romidepsin / Generic mfg. - LARVOL DELTA

Investigation of the classical histone deacetylases and sirtuins using peptide technologies. (PubMed, Cell Chem Biol) - "Due to their central regulatory roles, HDACs have been investigated as drug targets, resulting in several drugs approved for clinical use, including the naturally occurring peptide, romidepsin, spurring the interest in peptide-based inhibitors. In this review, we provide a concise overview of important discoveries enabled by peptide chemistry in the HDAC field and discuss the future potential of high-throughput peptide technologies for HDAC profiling and inhibitor discovery."

Journal • Review

Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study. (PubMed, Lancet Haematol) - P3 | "Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial."

Clinical • IO biomarker • Journal • P3 data • P3 data • Candidiasis • Cardiovascular • Congestive Heart Failure • Follicular Lymphoma • Gastrointestinal Disorder • Heart Failure • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Novel Coronavirus Disease • Oncology • T Cell Non-Hodgkin Lymphoma • BCL6 • CXCL13 • ICOS • MME • PD-1

Novel Use of Tagraxofusp-erzs/Elzonris in CD123-Positive Gamma/Delta Cutaneous T-Cell Lymphoma (SOHO 2026) - "First-line treatment with brentuximab vedotin–based chemotherapy resulted in unclear benefit, and subsequent brentuximab vedotin monotherapy produced only a transient response. Disease progression continued despite additional therapy with romidepsin, which was discontinued due to intolerance...It also highlights the potential role of targeted therapies in refractory PCGDTCL. Further investigation is warranted to determine the clinical significance of CD123 expression and evaluate the efficacy of CD123-directed treatments in this aggressive malignancy."

Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • CD123 • CD5 • CD7 • IL3RA • KEAP1 • TNFRSF8

PDX+Romi: Pralatrexate + Romidepsin in Relapsed/Refractory Lymphoid Malignancies (clinicaltrials.gov) - P1/2 | N=57 | Terminated | Sponsor: Jennifer Amengual | Completed ➔ Terminated; Lack of funding and recruitment complications caused by COVID-19

Trial termination • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Multicenter phase 2 study of romidepsin plus lenalidomide for previously untreated peripheral T-cell lymphoma. (PubMed, Blood Adv) - P2 | "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."

Journal • P2 data • Adult T-Cell Leukemia-Lymphoma • Cardiovascular • Diabetes • Fatigue • Heart Failure • Hematological Malignancies • Hypertension • Infectious Disease • Lymphoma • Neutropenia • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia

Romidepsin-CHOEP followed by high-dose chemotherapy and stem-cell transplantation in untreated Peripheral T-Cell Lymphoma: results of the PTCL13 phase Ib/II study. (PubMed, Leukemia) - "The primary endpoint was not met; therefore, the enrollment was stopped at a planned interim analysis. The addition of romidepsin to CHOEP did not improve the PFS of untreated PTCL patients."

Journal • P1/2 data • Bone Marrow Transplantation • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Transplantation

Combined Oral 5-Azacytidine and Romidepsin are Highly Effective in Patients with PTCL: A Multicenter Phase 2 Study. (PubMed, Blood) - P1/2 | "Combined AZA and ROMI are highly active in PTCL patients and could serve as a platform for novel regimens in this disease. The trial was registered at www.clinicaltrials.gov, #NCT01998035."

Clinical • Journal • P2 data • Hematological Disorders • Hematological Malignancies • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia

Romidepsin Plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Versus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone in Patients With Previously Untreated Peripheral T-Cell Lymphoma: Final Analysis of the Ro-CHOP Trial. (PubMed, J Clin Oncol) - P3 | "Clinical trials frequently include multiple end points that mature at different times. Within the limits of highly heterogeneous second-line treatments, no specific regimen seemed to provide superior disease control. However, a potential benefit was observed with brentuximab vedotin in association with chemotherapy even after excluding anaplastic large-cell lymphoma subtype or after adjusting for histology and international prognostic index in a multivariate model (HR for PFS, 0.431 [95% CI, 0.238 to 0.779]; P = .005)."

Journal • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Research Progress of Histone Deacetylase and Its Inhibitors in Endometriosis. (PubMed, Reprod Sci) - "It also summarizes the therapeutic potential of histone deacetylase inhibitors (HDACis) such as Vorinostat, Romidepsin, and Butyrate demonstrated in preclinical studies, and analyzes the main challenges currently faced in clinical translation. Finally, this article discusses the challenges and future research directions for developing novel endometriosis therapies targeting HDACs, aiming to provide references for in-depth research and clinical translation in this field."

