Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: Results of a phase II trial

Duvic, Madeleine; Dummer, Reinhard; Becker, Jürgen C.; Poulalhon, Nicolas; Romero, Pablo Ortiz; Bernengo, Maria Grazia; Lebbe, Célèste; Assaf, Chalid; Squier, Margaret; Williams, Denise; Marshood, Miriam; Tian, Feng; Prince, H. Miles

doi:10.1016/j.ejca.2012.08.017

Cited by 117 publications

(67 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Of 97 patients with baseline pruritus greater than or equal to the baseline interpatient standard deviation, 24 (25%) experienced pruritus relief (definition of relief not provided). [63] The most common panobinostat-related AEs in the phase II study were thrombocytopenia (48%), diarrhea (42%), fatigue (33%), nausea (32%), and decreased appetite (21%). [63] AEs were primarily grade 1/2-only thrombocytopenia (14%, 3%) and neutropenia (9%, 0%) were reported as grade 3 or 4 AEs, respectively.…”

Section: Panobinostatmentioning

confidence: 99%

“…[63] The most common panobinostat-related AEs in the phase II study were thrombocytopenia (48%), diarrhea (42%), fatigue (33%), nausea (32%), and decreased appetite (21%). [63] AEs were primarily grade 1/2-only thrombocytopenia (14%, 3%) and neutropenia (9%, 0%) were reported as grade 3 or 4 AEs, respectively. The most common serious AEs were thrombocytopenia, angina pectoris, congestive cardiac failure, chest pain, and QT prolongation.…”

Section: Panobinostatmentioning

confidence: 99%

“…As a result, an international, open-label, phase II study of oral panobinostat in patients with MF/SS refractory to 2 standard therapies was initiated (N ¼ 139). [63] Oral panobinostat 20 mg/day was given 3 days per week in 28-day cycles, and patients were stratified as bexarotene-exposed (n ¼ 79) or bexarotene-naive (n ¼ 60). Responses were assessed by a combined evaluation of skin (modified severity-weighted assessment tool) or lymph node and visceral (assessed by computed tomography) disease.…”

Section: Panobinostatmentioning

confidence: 99%

See 2 more Smart Citations

Targeting histone deacetylases in T-cell lymphoma

Moskowitz

Horwitz

2016

Leukemia & Lymphoma

View full text Add to dashboard Cite

Section: Panobinostatmentioning

confidence: 99%

Section: Panobinostatmentioning

confidence: 99%

Section: Panobinostatmentioning

confidence: 99%

See 1 more Smart Citation

Targeting histone deacetylases in T-cell lymphoma

Moskowitz

Horwitz

2016

Leukemia & Lymphoma

View full text Add to dashboard Cite

“…Clinically, inhibition of HDAC has shown promise for the treatment of B-cell (3) and T-cell lymphomas (4). The HDAC inhibitors vorinostat, romidepsin, and belinostat are FDAapproved in cutaneous T-cell lymphoma (CTCL), CTCL and peripheral T-cell lymphoma (PTCL), and PTCL, respectively (5,6).…”

Section: Introductionmentioning

confidence: 99%

A Phase I/II Multicenter, Open-Label Study of the Oral Histone Deacetylase Inhibitor Abexinostat in Relapsed/Refractory Lymphoma

Evens

Balasubramanian

Vose

et al. 2016

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Additional targeted therapeutics are needed for the treatment of lymphoma. Abexinostat is an oral pan-histone deacetylase inhibitor (HDACi) displaying potent activity in preclinical models. We conducted a multicenter phase I/II study (N ¼ 55) with single-agent abexinostat in relapsed/refractory lymphoma.Experimental Design: In phase I, 25 heavily pretreated patients with any lymphoma subtype received oral abexinostat ranging from 30 to 60 mg/m 2 twice daily 5 days/week for 3 weeks or 7 days/week given every other week. Phase II evaluated abexinostat at the maximum tolerated dose in 30 patients with relapsed/ refractory follicular lymphoma or mantle cell lymphoma.Results: The recommended phase II dose was 45 mg/m 2 twice daily (90 mg/m 2 total), 7 days/week given every other week. Of the 30 follicular lymphoma and mantle cell lymphoma patients enrolled in phase II, 25 (14 follicular lymphoma, 11 mantle cell lymphoma) were response-evaluable. Tumor size was reduced in 86% of follicular lymphoma patients with an investigatorassessed ORR of 64.3% for evaluable patients [intent-to-treat (ITT) ORR 56.3%]. Median duration of response was not reached, and median progression-free survival (PFS) was 20.5 months (1.2-22.3þ). Of responding follicular lymphoma patients, 89% were on study/drug >8 months. In mantle cell lymphoma, the ORR was 27.3% for evaluable patients (ITT ORR 21.4%), and median PFS was 3.9 months (range, 0.1-11.5). Grade 3-4 treatment-related adverse events (phase II) with !10% incidence were thrombocytopenia (20%), fatigue (16.7%), and neutropenia (13.3%) with rare QTc prolongation and no deaths.Conclusions: The pan-HDACi, abexinostat, was overall well tolerated and had significant clinical activity in follicular lymphoma, including highly durable responses in this multiply relapsed patient population.

