User login
The recombinant fusion protein denileukin diftitox (DD) produced a significant and durable overall response rate at 2 dose levels as compared to placebo in patients with cutaneous T-cell lymphoma (CTCL).
These phase 3 results confirm the efficacy, safety, and clinical benefit of DD in CD25-positive, stage IA to III CTCL. An earlier trial included more heavily pretreated late-stage patients.
Andres Negro-Vilar, MD, PhD, and colleagues reported the current results March 8 ahead of print in the Journal of Clinical Oncology.
The investigators randomized 144 patients—44 to placebo, 45 to 9 mg/kg/day DD, and 55 to 18 m/kg/day DD. Patients received the treatment on days 1 through 5 of each 21-day course for up to 8 courses.
Patients were a median age of 59 years, two thirds had disease stage IIA or earlier, and 94% had received 3 or fewer prior therapies. Prior therapies included phototherapy (48%), interferon alfa (20%), electron beam readiotherapy (48%), system cytotoxic chemotherapy (26%), topical chemotherapy (25%), and other therapies (30%).
Most patients (85%) had mycosis fungoides, 6.3% had Sézary syndrome, and 8.3% had other cutaneous lymphomas.
After a median of 6 treatment courses, patients receiving either dose of DD had a statistically significant overall response rate (ORR) compared to placebo.
Patients in the 18 µg DD group had a 49% ORR, including 9% complete response (CR) or clinical complete response (CCR). This compared to an ORR of 16% for placebo patients (P=0.0015).
Patients in the 9 µg group had a 37.8% ORR, including 11% CR/CCR. This ORR was also significantly better compared to placebo (P=0.0297).
About half of the placebo patients experienced progressive disease compared with 21% of the DD-treated patients.
Progression-free survival (PFS) was significantly longer in the DD-treated patients. The 18 µg-arm had a median PFS of 971 days, the 9 µg-arm had a median PFS of 794 days, and the placebo patients had a median PFS of 124 days.
DD-treated patients in both dose groups experienced significantly superior duration of response, time to response, and time to treatment failure compared to the placebo patients.
DD-treated patients reported more adverse events and serious adverse events than the placebo patients. The investigators observed that the AEs occurred most frequently during the first 2 or 3 treatment courses and then declined to placebo levels.
DD combines the diphtheria toxin with human interleukin-2 (IL-2). DD binds to and is internalized by the IL-2 receptor. Therefore, it is most efficient at killing cells that express the intermediate- or high-affinity IL-2 receptor.
The investigators suggest that the 18 µg/kg/day dose may improve the response rate without increasing toxicity. The higher dose “provides more benefit, such as a higher ORR and statistically significant improvements in several supportive end points . . . DD may represent an important treatment option for many patients with these challenging diseases,” they said. 
The recombinant fusion protein denileukin diftitox (DD) produced a significant and durable overall response rate at 2 dose levels as compared to placebo in patients with cutaneous T-cell lymphoma (CTCL).
These phase 3 results confirm the efficacy, safety, and clinical benefit of DD in CD25-positive, stage IA to III CTCL. An earlier trial included more heavily pretreated late-stage patients.
Andres Negro-Vilar, MD, PhD, and colleagues reported the current results March 8 ahead of print in the Journal of Clinical Oncology.
The investigators randomized 144 patients—44 to placebo, 45 to 9 mg/kg/day DD, and 55 to 18 m/kg/day DD. Patients received the treatment on days 1 through 5 of each 21-day course for up to 8 courses.
Patients were a median age of 59 years, two thirds had disease stage IIA or earlier, and 94% had received 3 or fewer prior therapies. Prior therapies included phototherapy (48%), interferon alfa (20%), electron beam readiotherapy (48%), system cytotoxic chemotherapy (26%), topical chemotherapy (25%), and other therapies (30%).
Most patients (85%) had mycosis fungoides, 6.3% had Sézary syndrome, and 8.3% had other cutaneous lymphomas.
After a median of 6 treatment courses, patients receiving either dose of DD had a statistically significant overall response rate (ORR) compared to placebo.
