Romidepsin: A Histone Deacetylase Inhibitor for Refractory Cutaneous T-Cell Lymphoma

Romidepsin: A Histone Deacetylase Inhibitor for Refractory Cutaneous T-Cell Lymphoma (October).

Kim M, Thompson LA, Wenger SD, O'Bryant CL.

Source

< Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Aurora.

Abstract

OBJECTIVE:

To evaluate the efficacy and safety of romidepsin in refractory cutaneous T-cell lymphoma (CTCL).

DATA SOURCES:

An English-language literature search of PubMed and MEDLINE (Nov 2011-April 2012) was performed using the terms romidepsin, CTCL, and depsipeptide (FK228). The National Comprehensive Cancer Network guidelines, American Society of Clinical Oncology abstracts, American Society of Hematology abstracts, clinical trial registry, and prescribing information from the manufacturer were reviewed for additional information.

STUDY SELECTION AND DATA EXTRACTION:

Phase 1 and 2 trials evaluating the efficacy and safety of romidepsin were reviewed with a specific focus on its use in cutaneous T-cell lymphoma. All peer-reviewed articles with clinically relevant information were evaluated for inclusion.

DATA SYNTHESIS:

In advanced stage CTCL, single or combination chemotherapy regimen responses are variable and lack durability. Romidepsin is a histone deacetylase inhibitor approved for refractory cutaneous T-cell lymphoma. Romidepsin has shown an improvement in duration of response and pruritus over traditional therapy. In 2 independent Phase 2 trials, romidepsin showed an overall response rate of 34% and durable response of 13-15 months in patients with refractory CTCL. The most frequent toxicities of romidepsin include nausea, vomiting, fatigue, or myelosuppression. Clinically insignificant QT interval changes have been observed but did not correlate with a decrease in left ventricular ejection fraction, or elevated laboratory markers of myocardial damage.

CONCLUSIONS:

Romidepsin is an effective, durable, and well-tolerated single-agent therapy in patients with refractory CTCL and should be considered for formulary addition in this population.

Annals of Pharmacotherapy

Long-term follow-up and survival of cutaneous T-cell lymphoma patients treated with extracorporeal photopheresis.

Oct 2012

Knobler R, Duvic M, Querfeld C, Straus D, Horwitz S, Zain J, Foss F, Kuzel T, Campbell K, Geskin L.

Source

Department of Dermatology, Medical University of Vienna, Vienna, Austria.

Abstract

PURPOSE:

Extracorporeal photopheresis (ECP) is effective for treating cutaneous T-cell lymphoma. In 1987, a pivotal trial showed 81% overall response rate (ORR) using outdated criteria. No long-term follow-up was available for assessing survival. This study applies modern criteria to the 1987 trial to assess the impact of ECP on skin responses and also updates overall survival of the cohort.

METHODS:

Generalized erythroderma (GE, stage T4, n = 31) or extensive patch-plaque (EPP, stage T2, n = 8) patients received ECP (mean 3.9 years' duration). Patients achieving ≥ 50% partial skin response, ≥ 90% near-complete skin response, treatments required, and duration of response (DOR) were determined. Overall survival (OS) from diagnosis and first ECP treatment was determined for all patients and the GE cohort.

RESULTS:

Patients showed 74% skin ORR using modern criteria; 33% of patients achieved ≥ 50% partial skin response (after median 7.1 months, mean 23 ECP treatments); 41% achieved ≥ 90% improvement (after median 19.6 months, mean 40 ECP treatments). Mean DOR was 14 months for ≥ 50% improvement and 8.9 months for ≥ 90% improvement. Response rates were comparable for GE and EPP cohorts. Median OS was 9.2 years from diagnosis and 6.6 years from ECP initiation (71.6 months follow-up).

CONCLUSION:

Analysis of long-term follow-up confirmed durable responses and prolonged survival of patients treated with ECP.

Wiley OnLine