Istodax (romidepsin) / Astellas, BMS - LARVOL DELTA

Ford JG, Koh MJ, Lenart AW, et al. Real-world evidence of duvelisib and romidepsin in relapsed/refractory peripheral and cutaneous T-cell lymphomas. Blood Adv. 2025;9(16):4286-4305. (PubMed, Blood Adv) - No abstract available

HEOR • Journal • Real-world evidence • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

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

Rationalising the inclusion of HDAC inhibitors with standard-of-care chemotherapy for high-risk neuroblastoma (LCC 2026) - "Within treatment naïve neuroblastomas, priming with the histone deacetylase (HDAC) inhibitor Vorinostat could overcome this chemoresistance and sensitise tumours to treatment with specific standard-of-care chemotherapies...A key observation from this study was that the HDAC inhibitors Romidepsin and Panobinostat led to increased apoptosis...These mechanistic insights are now being leveraged to design rationalised treatment regimens that combine these HDAC inhibitors with standard-of-care chemotherapies. This includes the addition of a priming step with Belinostat, which we have now demonstrated is capable of significantly reducing tumour growth and doubling median survival times in patient-derived xenograft models treated with topotecan and cyclophosphamide."

Neuroblastoma • Solid Tumor

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

A real-world retrospective study of romidepsin: Insights from the Food and Drug Administration Adverse Event Reporting System. (PubMed, Medicine (Baltimore)) - "These findings contribute to the ongoing evaluation of the safety profile of romidepsin and can inform clinical monitoring and risk assessment. The newly identified adverse events warrant further investigation to elucidate their underlying mechanisms."

Adverse events • Journal • Real-world evidence • Retrospective data • Hematological Disorders • Neutropenia • 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

Romidepsin, CC-486 (5-azacitidine), Dexamethasone, and Lenalidomide (RAdR) for Relapsed/Refractory T-cell Malignancies (clinicaltrials.gov) - P1 | N=26 | Completed | Sponsor: National Cancer Institute (NCI) | Active, not recruiting ➔ Completed | Trial completion date: May 2026 ➔ Dec 2025

Trial completion • Trial completion date • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Peripheral T-cell Lymphoma • Sezary Syndrome • T Cell Non-Hodgkin Lymphoma

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

SYNACTHIV: Evaluation of the Safety and the Tolerability of a Combination of Two HIV Inducers in Patients With Undetectable Viral Load (clinicaltrials.gov) - P1 | N=9 | Completed | Sponsor: ANRS, Emerging Infectious Diseases | Recruiting ➔ Completed | N=15 ➔ 9 | Trial completion date: Apr 2026 ➔ Dec 2025 | Trial primary completion date: Apr 2026 ➔ Dec 2025

Enrollment change • Trial completion • Trial completion date • Trial primary completion date • Human Immunodeficiency Virus • Infectious Disease • CD4

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 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

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

EPI-SauriCas9-based mouse ovarian cancer models recapitulating pten deletion in patients. (PubMed, Commun Biol) - "High-throughput drug screening identifies FK228 and thioguanine as promising therapeutic candidates, both of which show in vivo efficacy and are validated in PTEN-deleted organoids. Together, these results establish MEPP as a platform for studying PTEN-deleted ovarian cancer and provide a strategy for generating clinically relevant tumor models through targeted gene editing."

Journal • Preclinical • Gynecologic Cancers • Oncology • Ovarian Cancer • Solid Tumor • PTEN • TP53

In Vitro and In Vivo Efficacy of Romidepsin Alone and in Addition to Standard of Care for Treatment of Ewing Sarcoma. (PubMed, Cancers (Basel)) - "In vitro we identified that romidepsin synergizes with doxorubicin and etoposide and that it increases the efficacy of the standard of care combinations VDC/IE. In vivo, the combination of romidepsin and ifosfamide/etoposide (IE) leads to a significant decrease in tumor volume compared to that of IE alone. Our data indicates that romidepsin improves efficacy of chemotherapeutic agents in vitro and leads to a decreased tumor volume in vivo, suggesting that the addition of romidepsin may improve upfront treatment in ES patients."

Journal • Preclinical • Ewing Sarcoma • Oncology • Pediatrics • Sarcoma • Solid Tumor • CASP3 • CASP7

In Vitro and In Vivo Efficacy of Romidepsin Alone and in Addition to Standard of Care for Treatment of Ewing Sarcoma (Multidisciplinary Digital Publishing Institute) - "In vitro we identified that romidepsin synergizes with doxorubicin and etoposide and that it increases the efficacy of the standard of care combinations VDC/IE. Further, the combination treatments lead to an increase in caspase 3/7 cleavage, a decrease in DNA damage repair proteins, and an accumulation of DNA damage."

