The activity and safety of the histone deacetylase inhibitor vorinostat (suberoylanilide hydroxamic acid, SAHA) were evaluated in patients with refractory cutaneous T-cell lymphoma (CTCL). Group 1 received vorinostat 400 mg daily, group 2 received vorinostat 300 mg twice daily for 3 days with 4 days rest, and group 3 received vorinostat 300 mg twice daily for 14 days with 7 days rest followed by 200 mg twice daily. Treatment continued until disease progression or intolerable toxicity. The primary objective was to determine the complete and partial response (PR) rate. Time to response (TTR), time to progressive disease (TTP), response duration (DOR), pruritus relief, and safety were determined. Thirty-three patients who had received a median of 5 prior therapies were enrolled. Eight patients achieved a PR, including 7 with advanced disease and 4 with Sézary syndrome. The median TTR, DOR, and TTP for responders were 11.9, 15.1, and 30.2 weeks, respectively. Fourteen of 31 evaluable patients had pruritus relief. The most common drug-related AEs were fatigue, thrombocytopenia, diarrhea, and nausea. The most common grade 3 or 4 drug-related AEs were thrombocytopenia and dehydration. Vorinostat demonstrated activity in heavily pretreated patients with CTCL. The 400 mg daily regimen had the most favorable safety profile and is being further evaluated.

Epigenetic regulation of gene transcription by small-molecule inhibitors of histone deacetylases (HDACs) is a novel cancer therapy. Vorinostat (suberoylanilide hydroxamic acid) is the first FDA-app...

Purpose: Brentuximab vedotin, a monoclonal antibody (cAC10) conjugated to monomethyl auristatin E, targets CD30⁺ receptors. This phase II open-label trial was conducted to evaluate safety and efficacy in CD30⁺ cutaneous T-cell lymphomas. Patients and Methods: Forty-eight patients with CD30⁺ lymphoproliferative disorders or mycosis fungoides (MF) received an infusion of 1.8 mg/kg every 21 days. Results: Forty-eight evaluable patients (22 women and 26 men; median age, 59.5 years) had an overall response rate of 73% (95% CI, 60% to 86%; 35 of 48 patients) and complete response rate of 35% (95% CI, 22% to 49%; 17 of 48 patients). Fifteen (54%; 95% CI, 31% to 59%) of 28 patients with MF responded, independent of CD30 expression. In patients with MF/Sézary syndrome, the overall response rate was 50% (five of 10 patients) in patients with low CD30 expression (< 10%), 58% (seven of 12 patients) in patients with medium expression (10% to 50%), and 50% (three of six patients) in patients with high expression (≥ 50%). Time to response was 12 weeks (range, 3 to 39 weeks), and duration of response was 32 weeks (range, 3 to 93 weeks). All patients with lymphomatoid papulosis (n = 9) and primary cutaneous anaplastic T-cell lymphomas (n = 2) responded; time to response was 3 weeks (range, 3 to 9 weeks), and median duration of response was 26 weeks (range, 6 to 44 weeks). Soluble baseline CD30 levels were lowest in complete responders (P = .036). Grade 1 to 2 peripheral neuropathy was observed in 65% of patients (95% CI, 52% to 79%; 31 of 48 patients), is still ongoing in 55% of patients (95% CI, 41% to 69%; 17 of 31 patients), and resolved in 45% of patients (95% CI, 31% to 59%; 14 of 31 patients), with a median time to resolution of 41.5 weeks. Grade 3 to 4 events were neutropenia (n = 5), nausea (n = 2), chest pain (n = 2), deep vein thrombosis (n = 1), transaminitis (n = 1), and dehydration (n = 1). Dose reductions to 1.2 mg/kg were instituted as a result of grade 2 neuropathy (n = 6), transaminitis (n = 1), and arthralgias and fatigue (n = 2). Conclusion: Brentuximab vedotin is both active and well tolerated in cutaneous T-cell lymphoma and lymphomatoid papulosis, with an overall response rate of 73% and complete response rate of 35%.

Purpose: The purpose of this prospectively collected single center study cohort of 1,263 patients with mycosis fungoides (MF)/Sézary syndrome (SS) is to evaluate the significance of stage and risk of disease progression from initial presentation and to examine other prognostic factors. Patients and Methods: The prognostic variables effecting overall survival (OS) were examined in a unique prospective cohort of 1,263 patients with MF and SS seen by one investigator at MD Anderson Cancer Center (Houston, TX) from 1982 to 2009. Kaplan–Meier estimates were used to determine median OS, progression-free survival (PFS), and disease-specific survival (DSS). Cox proportional hazards regression model assessed prognostic factors. Results: Mean age at diagnosis was 55.33 years. Early mycosis fungoides (stage IA–IIA) represented 71.5% (903 of 1,263) and advanced (stage IIB–IVB) 28.5% (360 of 1,263) patients. Progression to a higher stage occurred in 147 patients (11.6%) of whom 112 (12%) were early and 35 (9.7%) advanced. Death from disease occurred in 102 of 1,263 (8.1%) patients. Median OS was 24.44 years, PFS was 16 years, and median DSS was not reached. OS and PFS were significantly better for early-stage patients with patches (T1a/T2a) than with patches/plaques (T1b/T2b). The PFS analyzed in 1,241 patients found that only 337 (27.2%) had disease progression or had died from disease. Risk factors associated with progression or deaths were advanced age, plaque stage, lactate dehydrogenase (LDH) level, and tumor area. Conclusions: Improved outcome of MF/SS, reflected by OS and PFS for all stages, may result from earlier diagnosis, new therapies, and aggressive treatment of infections. Clin Cancer Res; 18(18); 5051–60. ©2012 AACR.

Key Points: Mogamulizumab was well-tolerated in 41 patients with previously treated mycosis fungoides or Sézary syndrome. Durable responses observed with a global overall response rate of 36.8%; patients with Sézary syndrome had a response rate of 47.1%.