Complete Responses with Denileukin Diftitox in Cutaneous T-Cell Lymphoma Studies.

Abstract 3745

Poster Board III-681

Cutaneous T-cell lymphoma (CTCL) is a disorder of CD4+ helper T-cells with manifestations in the skin, nodes, and, in advanced stages, blood and visceral sites. For many patients, the clinical course of the disease is chronic and progressive, despite multiple therapeutic interventions. To date, are few controlled clinical trials which demonstrate durable complete responses (CR) in advanced stage patients. Denileukin diftitox (DD) is a recombinant fusion protein targeting interleukin-2 receptor which has demonstrated efficacy in early and advanced stage CTCL with response rates of 30% and 44% in two clinical trials of CTCL pts with Stage Ib-IVA relapsed and refractory CTCL or Stage I-III disease, ≤3 prior therapies respectively. In these trials, patients (pts) were randomized to receive DD at a dose of either 9 or 18 ug/kg/d daily x 5 every 21 days. Another rollover trial enrolled pts who had progressed after prior response with DD (N=29) or were CD25- (N=36); all pts in the rollover trial were treated with DD at 18ug/kg dose. Of 263 intent-to-treat pts in these trials, 227 had CD25+ skin infiltrates by immunohistochemistry (IHC) confirmed by a reference pathologist and 36 were CD25-. Overall, 24 (9.1%) pts attained durable complete response (CR). The median age of the responders was 59, and 12 CR pts were over age 60. Of the CR group, 15 pts had early stage (I-IIa) disease and 9 had advanced stage (IIb-IV) CTCL. The mean prior therapies was 3.6 with 37% of patients having received >3 therapies. Of the 24 CR pts, 21 were CD25+ and 3 were CD25-. Two CR were pts who had previously responded to DD in an earlier clinical trial. Of all pts receiving 9 ug/kg dose (N=80), there were 6 (7.5%) CR; for all pts receiving 18 ug/kg dose (N=183), there were 18 (9.8%) CR. There was no significant difference frequency of CR between the 9 and 18 ug/kg groups (P=0.56) or between the CD25+ (N=118) and CD25- (N=36) pts treated at 18 ug/kg dose (P=0.64). CR rate was similar between the early and advanced stage patients (10.7% vs 8.9% respectively). The median time to response was 53.5 vs 41days for CD25+ pts treated in the 9 and 18 ug/kg groups respectively, and 43 days for the CD25- group. The response durations ranged from 57 days to >1325 days in the CD25+ and 190-400 days in the CD25- groups. Of the 24 CR, 7 have progressed as of the time of the analysis and 17 remain in CR. The overall median PFS at the time of analysis has not been reached (range 169-1388+ days). Of the 24 CR, 3 pts had hypersensitivity reactions and 3 had capillary leak syndrome associated with DD treatment. In summary, these studies demonstrate clinical benefit of DD with CR in both early and advanced CTCL at both 9 and 18 ug/kg doses and with durable responses in a small number of pts whose malignant lymphocytes were CD25- by ICH.