Single-institution experience with ipilimumab in advanced melanoma patients in the compassionate use setting: lymphocyte count after 2 doses correlates with survival.
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 the Memorial Sloan-Kettering Cancer Center.


METHODS
: Patients with advanced refractory melanoma were treated in a compassionate use trial with ipilimumab 10 mg/kg every 3 weeks for 4 doses. Those with evidence of clinical benefit at Week 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) > micro =1000/microL after 2 ipilimumab treatments (Week 7) had a significantly improved clinical benefit rate (51% vs 0%; P = .01) and median OS (11.9 vs 1.4 months; P < .001) compared with those with an ALC <1000/microL.


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. Cancer 2010. (c) 2010 American Cancer Society.
Ludwig Center for Cancer Immunotherapy, Memorial Sloan-Kettering Cancer Center, New York, New York, USA.
Geoffrey Y
GY
Ku
Jianda
J
Yuan
David B
DB
Page
Sebastian E A
SE
Schroeder
Katherine S
KS
Panageas
Richard D
RD
Carvajal
Paul B
PB
Chapman
Gary K
GK
Schwartz
James P
JP
Allison
Jedd D
JD
Wolchok
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor; D057176:Compassionate Use Trials; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D018655:Lymphocyte Count; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D019233:Retreatment; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology
D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D000074324:Ipilimumab