title: Ipilimumab in advanced melanoma:  reports of long-lasting responses.
abstract: Patients with metastatic melanoma have a poor prognosis; the results of chemotherapy remain unsatisfactory. Ipilimumab, an anticytotoxic T lymphocyte-associated antigen-4 antibody, has shown promising results in several clinical trials. In this report, advanced melanoma patients receiving ipilimumab were scored according to novel immune-related response criteria (irRC) in an attempt to capture additional response patterns and to avoid premature treatment cessation. Thirty-six heavily pretreated metastatic melanoma patients recieved ipilimumab within five international clinical trials at our Institution from May 2006 to August 2008. Disease progression was defined as an increase in tumor burden by at least 25% compared with the nadir, irrespective of any initial increase in baseline lesions or the appearance of new lesions. We report unusually long-lasting responses in patients treated with ipilimumab 10 mg/kg. An overall response was observed in six out of 30 patients (20%), a complete response in three (10%), and disease control in 11 (37%), which seemed to be of a long duration (median of 16 months; complete response 36+, 34+, and 41+ months). All irRC patterns seemed to be strongly associated with an improvement in overall survival. Interestingly, we found a correlation between the presence of a grade 3/4 immune-related adverse event and responses, time to progression, and overall survival. Ipilimumab therapy resulted in clinically meaningful responses in advanced melanoma patients, supporting the need for further irRC validation.
authors.affiliation: Immunotherapy and Somatic Cell Therapy Unit bRadiology Unit, Cancer Institute of Romagna, Meldola, FC, Italy.
authors.forename: Alberto
authors.initials: A
authors.lastname: Farolfi
authors.forename: Laura
authors.initials: L
authors.lastname: Ridolfi
authors.forename: Massimo
authors.initials: M
authors.lastname: Guidoboni
authors.forename: Stefania Vittoria Luisa
authors.initials: SV
authors.lastname: Nicoletti
authors.forename: Sara
authors.initials: S
authors.lastname: Piciucchi
authors.forename: Linda
authors.initials: L
authors.lastname: Valmorri
authors.forename: Matteo
authors.initials: M
authors.lastname: Costantini
authors.forename: Emanuela
authors.initials: E
authors.lastname: Scarpi
authors.forename: Dino
authors.initials: D
authors.lastname: Amadori
authors.forename: Ruggero
authors.initials: R
authors.lastname: Ridolfi
mesh_terms: D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D017322:Clinical Trials, Phase II as Topic; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy / Q000009:adverse effects / Q000379:methods*; D000074324:Ipilimumab; D007558:Italy; D053208:Kaplan-Meier Estimate; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D008875:Middle Aged; D009367:Neoplasm Staging; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D000074324:Ipilimumab