Duration of response in three phase III studies of denileukin diftitox in cutaneous T-cell lymphoma (CTCL).

Abstract

8055 Background: Although responses to systemic chemotherapy or electron beam radiation in CTCL patients can be relatively high, the duration of response (DOR) can be disappointingly short since patients may relapse, develop resistance, or become refractory to therapy. Outcome for patients with CTCL worsens with higher disease stage and number of prior therapies. We looked at DOR to denileukin diftitox (DD), a fusion protein targeting the IL-2 receptor in malignant T cells. Methods: DOR in pooled intent-to-treat populations of patients with recurrent/persistent CTCL was calculated from three phase III trials of DD in patients with stage Ia-III disease. DD patients were categorized as 1) patients naive to DD (n= 198), 2) patients retreated with DD (n= 29), and 3) CD25 negative patients (n=36). In all three trials, DD was administered as courses of 9 or 18 μ g/kg IV daily for 5 days, repeated every 21 days, up to 8 courses. DOR was defined as date of first evidence of documented response until date of relapse, the initiation of new anticancer treatment, or the last observation on study. Results: The current analysis included 263 DD-treated patients and 44 placebo (PBO) patients. The median DOR in patients receiving DD was approximately 3 times higher than DOR for patients receiving placebo (277 days vs. 81 days, <0.0001). Incidence of drug-related immunosuppression, cumulative toxicity, or myelotoxicity was minimal. Overall response rates were 16% for placebo, 31% for 9 μ g/kg DD, 41% for 18 μ g/kg DD, 28% for retreated, and 31% for CD25 negative patients. Conclusions: DD appears to improve DOR in patients with CTCL. The estimated median duration of the response in all DD arms was more than triple that of patients receiving placebo. Placebo(N=44) All DDtreated(N=263) CD25+ CD25− 9 μ gDD naive(N=80) 18 μ gDD naive(N=118) 18 μ gretreated(N=29) 18 μ gDD naive(N=36) All 18 μ gtreated(N=183) No. of patients 7 100 25 56 8 11 75 Baseline stage ≤IIa 3 68 18 37 6 7 50 Baseline stage ≥IIb 4 32 7 19 2 4 25 Median DOR (Days) 81 277 277 267 274 340 274 95% CI for median (52, 92) (220, 820) (127, —) (197, —) (131, —) (141, — ) (203, —) Min, max 43, 127 42, 1325 42, 1325 43, 1247 75, 321 58, 400 43, 1247 P value (vs. PBO) – < 0.0001 0.0297 < 0.0001 0.0082 0.0036 < 0.0001 Author Disclosure Employment or Leadership Position Consultant or Advisory Role Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Eisai, Ligand Eisai