax (romidepsin)
    11ms
    Multicenter phase 2 study of romidepsin plus lenalidomide for previously untreated peripheral T-cell lymphoma. (PubMed, Blood Adv)
    The estimated 1-yr PFS was 48.6% with 2-yr PFS at 31.5%, and the estimated 1-yr OS was 71.1% with 2-yr OS at 49.5%. This study provides the first demonstration that the chemotherapy-free biologic combination of romidepsin and lenalidomide is feasible and effective as initial therapy for PTCL and warrants further evaluation.
    P2 data • Journal
    |
    lenalidomide • Istodax (romidepsin)
    12ms
    Direct Tumor Microinjection and FDG-PET in Testing Drug Sensitivity in Patients With Relapsed or Refractory Non-Hodgkin Lymphoma, Hodgkin Lymphoma, or Stage IV Breast Cancer (clinicaltrials.gov)
    P1, N=39, Suspended, Mayo Clinic | Trial completion date: May 2023 --> May 2026 | Trial primary completion date: Apr 2023 --> Apr 2025
    Trial completion date • Trial primary completion date • FDG PET • Metastases
    |
    Keytruda (pembrolizumab) • Opdivo (nivolumab) • gemcitabine • Rituxan (rituximab) • Gazyva (obinutuzumab) • Aliqopa (copanlisib) • Darzalex (daratumumab) • Herzuma (trastuzumab-pkrb) • carfilzomib • Istodax (romidepsin) • Trazimera (trastuzumab-qyyp) • Beleodaq (belinostat)
    12ms
    REAL-WORLD TREATMENT PATTERNS AND ADVERSE EVENTS AMONG PATIENTS WITH PERIPHERAL T-CELL LYMPHOMA: A RETROSPECTIVE DATABASE STUDY (EHA 2023)
    The most common treatment regimens in the 1LOT were CHOP/CHOP-like, CHOEP/CHOEP-like, and brentuximab vedotin, in the 2LOT were monotherapies (e.g., romidepsin), and in ≥3LOT was brentuximab vedotin (Table 1)...In the 1LOT regimen, patients on combination therapies, such as CHOP/CHOP-like (53.1%), CHOEP/CHOEP-like (63.2%) and brentuximab vedotin/cyclophosphamide/doxorubicin (35.7%), had higher frequency of incident AEs compared to brentuximab vedotin monotherapy (19.2%)... Treatment regimens observed among PTCL patients were consistent with NCCN treatment guidelines, with higher utilization of combination therapies in the 1LOT and higher utilization of monotherapies in subsequent LOTs. Higher frequency of AEs were observed with combination therapies than monotherapy. This study providesevidence that AEs were frequent in all LOTs, suggesting current combination therapies may lack adequate tolerability.
    Retrospective data • Adverse events • HEOR • Real-world evidence • Real-world
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    doxorubicin hydrochloride • cyclophosphamide • Adcetris (brentuximab vedotin) • Istodax (romidepsin)