Clinically Significant Responses Achieved with Romidepsin in 37 Patient with Cutaneous T-Cell Lymphoma (CTCL) with Blood Involvement.

Responses to romidepsin, a novel pan-HDAC inhibitor, have been observed in patients (pts) with cutaneous T-cell lymphoma (CTCL) in 2 phase 2 studies. One of these studies, the pivotal study was a phase 2, single-arm, open-label study that enrolled 96 pts with CTCL (Stages IB–IVA) at 33 European and US sites. The objective response rate (ORR) was 34% including 6 complete clinical responses (CCR) in all treated pts. Responses (including CCRs) were seen across all stages of disease with a 42% ORR in stage ≥IIB. The median duration of response (DOR) was 14.9 months (mo). The safety profile was characterized principally by mild (grade 1 and 2) gastrointestinal disturbances, hematologic toxicities, clinical chemistry abnormalities and asthenic conditions [Kim, et al. Blood (ASH Abstracts), Nov 2008; 112: 263]. This report summarizes the analysis of 37 pts in the study with blood involvement (Sézary cells >5% circulating lymphocytes at baseline).

Pts who failed ≥1 prior systemic therapy, had adequate organ function, and ECOG PS 0 or 1 were eligible. Exclusions included significant cardiovascular abnormality or treatment with QTc-prolonging or CYP3A4-inhibiting drugs. Pts received romidepsin 14 mg/m² as a 4-hr IV infusion on days 1, 8, and 15 every 28 days for up to 6 cycles (extended for stable disease [SD] or response). Response was measured with a quantitative composite which included skin involvement [severity-weighted assessment tool (SWAT) or erythroderma scale], lymph node involvement (CT or MRI scans), and blood involvement (circulating Sézary cells assessed by flow cytometry). Pruritus was assessed by visual analog scale (VAS). Pts with baseline VAS ≥30mm were included in pruritus analysis.

Of the 37 pts with >5% circulating Sézary cells, 27 (73%) met the definition of evaluable (received ≥2 cycles of romidepsin) for efficacy. 8 of these 27 pts with blood involvement had a greater blood tumor burden (Sézary cell counts >1000 cells/mm³ and/or Sézary cells >20% of lymphocytes). Mean age was 57±13 yrs and median number of prior systemic therapies was 6 (range 1–14) for all pts. 17 (46%) pts received prior bexarotene and 5 (14%) received prior denileukin diftitox. Response (by composite assessment) and pruritus relief data for the evaluable pts are included in the table. Pts who achieved a response had a rapid, dramatic and durable reduction in Sézary cell counts. ORR was 32% by composite assessment in all pts including 2 CCRs. 5 pts who responded had received bexarotene (including 1 CCR) and 2 had received both denileukin diftitox and bexarotene. The median DOR (for pts with a response by composite assessment) has not been reached; the maximum DOR was 19.8 months. 12 of 27 evaluable pts had erythroderma; 5 of these pts had ≥50% response in skin (4=partial response [PR], 1=SD by composite assessment). 16 of the 37 as-treated pts had erythroderma; 6 of these pts had '50% response in skin (4=PR, 2=SD by composite assessment).

The safety profile in this subset of 37 pts is similar to the overall safety profile of romidepsin in this study and the overall safety profile of romidepsin. No unusual drug-related adverse events were observed.

This study shows clinical benefit associated with romidepsin treatment in a heavily pre-treated group of pts with CTCL with blood involvement. Additional treatment options are needed for these pts. The ORR (32%) in all pts in this group was comparable with the ORR in the entire study (34%). Toxicities associated with romidepsin were tolerable and manageable. The new drug application for the use of romidepsin in CTCL is under review at the FDA.

Robak:F Hoffmann-La Roche: Honoraria. McCulloch:Gloucester Pharmaceuticals: Consultancy. Whittaker:Gloucester Pharmaceuticals: Research Funding.