| Abstract: |
BACKGROUND: Ipilimumab is a monoclonal antibody that antagonizes cytotoxic T lymphocyte antigen-4, a negative regulator of the immune system. The authors report on advanced refractory melanoma patients treated in a compassionate use trial of ipilimumab at theMemorial Sloan-Kettering Cancer Center. METHODS: Patientswith advanced refractory melanoma were treated in a compassionate use trial with ipilimumab 10mg/kg every 3 weeks for 4 doses.Those with evidence of clinical benefit atWeek 24 (complete response [CR], partial response [PR], or stable disease [SD]) then received ipilimumab every 12 weeks. RESULTS: A total of 53 patients were enrolled,with 51 evaluable. Grade 3/4 immune-related adverse events were noted in 29% of patients, with the most common immune-related adverse events being pruritus (43%), rash (37%), and diarrhea (33%). On the basis of immune-related response criteria, the response rate (CR + PR) was 12% (95% confidence interval [CI], 5%-25%), whereas 29% had SD (95% CI, 18%-44%). The median progression-free survival was 2.6 months (95% CI, 2.3-5.2 months), whereas the median overall survival (OS) was 7.2 months (95% CI, 4.0-13.3 months). Patients with an absolute lymphocyte count (ALC) ≥1000/μL after 2 ipilimumab treatments (Week 7) had a significantly improved clinical benefit rate (51% vs 0%; P = .01) andmedian OS (11.9 vs 1.4months; P < .001) comparedwith thosewith an ALC <1000/μL. CONCLUSIONS: The results confirm that ipilimumab is clinically active in patients with advanced refractory melanoma. The ALC after 2 ipilimumab treatments appears to correlate with clinical benefit and OS, and should be prospectively validated. © 2010 American Cancer Society. |