Preclinical • Ewing Sarcoma

A functional precision medicine clinical trial in Relapsed/Refractory multiple myeloma: Prospective study of a high throughput drug sensitivity assay on correlation of drug sensitivity scores with treatment response (ASH 2025) - P=N/A | "All patients (100%) had prior exposure to lenalidomide, 97.5% to bortezomib, 85% to carfilzomib, 82% to daratumumab, 77.5% to pomalidomide, and 12.5% BCMA CAR-T therapy...From Oncopanel2 v1, the top drugs by DSS included bortezomib (median DSS 47.7), carfilzomib (median DSS 47.3), panobinostat (median DSS 47), and romidepsin (median DSS 45.4). From Oncopanel2 v2, the top drugs by DSS were marizomib (an investigational PI, with median DSS 46.1), carfilzomib (median DSS 40.2), ixazomib (median DSS 37.2), and oprozomib (an investigational PI, with median DSS 31.6)... The use of a high throughput drug sensitivity assay was feasible among patients with relapsed/refractory MM. In our analysis of drug-specific DSS thresholds for bortezomib and Selinexor, DSS performance varied by agent, highlighting the need for drug-specific threshold optimization. In the patients who received Selinexor, there was a non-significant tendency toward higher DSS scores in responders,..."

Clinical • IO biomarker • Hematological Malignancies • Leukemia • Multiple Myeloma • Plasma Cell Leukemia • Plasmacytoma • SDC1

A tale of two lymphomas: A rare case of transformative post-transplant lymphoproliferative disorder (ASH 2025) - "Our 61-year-old patient underwent a living-unrelated renal transplant in 2014 for focal segmental glomerulosclerosis and was maintained on mycophenolate mofetil (MMF) and cyclosporine (CsA)...MMF was discontinued, and he received four weekly doses of rituximab (375 mg/m²), achieving complete remission (CR) and was consolidated with four additional Rituximab doses by Jan 2024...After improvement of liver and kidney function, therapy was escalated to brentuximab vedotin (BV) with cyclophosphamide, doxorubicin, and prednisone (CHP), given his CD30 expression...After detailed goals-of-care discussions, he and the care team elected to proceed with additional therapy with EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin), since he already received azacitidine, romidepsin, and BV-CHP...His care underscores the importance of multidisciplinary collaboration, patient-centered decision-making, and longitudinal follow-up. He has been referred to our..."

Clinical • IO biomarker • Post-transplantation • Bone Marrow Transplantation • Chronic Kidney Disease • Epstein-Barr Virus Infections • Febrile Neutropenia • Focal Segmental Glomerulosclerosis • Follicular Lymphoma • Glomerulonephritis • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Hepatology • Immunology • Infectious Disease • Liver Failure • Lymphoma • Nephrology • Peripheral T-cell Lymphoma • Rare Diseases • T Cell Non-Hodgkin Lymphoma • Transplantation • BCL6 • CD21 • CD4 • CD5 • CD7 • ICOS • JAK1 • PD-1 • RHOA • TET2 • TNFRSF8

Survival and response rates of histone deacetylase inhibitors in peripheral T-cell lymphoma: A comprehensive systematic review and meta-analysis of 67 studies. (ASH 2025) - "It has high relapses and unfavorable prognoses with first-line chemotherapy regimens (cyclophosphamide, doxorubicin, vincristine, and prednisone)...Currently, romidepsin, vorinostat, and belinostat have US FDA approval for the treatment of relapsed/refractory PTCL, while chidamide is approved in China but is not approved in the US...HDACi monotherapy in patients with R/R T cell lymphoma, demonstrated an ORR, with chidamide [42%; 95% CI: (0.148, 0.57), p-value = <0.00001, I2=85%] followed by romidepsin [30%; 95% CI: (0.25, 0.35), p-value = <0.00001, I2=35%], abexinostat [28%; 95% CI: (0.19, 0.37), p-value = <0.00001], belinostat [26%; 95% CI: (0.19, 0.33), p-value = <0.00001, I2=0%]... This meta-analysis demonstrates that HDACi has shown overall improved response rates and survival in PTCL patients. However, chidamide has higher response rates than romidepsin in previously treated (UT) patients. In R/R patients, complete remission is higher with romidepsin;..."

Epigenetic controller • Retrospective data • Review • Adult T-Cell Leukemia-Lymphoma • Extranodal Natural Killer/T-cell Lymphoma • Hematological Malignancies • Lymphoma • Natural Killer/T-cell Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK

Rare cancer, rare survivors: A 20-year single-center review of adult T-cell lymphoma/leukemia treatment outcomes (ASH 2025) - "Among acute ATLL pts (n=25), initial therapy included CHOP or CHOEP (40%), hyperCVAD (28%), and Zidovudine + interferon a (AZT+IFN) (20%)...Among lymphomatous subtypes pts (n=24), the majority received CHOP-based regimens initially (79%), followed by salvage with ICE, pralatrexate, or romidepsin...A small number of long-term survivors were observed in acute ATLL with limited tumor burden in the lymph node involvement, associated with early use of AZT+IFN, followed by mogamulizumab, or AlloHCT...Unfortunately, we currently lack highly effective frontline treatment options, which makes consolidative strategies such as transplantation difficult to execute. These findings underscore the urgent need for earlier recognition, subtype-adapted therapy, and suggest the incorporation of antiviral and immune-based strategies to improve ATLL outcomes."

