Kinetics of response to ipilimumab (MDX-010) in patients with stage III/IV melanoma.
2007 ASCO Annual Meeting
Journal of Clinical Oncology, 2007 ASCO Annual Meeting Proceedings Part I. Vol 25, No. 18S (June 20 Supplement), 2007: 8525
Author(s):
O. Hamid, W. J. Urba, M. Yellin, G. M. Nichol, J. Weber, E. M. Hersh, S. Tchekmedyian, F. S. Hodi, R. Weber, S. O'Day
Abstract:
Background: Ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4 (CTLA-4), enhances immune responses to tumor-associated antigens resulting in durable objective responses (OR). This abstract describes the kinetics of response after ipilimumab treatment.
Methods: 5 studies (2 complete; 3 ongoing) in 269 treated patients with stage III/IV melanoma were reviewed and analyzed to determine the kinetics and duration of response after ipilimumab. Patients received ipilimumab alone or with dacarbazine, IL-2 or gp100 peptide vaccine. Ipilimumab doses ranged from 0.3-10mg/kg/dose (single or multiple). Complete and partial response (CR, PR), stable and progressive disease (SD, PD) were evaluated.
Results: 41 patients (15%) had a confirmed OR at analysis. CR and PR was of late onset in some patients and occurred from ~10-106 and ~5-62 weeks (w) post-treatment initiation, respectively. In 28 patients onset of CR or PR occurred after >~12w of treatment. PD preceded OR (without additional therapy) in 4 patients. In 2 patients, PD measured at ~6w post-treatment initiation was followed by a PR at ~12w. In 1 patient the PR changed to a CR at ~24w and lasted for ~188w+; the other patient maintained a PR for ~17w. In the other 2 patients, PD at ~12w was followed by SD at ~17-20w and a PR after ~30 and 62w; PRs in both patients lasted for ~17 and 40w+, respectively. Duration of OR ranged from ~6-187w+; ORs are ongoing in 25 patients. Late onset occurred irrespective of dose, regimen and therapeutic partner.
Conclusions: Preliminary results suggest that ORs with ipilimumab may be later in onset and more durable than with traditional chemotherapy and may occur after progression. This late onset of effect likely reflects the immune-related mechanism of action of ipilimumab, and suggests that continued treatment/observation may be beneficial despite initial PD or SD. Acknowledgement: Dr. S. Rosenberg |