Journal • Review • Endometriosis • Gynecology • Inflammation • Women's Health

ROMIDEPSIN PLUS CHOP VERSUS CHOP IN PATIENTS WITH PREVIOUSLY UNTREATED PERIPHERAL T-CELL LYMPHOMA: FINAL ANALYSIS OF THE RO-CHOP TRIAL (ICML 2023) - P3 | "Five years after randomization of the last patient, outcome of patients treated for PTCL was confirmed to be not significantly different between the Ro-CHOP and CHOP arms, except for PTCL from TFH origin. Second-line treatments led to poor results after disease progression/relapse. The study was sponsored by the LYSARC, with funding provided by Celgene/BMS"

Clinical • Hematological Malignancies • Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Efficacy and Safety of E7777 (improved purity Denileukin diftitox [ONTAK]) in Patients with Relapsed or Refractory Cutaneous T-Cell Lymphoma: Results from Pivotal Study 302 (ASH 2022) - P3 | "Approximately half (34 of 69; 49.3%) of patients had prior exposure to 1 or more FDA-approved targeted therapeutics: romidepsin, brentuximab, or mogamulizumab. In study 302, E7777 at a dose of 9 mcg/kg/day demonstrated clinical efficacy and clinically meaningful benefit in heavily pre-treated patients with relapsed/refractory CTCL. The ORR of 36.2% per IRC (42.3% by investigator assessment) showed that a substantial proportion of these heavily pretreated patients experienced clinical benefit after E7777 treatment similar to ONTAK. The observed tumor responses were rapid, durable, and deep."

Clinical • Cutaneous T-cell Lymphoma • Dermatology • Fatigue • Hematological Malignancies • Hepatology • Infectious Disease • Lymphoma • Oncology • Pruritus • T Cell Non-Hodgkin Lymphoma • IL2

Duvelisib plus romidepsin in relapsed/refractory T cell lymphomas: a phase 1b/2a trial. (PubMed, Nat Med) - P1 | "As reported here, we conducted a phase 1b/2a study of duvelisib in combination with either romidepsin (n = 66) or bortezomib (n = 32) in patients with relapsed/refractory TCL and found that the addition of romidepsin, but not bortezomib, appeared to increase efficacy while attenuating PI3K inhibitor-driven toxicity. These findings support further development of combined PI3K and histone deacetylase (HDAC) inhibition in TCLs and suggest a unique strategy to enable PI3K inhibitor-based combinations for additional patient populations. ClinicalTrials.gov identifier: NCT02783625 ."

Journal • P1/2 data • Fatigue • Hematological Disorders • Hematological Malignancies • Hepatology • Immunology • Lymphoma • Neutropenia • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Functional Precision Medicine Using Ex Vivo Drug Sensitivity Profiling to Guide Therapy Selection in Relapsed/Refractory Multiple Myeloma: Results of a Prospective Clinical Trial (IMS 2026) - P=N/A | "Prior exposure included lenalidomide (100%), bortezomib (97.5%), carfilzomib (85%), daratumumab (82%), pomalidomide (77.5%), and BCMA CAR-T (12.5%). Top-ranked agents by DSS in v1 included bortezomib (median DSS 47.7), carfilzomib (47.3), panobinostat (47.0), and romidepsin (45.4). In v2, leading agents were marizomib ( 46.1), carfilzomib (40.2), ixazomib (37.2), and oprozomib (31.6)...ROC analysis for bortezomib (n=12) and selinexor (n=8) yielded AUCs of 0.471 and 0.462, respectively... High-throughput drug sensitivity testing was feasible in heavily pretreated RRMM and generated actionable results in nearly all patients. DSS-based prediction varied across agents, highlighting the need for drug-specific thresholds and larger validation cohorts. These findings support further development of functional precision medicine as a complementary tool to refine therapeutic decision-making in RRMM"

Late-breaking abstract • Preclinical • Hematological Malignancies • Leukemia • Multiple Myeloma • Plasma Cell Leukemia • Plasmacytoma • SDC1

Oral Azacytidine in Patients with Relapsed/Refractory Angioimmunoblastic T-Cell Lymphoma: Final Analysis of the Oracle Phase III Study (ASH 2022) - P3 | "Patients & Eighty-six patients with relapsed/refractory AITL or nodal follicular helper T-cell lymphoma were randomized between CC-486 (n=42) and investigator's choice (gemcitabine, n=24, bendamustine n=16, romidepsin n=4) between November 2018 and February 2021. The trial did not meet its primary endpoint, most likely due to an optimistic hypothesis of PFS improvement, resulting in a study including 86 patients which could be underpowered to detect a clinically meaningful difference. 5-azacytidine had a favourable safety profile compared to standard of care and was associated with prolonged overall survival, suggesting that this drug might have a role in the treatment of TFH PTCL and could be investigated in combination with other agents."

