Abstract 8546

Pooled analyses of two international, multicenter clinical studies of romidepsin in 167 patients with cutaneous T-cell lymphoma (CTCL)

M. Demierre, S. Whittaker, Y. Kim, et al

Methods: Data from two clinical trials were pooled for more accurate estimates of endpoints and subpopulation investigation. All patients had confirmed cutaneous T-cell lymphoma (CTCL) and all 96 in one study (GPI-04-0001) had received ≥ 1 prior systemic therapy. Patients received romidepsin 14 mg/m2 as a 4-hr infusion on days 1, 8, and 15 every 28 days until disease progression. The primary efficacy endpoint for both studies was overall response rate (ORR) using a composite endpoint that included skin assessment, lymph node and visceral involvement and abnormal circulating T cells/Szary cells.

Results: Among 167 patients (mean age 57) receiving romidepsin (as-treated), 135 patients (81%) received ≥ 2 cycles of treatment and were therefore evaluable for efficacy. Stage ≥ IIB disease was reported in 103 patients (76%). The median number of prior systemic therapies was 2 (range 1–8). The ORR was 41% among evaluable patients and 35% among as-treated patients (see Table):

Evaluable pts* (n = 135)

As-treated pts (n = 167)

ORR, n (%; 95% CI)

55 (41%; 32.4%–49.5%)

58 (35%; 28.1%–43.2%)

CR, n (%)

10 (7%)

10 (6%)

PR, n (%)

45 (33%)

48 (29%)

Median duration of response

14.9 mo

13.8 mo

Median time to disease progression

8.3 mo

6.6 mo

*Received ≥ 2 cycles
CI = confidence interval; CR = complete response; ORR = overall response rate; PR = partial response.

Responses were noted in 42% of patients with stage ≥ IIB disease, in 11 (58%) of 19 patients with Szary syndrome (erythroderma + Szary cells, >1,000/mL or >20% ), in 20 (38%) of 52 patients who received prior bexarotene (Targretin) and 8 (40%) of 20 patients who had received denileukin diftitox (Ontak). The most common drug-related adverse events included nausea (67%), fatigue (49%), anorexia (37%), ECG T-wave changes (29%), anemia (26%), dysgeusia (23%), neutropenia (22%), and leukopenia (20%). Related serious adverse events reported in 2% of patients included supraventicular arrhythmia, ventricular arrhythmia, infection, neutropenia, white blood cell decreases, hyperuricemia, and hypotension. Three deaths were reported as possibly drug-related.

Conclusions: Based on the ORR, CR, durability of response, improvement in all disease compartments, and responses at all stages and in all subpopulations analyzed, romidepsin is a valuable new therapy for patients with CTCL.