1117PD - Long term survival and immunological correlates in metastatic melanoma treated with ipilimumab at 10 mgs within an expanded access program

Date 29 September 2012
Event ESMO Congress 2012
Session Melanoma
Topics Cancer Immunology and Immunotherapy
Melanoma and other Skin Tumours
Presenter Anna Maria Di Giacomo
Authors A.M. Di Giacomo1, L. Calabrò2, R. Danielli3, I. Pesce4, E. Fonsatti4, E. Bertocci4, D. Giannarelli5, M. Biagioli6, M. Altomonte4, M. Maio7
  • 1Medical Oncology and Immunotherapy,University Hospital of Siena, 53100 - Siena/IT
  • 2Department Of Oncology, Medical Oncology and Immunotherapy,University Hospital of Siena, Siena/IT
  • 3Medical Oncology And Immunotherapy, Medical Oncology and Immunotherapy,University Hospital of Siena, 53100 - Siena/IT
  • 4Department Of Oncology, Medical Oncology and Immunotherapy,University Hospital of Siena, 53100 - Siena/IT
  • 5Medical Oncology, Regina Elena National Cancer Institute, Roma/IT
  • 6Department Of Medicine, Dermatology, University Hospital of Siena, Siena/IT
  • 7Division Of Medical Oncology And Immunotherapy, Medical Oncology and Immunotherapy,University Hospital of Siena, 53100 - Siena/IT

 

Abstract

Background

Ipilimumab (IPI) has shown long lasting responses in metastatic melanoma (MM) patients (pts) in phase II/III trials (Hodi et al., NEJM 2010; Robert et al. NEJM 2011; Prieto et al., CCR 2012). We have previously reported a significant clinical efficacy of IPI in 27 heavily pre-treated MM pts enrolled within the 10 mgs expanded access program (EAP) available at the University Hospital of Siena; one and 2-years survival were 34.8% and 23.5%, respectively (Di Giacomo, et al. CII, 2010). In spite of its clinical efficacy, no definitive predictive markers of response have been identified yet. We report here the survival follow-up of this cohort of MM pts and preliminary data on immunological correlates.

Methods

Twenty-seven pts with stage III (2) or IV (25) MM, progressing to a median of 3 (1-5) systemic therapies, were treated according to the EAP with IPI at 10 mg/Kg i.v. given at weeks (wks) 1, 4, 7, 10 during the induction phase, and every 12 wks from W24 in the maintenance phase. Peripheral blood mononuclear cells were collected from 17 pts at baseline, W7, W12 and W24 and analyzed by flow cytometry for ICOS expression on both CD4 and CD8+ T cells. The ratio between absolute blood neutrophils (N) and lymphocytes (L) count was determined at baseline, W4, W7 and W10 for 27, 27, 24 and 23 pts, respectively.

Results

With a median follow-up of 9.6 months the median OS was 9.6 months (95% CI: 4.2-16.1; range: 3.1-51.2; three and 4-years survival rates were 20.9%, with 5 long-term survivors (>4 yrs). A significant (p < 0.05) increase in the percentage and absolute number of CD4 + ICOS+ and CD8 + ICOS+ circulating T cells was observed from W7 on. Compared to baseline, pts with a fold increase in CD4 + ICOS+ and CD8 + ICOS+ T cells higher than 4 at W7 and W12 experienced a clinical benefit (SD, PR and CR). Pts with a N/L ratio lower than median at W7 and W10 had a significantly better survival.

Conclusions

ipi can induce long-term survivals in heavily pre-treated MM pts. Circulating ICOS+ T cells and N/L ratio in the course of treatment with ipi may represent predictive markers of clinical effectiveness in the daily practice.

Disclosure

M. Maio: Advisory Board and Honoraria from Bristol-Myers Squibb and Roche.

All other authors have declared no conflicts of interest.