show abstract

“…19 Vorinostat, panobinostat, and romidepsin have all been demonstrated to have activity in cutaneous T-cell lymphoma (CTCL) and both vorinostat and romidepsin are now licensed for this disease in a relapsed/refractory setting. [20][21][22] For PTCL, romidepsin has the most mature clinical data. A phase II trial including patients with both CTCL and PTCL showed an overall response rate among 47 PTCL patients of 38% and a median duration of response of 8.9 months.…”

Section: Histone Deacetylase Inhibitorsmentioning

confidence: 99%

New Therapies in T-cell Lymphoma

2014

Lymphoma and Chronic Lymphocytic Leukemias

View full text Add to dashboard Cite

T-cell lymphomas represent 10-12% of all patients with non-Hodgkin lymphoma (NHL) in the Western world. When cutaneous T-cell lymphoma (CTCL) is excluded, peripheral T-cell lymphoma-not otherwise specified (PTCL-NOS), anaplastic large-cell lymphoma (ALCL), and angioimmunoblastic T-cell lymphoma (AITL) represent the overwhelming majority of patients in this population. These diseases remain a great challenge to treat. They are characterized by an aggressive presentation, extranodal disease, paraneoplastic phenomena, and resistance to standard chemotherapeutics. With the rapid development of new molecular gene profiling techniques, it is highly likely that these diseases will be subclassified by molecular abnormalities in the future. An evolving understanding of the tumor molecular pathogenesis will undoubtedly lead to further novel targeted therapies. Immunoconjugates, such as brentuximab vedotin (BV), have provided outstanding responses in relapsed, refractory CD30-positive ALCL. Histone deacetylase (HDAC) inhibitors have shown activity in PTCL and are potentially synergistic with proteasome inhibitors. Denileukin diftitox is an interesting recombinant DNA fusion protein linking fragments of the diphtheria toxin to interleukin-2 (IL-2) that is tested in clinical trials. Crizotinib, a highly specific anaplastic lymphoma kinase (ALK) inhibitor, has shown great promise in small number of patients with ALK-positive ALCL; the future of patients with this disorder looks very promising. Biomarker-driven chemotherapeutics is becoming a critical part of the state-of-the-art treatment in early-and late-phase clinical trials. It is crucial that future trials include sensible biomarker-based designs when future treatments are used in these challenging disorders.KEY WORDS: T cell lymphoma, angioimmunoplastic lymphoma, anaplastic large cell lymphoma, brentuximab, crizotinib disclose no potential conflicts of interest.COPYRIGHT: © the authors, publisher and licensee Libertas academica Limited. this is an open-access article distributed under the terms of the Creative Commons CC-By-nC 3.0 License. CORRESPONDENCE: graham.collins@ouh.nhs.uk this paper was subject to independent, expert peer review by a minimum of two blind peer reviewers. all editorial decisions were made by the independent academic editor. all authors have provided signed confirmation of their compliance with ethical and legal obligations including (but not limited to) use of any copyrighted material, compliance with ICMJE authorship and competing interests disclosure guidelines and, where applicable, compliance with legal and ethical guidelines on human and animal research participants. provenance: the authors were invited to submit this paper.

show abstract

Panobinostat activity in both bexarotene-exposed and -naïve patients with refractory cutaneous T-cell lymphoma: Results of a phase II trial

Cited by 117 publications

References 31 publications

Targeting histone deacetylases in T-cell lymphoma

Targeting histone deacetylases in T-cell lymphoma

A Phase I/II Multicenter, Open-Label Study of the Oral Histone Deacetylase Inhibitor Abexinostat in Relapsed/Refractory Lymphoma

New Therapies in T-cell Lymphoma

Contact Info

Product

Resources

About