Aim
Immune checkpoint inhibitors have become the standard treatments for metastatic melanoma. Serious immune-related adverse events are common. We reviewed our experience with ipilimumab to document overall survival rate at 2 years, factors associated with improved outcomes and immune related adverse events (irAEs).
Methods
We conducted retrospective analysis of 43 patients treated with ipilimumab for metastatic melanoma at Royal Adelaide Hospital between July 2010 and December 2013. Data was collected on patient demographics, treatment history, BRAF mutation status, baseline LDH, change in lymphocyte counts, brain metastases and grade 3/4 irAEs. A Kaplan Meier survival analysis was performed.
Results
The estimated median OS was 9 months and the 2 year survival rate was 14%. At a median follow up of 66 months, a plateau in survival curve seemed evident at 3 years. Median PFS was 5 months and median TTF was 4 months.
Age (P<0.001, HR 0.94, 95% CI 0.9-0.97), increase in lymphocyte count from baseline to after 2 cycles of ipilimumab (P<0.009, HR 0.40, 95% CI 0.2-0.8), absence of brain metastases (P<0.002, HR 0.1, 95% CI 0.02-0.42) and subsequent treatment after ipilimumab (P<0.00, HR 0.08, 95% CI 0.02-0.3) were associated with improved survival. Baseline LDH, prior treatment, blood eosinophilia and BRAF mutation status did not affect overall survival.
Activity of ipilimumab in patients with brain metastases was also noted with median survival of 23 months.
Out of 15 patients (35%) who experienced grade 3/4 irAEs, GI toxicity was most common. One patient with retinopathy, one with Guillain Barre Syndrome, two with colitis and hypophysitis are still alive, indicating possible relationship between grade 3/4 irAEs and survivability.
Conclusion
At a single Australian institution, ipilimumab has shown efficacy and tolerability similar to those seen in pivotal clinical trials. Grade 3 and 4 toxicities were common and prognostic markers may indicate those most likely to benefit.