Patients in the 18 µg DD group had a 49% ORR, including 9% complete response (CR) or clinical complete response (CCR). This compared to an ORR of 16% for placebo patients (P=0.0015).
Patients in the 9 µg group had a 37.8% ORR, including 11% CR/CCR. This ORR was also significantly better compared to placebo (P=0.0297).
About half of the placebo patients experienced progressive disease compared with 21% of the DD-treated patients.
Progression-free survival (PFS) was significantly longer in the DD-treated patients. The 18 µg-arm had a median PFS of 971 days, the 9 µg-arm had a median PFS of 794 days, and the placebo patients had a median PFS of 124 days.
DD-treated patients in both dose groups experienced significantly superior duration of response, time to response, and time to treatment failure compared to the placebo patients.
DD-treated patients reported more adverse events and serious adverse events than the placebo patients. The investigators observed that the AEs occurred most frequently during the first 2 or 3 treatment courses and then declined to placebo levels.
DD combines the diphtheria toxin with human interleukin-2 (IL-2). DD binds to and is internalized by the IL-2 receptor. Therefore, it is most efficient at killing cells that express the intermediate- or high-affinity IL-2 receptor.
The investigators suggest that the 18 µg/kg/day dose may improve the response rate without increasing toxicity. The higher dose “provides more benefit, such as a higher ORR and statistically significant improvements in several supportive end points . . . DD may represent an important treatment option for many patients with these challenging diseases,” they said.
The recombinant fusion protein denileukin diftitox (DD) produced a significant and durable overall response rate at 2 dose levels as compared to placebo in patients with cutaneous T-cell lymphoma (CTCL).
These phase 3 results confirm the efficacy, safety, and clinical benefit of DD in CD25-positive, stage IA to III CTCL. An earlier trial included more heavily pretreated late-stage patients.
Andres Negro-Vilar, MD, PhD, and colleagues reported the current results March 8 ahead of print in the Journal of Clinical Oncology.
The investigators randomized 144 patients—44 to placebo, 45 to 9 mg/kg/day DD, and 55 to 18 m/kg/day DD. Patients received the treatment on days 1 through 5 of each 21-day course for up to 8 courses.
Patients were a median age of 59 years, two thirds had disease stage IIA or earlier, and 94% had received 3 or fewer prior therapies. Prior therapies included phototherapy (48%), interferon alfa (20%), electron beam readiotherapy (48%), system cytotoxic chemotherapy (26%), topical chemotherapy (25%), and other therapies (30%).
Most patients (85%) had mycosis fungoides, 6.3% had Sézary syndrome, and 8.3% had other cutaneous lymphomas.
After a median of 6 treatment courses, patients receiving either dose of DD had a statistically significant overall response rate (ORR) compared to placebo.
Patients in the 18 µg DD group had a 49% ORR, including 9% complete response (CR) or clinical complete response (CCR). This compared to an ORR of 16% for placebo patients (P=0.0015).
Patients in the 9 µg group had a 37.8% ORR, including 11% CR/CCR. This ORR was also significantly better compared to placebo (P=0.0297).
About half of the placebo patients experienced progressive disease compared with 21% of the DD-treated patients.
Progression-free survival (PFS) was significantly longer in the DD-treated patients. The 18 µg-arm had a median PFS of 971 days, the 9 µg-arm had a median PFS of 794 days, and the placebo patients had a median PFS of 124 days.
DD-treated patients in both dose groups experienced significantly superior duration of response, time to response, and time to treatment failure compared to the placebo patients.
DD-treated patients reported more adverse events and serious adverse events than the placebo patients. The investigators observed that the AEs occurred most frequently during the first 2 or 3 treatment courses and then declined to placebo levels.
DD combines the diphtheria toxin with human interleukin-2 (IL-2). DD binds to and is internalized by the IL-2 receptor. Therefore, it is most efficient at killing cells that express the intermediate- or high-affinity IL-2 receptor.
The investigators suggest that the 18 µg/kg/day dose may improve the response rate without increasing toxicity. The higher dose “provides more benefit, such as a higher ORR and statistically significant improvements in several supportive end points . . . DD may represent an important treatment option for many patients with these challenging diseases,” they said.