Clinical • P3 data • Follicular Lymphoma • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Thrombocytopenia • DNMT3A • IDH2 • RHOA • TET2

Cognitive and synaptic impairment induced by deficiency of autism risk gene Smarcc2 and its rescue by histone deacetylase inhibition. (PubMed, Mol Psychiatry) - "Treatment of Smarcc2-deficient mice with romidepsin, a class I HDAC inhibitor, normalized histone acetylation, working memory, synaptic genes and currents. These findings highlight the critical role of Smarcc2 in regulating cognitive and synaptic function, suggesting that targeting HDAC could alleviate deficits in Smarcc2-associated neurodevelopmental disorders."

Journal • Autism Spectrum Disorder • CNS Disorders • Developmental Disorders • Genetic Disorders • Mood Disorders • Psychiatry • HDAC2

Epigenetic inhibition of HDAC2 by a novel inhibitor JRM-28 enhances neuroplasticity and modulates amyloid pathology in Alzheimer's disease models | Poster Board #1364 (ACS-Fall 2026) - "Guided by the pharmacophore of the FDA-approved pan-HDAC inhibitor romidepsin, we designed and synthesized MJM-1 and subsequently developed JRM-28, an HDAC2 inhibitor...Collectively, these findings demonstrate that HDAC2 inhibition by JRM-28 modulates neuroplasticity-associated signaling pathways and supports cognitive function in vivo. Ongoing studies are focused on extending these findings to Alzheimer's disease mouse models to further define therapeutic potential."

Alzheimer's Disease • CNS Disorders • HDAC2 • MME

Integrated Patient-Derived Xenograft and Patient-Derived Cell Models Reveal Therapeutic Vulnerabilities Beyond Standard-of-Care Therapy in Endometrial Cancer. (PubMed, bioRxiv) - "Importantly, a low-dose combination of the DNA methyltransferase inhibitor 5-azacytidine and the histone deacetylase inhibitor romidepsin significantly suppressed tumor growth across six independent PDX models. Together, these findings establish a comprehensive PDX and PDC platform as a robust translational resource. By capturing the histopathologic and molecular diversity of EC and identifying clinically actionable therapeutic advantages, including an epigenetic combination regimen, this study offers a translational resource for preclinical drug evaluation."

Journal • Endometrial Cancer • Gynecologic Cancers • Oncology • Solid Tumor

FK228-Mediated Restoration of Tight Junction Proteins in Diabetic Neuropathy. (PubMed, Biology (Basel)) - "FK228 treatment demonstrated changes in cold pain sensitivity as well as the expression of tight junction proteins and stress related markers in both in vivo and in vitro models of diabetic neuropathy. These findings indicate that HDAC inhibition by FK228 may support the maintenance of tight junction protein expression and alter cellular stress responses in the spinal cord and DRG, suggesting a possible role of FK228 in mitigating DPN."

Journal • Diabetes • Diabetic Neuropathy • Immunology • Inflammation • Metabolic Disorders • Pain • Type 2 Diabetes Mellitus • CLDN1 • EGFR • HDAC2 • OCLN • TJP1

From design to clinic: Medicinal chemistry and pharmacology of approved epigenetic drugs. (PubMed, Eur J Med Chem) - "This review explores the ten epigenetic drugs that have attained worldwide regulatory approval for human therapy: the DNA methyltransferase inhibitors azacitidine (2004) and decitabine (2006), the histone deacetylase inhibitors vorinostat (2006), romidepsin (2009), belinostat (2014), panobinostat (2015) tucidinostat (2015) and givinostat (2024), and the histone methyltransferase inhibitors tazemetostat (2020) and valemetostat (2022). The history and strategy of their discovery and development, their biological targets and mechanisms of action and their therapeutic use. In addition, current advancements and efforts, as well as future perspectives in the design and clinical approval of new epigenetic drugs are discussed."

Journal • Review • Oncology

Study Investigating Intravesical HDAC Inhibition to Improve Response to Immuno-Oncology Agents (clinicaltrials.gov) - P1 | N=12 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Suspended ➔ Recruiting

Enrollment open • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Malignant T Cells Operate at the Edge of Redox Tolerance and Propagate Oxidative Stress in Cutaneous T-Cell Lymphoma. (PubMed, J Invest Dermatol) - "Romidepsin-induced apoptosis is similarly NAC-dependent...This effect is amplified by S. aureus activation. Taken together, we find that CTCL harbors a rare SOD2-high/PRDX2-low redox imbalance and that malignant T-cells are sensitive to ROS induction while able to propagate oxidative stress to keratinocytes."

