Ipilimumab in advanced melanoma: reports of long-lasting responses

被引:49
作者
Farolfi, Alberto [1 ]
Ridolfi, Laura [1 ]
Guidoboni, Massimo [1 ]
Nicoletti, Stefania Vittoria Luisa [1 ]
Piciucchi, Sara [2 ]
Valmorri, Linda [3 ]
Costantini, Matteo [5 ]
Scarpi, Emanuela [3 ]
Amadori, Dino [4 ]
Ridolfi, Ruggero [1 ]
机构
[1] Canc Inst Romagna IRST, Immunotherapy & Somat Cell Therapy Unit, I-47014 Meldola, FC, Italy
[2] Canc Inst Romagna IRST, Radiol Unit, I-47014 Meldola, FC, Italy
[3] Canc Inst Romagna IRST, Unit Biostat & Clin Trials, I-47014 Meldola, FC, Italy
[4] Canc Inst Romagna IRST, Dept Med Oncol, I-47014 Meldola, FC, Italy
[5] Morgagni Pierantoni Hosp, Dept Pathol, Forli, Italy
关键词
advanced melanoma; anti-CTLA-4 monoclonal antibody therapy; immune-related response criteria; ipilimumab; melanoma treatment; predictive factors of response; T-LYMPHOCYTE ANTIGEN-4; DISTANT METASTATIC-DISEASE; UNRESECTABLE STAGE-III; MALIGNANT-MELANOMA; CLINICAL-RESPONSE; TUMOR-REGRESSION; ADVERSE EVENTS; IV MELANOMA; PHASE-I/II; BLOCKADE;
D O I
10.1097/CMR.0b013e328353e65c
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
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. Melanoma Res 22: 263-270 (C) 2012 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
引用
收藏
页码:263 / 270
页数:8
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