Immunological and biological changes during ipilimumab treatment and their potential correlation with clinical response and survival in patients with advanced melanoma.
BACKGROUND
Ipilimumab can induce durable disease control and long-term survival in patients with metastatic melanoma. Identification of a biomarker that correlates with clinical benefit and potentially provides an early marker of response is an active area of research.


METHODS
Ipilimumab was available upon physician request for patients aged ≥16 years with stage III (unresectable) or IV cutaneous, ocular or mucosal melanoma, who had failed or did not tolerate previous treatments and had no other therapeutic option available. Patients received ipilimumab 3 mg/kg every 3 weeks for four doses. Tumour assessments were conducted at baseline, Week 12 and Week 24 using immune-related response criteria. Patients were monitored continuously for adverse events (AEs), including immune-related AEs. Candidate immunological markers were evaluated in peripheral blood and sera samples collected at baseline and Weeks 4, 7, 10 and 12.


RESULTS
Among 95 patients treated with ipilimumab 3 mg/kg, the immune-related disease control rate at Week 24 was 38 %. With a median follow-up of 24 months, median overall survival was 9.6 months. Both disease control and survival were significantly associated with decreasing levels of lactate dehydrogenase, C-reactive protein and FoxP3/regulatory T cells, and increasing absolute lymphocyte count, between baseline and the end of dosing (Week 12).


CONCLUSIONS
Ipilimumab is a feasible treatment option for heavily pretreated patients with metastatic melanoma. Changes in some immunological markers between baseline and the fourth ipilimumab infusion appear to be associated with disease control and survival, but verification in prospective clinical trials is required.
Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, IRCCS, Istituto Nazionale Tumori Fondazione "G. Pascale", Via Mariano Semmola, 80131, Naples, Italy.
Ester
E
Simeone
Giusy
G
Gentilcore
Diana
D
Giannarelli
Antonio M
AM
Grimaldi
Corrado
C
Caracò
Marcello
M
Curvietto
Assunta
A
Esposito
Miriam
M
Paone
Marco
M
Palla
Ernesta
E
Cavalcanti
Fabio
F
Sandomenico
Antonella
A
Petrillo
Gerardo
G
Botti
Franco
F
Fulciniti
Giuseppe
G
Palmieri
Paola
P
Queirolo
Paolo
P
Marchetti
Virginia
V
Ferraresi
Gaetana
G
Rinaldi
Maria Pia
MP
Pistillo
Gennaro
G
Ciliberto
Nicola
N
Mozzillo
Paolo A
PA
Ascierto
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D005134:Eye Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D005260:Female; D006801:Humans; D000074324:Ipilimumab; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D008875:Middle Aged; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D016019:Survival Analysis; D016896:Treatment Outcome; D055815:Young Adult
D000911:Antibodies, Monoclonal; D000074324:Ipilimumab