Journal • Atopic Dermatitis • Cutaneous T-cell Lymphoma • Dermatitis • Dermatology • Hematological Malignancies • Immunology • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma • PRDX2 • SOD2

Beyond Romidepsin: Novel Therapeutic Targets and Emerging Strategies for Relapsed and Refractory Peripheral T-Cell Lymphoma. (PubMed, Clin Lymphoma Myeloma Leuk) - "Following romidepsin's withdrawal from the R/R PTCL indication in 2021, the only FDA-approved agents are belinostat and pralatrexate, and Brentuximab Vedotin...EZH2 inhibitors represent a mechanistically novel class: valemetostat produced an ORR of 43.7% with a median duration of response of 11.9 months. JAK/STAT inhibitors, including golidocitinib (ORR 44.3%) and cerdulatinib (ORR 51.9% in AITL/TFH), show subtype-selective activity. Rational combinations yield superior efficacy: duvelisib plus romidepsin achieved ORR of 56% (CR 44%), while azacitidine combined with romidepsin produced ORR of 61% (CR 48%), particularly in TFH-phenotype disease (ORR 80%)...The Ro-CHOP trial's failure in unselected populations, contrasted with efficacy signals in nTFHL subsets, underscores a critical lesson: PTCL is not one disease, and future trial designs must incorporate biomarker-driven enrichment strategies to advance precision therapeutics. Improved outcomes can be expected..."

Journal • Review • Gene Therapies • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • DNMT3A • KLRD1 • RHOA • TET2

Effects of the HDAC6/8 Inhibitor MC1568, Alone and in Combination With Fluconazole, in Non-Albicans Candida Species Infections. (PubMed, Microbiologyopen) - "This study evaluated the antifungal efficacy of three clinically approved histone deacetylase inhibitors (HDACi)-Vorinostat, Romidepsin, and Tucidinostat-along with the HDAC6/8-selective inhibitor MC1568, alone and in combination with Fluconazole. When tested in human retinal pigment epithelium (RPE) cells, three different MC1568/Fluconazole combinations displayed low toxicity. These findings highlight the potential of the HDAC6/8 inhibitor MC1568 as adjunct therapy to combat NAC infections, warranting further research to optimize antifungal efficacy while minimizing toxicity."

Journal • Infectious Disease

A MULTICENTER, OPEN-LABEL, PHASE 3, RANDOMIZED TRIAL OF DUVELISIB VS INVESTIGATOR'S CHOICE (GEMCITABINE OR BENDAMUSTINE) IN RELAPSED/REFRACTORY NODAL T-CELL LYMPHOMA WITH T-FOLLICULAR HELPER PHENOTYPE (EHA 2026) - P2, P3 | "Currently, the only agent approved in the EU/UK for treatment of R/R PTCL is brentuximab vedotin for anaplastic large-cell lymphoma. Novel agents such as romidepsin, belinostat, and pralatrexate have received accelerated approvals outside the EU/UK, but to date, none have received full approval...TERZO will test the hypothesis that DUV monotherapy is associated with improved outcomes versus GEM or BEN in patients with R/R nTFHL. TERZO is the only phase 3 study dedicated to nTFHL in the EU/UK, designed to address this serious unmet need."

Clinical • P3 data • Chronic Lymphocytic Leukemia • Follicular Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • Small Lymphocytic Lymphoma • T Cell Non-Hodgkin Lymphoma

Neuroprotective in vitro effects of histone deacetylase 6-selective inhibitor SW-100 toward oxaliplatin-derived toxicity. (PubMed, Mol Pharmacol) - "In this study, we tested the antitumorigenic abilities of 3 different HDACis (SAHA, romidepsin, and SW-100) in combination with oxaliplatin (OHP) in 3 colorectal cancer cell lines (HT-29, HCT-15, and Caco-2)...SIGNIFICANCE STATEMENT: Chemotherapy-induced peripheral neuropathy is a common side effect of oxaliplatin, a drug used for the treatment of colorectal cancer. This study demonstrated that in vitro cotreatment with the histone deacetylase 6 selective inhibitor, SW-100, attenuates the neurotoxic effect of oxaliplatin while maintaining the efficacy of the treatment."

Journal • Preclinical • Colorectal Cancer • Hematological Disorders • Hematological Malignancies • Oncology • Pain • Solid Tumor • CASP3