Clinical • Review • Adult T-Cell Leukemia-Lymphoma • Bone Marrow Transplantation • Cutaneous T-cell Lymphoma • Endocrine Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Metabolic Disorders • Non-Hodgkin’s Lymphoma • Oncology • T Cell Non-Hodgkin Lymphoma

Continued risk of relapse in peripheral T-cell lymphoma even in patients who achieved complete response after initial therapy (ASH 2025) - "Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) has been the standard initial therapy for PTCL; however, clinical outcomes remain suboptimal. The introduction of brentuximab vedotin (BV)-CHP has improved survival in CD30-positive PTCL patients (pts) and has become the standard therapy for this subgroup...Of the 33 pts who subsequently received salvage therapy, 22 received at least one novel agent (e.g., BV, romidepsin, pralatrexate, tucidinostat), and 19 received conventional chemotherapy... PTCL pts who achieved CR after initial therapy demonstrated favorable long-term survival. However, more than half experienced relapse, with no clear plateau in relapse risk. This finding indicates a continued risk of relapse and highlights the need for long-term monitoring."

Clinical • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma • ALK • TNFRSF8

NF-κB is a potential therapeutic target for histone deacetylase inhibitor-resistant cutaneous T-cell lymphoma (ASH 2025) - "Histone deacetylase (HDAC) inhibitors, including vorinostat and romidepsin, are used clinically to restore the expression of tumor suppressor genes known to be epigenetically suppressed in CTCL...Finally, we confirmed that HDAC inhibitor-resistant cell lines displayed heightened sensitivity to inhibition of the NF-κB pathway by bortezomib, a proteasome inhibitor that prevents IκB degradation and thereby blocks NF-κB activation, and dimethyl fumarate, an immunomodulatory and anti-inflammatory drug that suppresses NF-κB signaling by reducing the nuclear translocation and phosphorylation of p65. Conclusion : These findings suggest that aberrant NF-κB activation is a central driver of HDAC inhibitor resistance in CTCL. Our results provide a strong rationale for exploring NF-κB inhibition as a therapeutic strategy to restore or enhance the efficacy of HDAC-inhibitor-based therapies, overcome HDAC inhibitor resistance, and improve the outcomes of patients with CTCL."

Epigenetic controller • Cutaneous T-cell Lymphoma • Hematological Malignancies • Lymphoma • T Cell Non-Hodgkin Lymphoma • Targeted Protein Degradation • BCL3 • EGR1 • EP300 • GATA3 • HDAC1 • HDAC2 • HDAC3 • HIC1 • RELA • SOX2 • STAT3

The NLP protein is a novel regulator of G2-m Phase of the cell cycle critical for proliferation of human peripheral T-cell lymphomas (ASH 2025) - "Standard regimens such as CHOP or R‑CHOP, along with approved targeted agents(belinostat, romidepsin, pralatrexate), have yielded limited long‑term benefit, with 5‑year survival rates ofonly 20–30%...Homozygous NLP knockout mice are viable butshow ~10% reduction in the body size suggesting that mouse NLP is important but not essential fornormal development.Altogether, our findings identify NLP as a novel regulator of the G2–M phase of the cell cycle with acritical role in the proliferation of malignant T-cells. Given its predicted druggable structure, NLPrepresents a promising candidate for the development of novel targeted PTCL therapies."

Hematological Malignancies • Liver Cancer • Lymphoma • Non-Hodgkin’s Lymphoma • Peripheral T-cell Lymphoma • Renal Cell Carcinoma • Solid Tumor • T Cell Non-Hodgkin Lymphoma • ATF5 • BRCA1 • CHEK2 • EPAS1 • RPL10

BTK regulates EZH2 stability in myeloid leukemia associated with down syndrome (ASH 2025) - "Although most ML-DS patients respond favorably to chemotherapy, outcomes remainpoor in relapsed or refractory cases, which highlights the need for novel therapeutic strategies.We previously demonstrated that dual inhibition of EZH2 and class I histone deacetylases (HDAC) byusing GSK126 and romidepsin synergistically suppressed ML-DS cell viability (Cicek et al., 2022)...Notably, BTK inhibition by Pirtobrutinib, a FDA-approved reversible BTK inhibitor,recapitulated the effects of combination treatment by reducing EZH2 protein level and inducing celldeath of relapsed ML-DS PDX cells via apoptosis. Proteosome inhibition with MG132 in the presence ofPirtobrutinib rescued EZH2 level, indicating that BTK inhibition reduces EZH2 stability via the ubiquitin-proteasome pathway. Furthermore, BTK inhibition suppressed key E2F-related oncogenic targets,including c-MYC, Bcl-xL and MCL-1, while upregulating the cell cycle inhibitor p21.Together, these findings highlight BTK as a novel..."

Acute Myelogenous Leukemia • Developmental Disorders • Genetic Disorders • Hematological Malignancies • Leukemia • Targeted Protein Degradation • ANXA5 • BCL2L1 • CASP3 • CASP7 • CD34 • GATA1 • MYC • RAD21 • STAG2 • SUZ12