73P - Development of circulating anti-drug antibodies associate with shortened survival in patients with metastatic malignant melanoma treated with ipili...

Date 08 December 2017
Event ESMO Immuno-Oncology Congress 2017
Session Lunch & Poster Display session
Topics Central Nervous System Malignancies
Presenter Anders Kverneland
Citation Annals of Oncology (2017) 28 (suppl_11): xi6-xi29. 10.1093/annonc/mdx711
Authors A. Kverneland
  • Center For Cancer Immune Therapy, Department Of Haematology And Department Of Oncology, Herlev and Gentofte Hospital, 2730 - Herlev/DK

Abstract

Background

Checkpoint inhibitors including the CTLA-4 blocking antibody ipilimumab have become the new standard therapy of many metastatic cancers. Development of anti-drug antibodies (ADAs) after treatment with other biopharmaceuticals has been thoroughly investigated, but induction of ADAs after treatment with checkpoint inhibitors is poorly investigated. In this retrospective study, we measured ipilimumab serum levels and anti-ipilimumab antibody levels in patients with unresectable or metastatic melanoma (MM), and related the findings to clinical outcome.

Methods

Serum samples from 31 patients with MM were analyzed for ADAs against ipilimumab and serum levels of ipilimumab at baseline, after 1st infusion and 3rd infusion using an in-house developed bead-based assay. Data were correlated with progression-free survival (PFS) and overall survival (OS).

Results

Low serum levels of ipilimumab after 1st infusion correlated significantly to a shorter OS (p = 0.024) but not PFS, and this correlation was not observed after 3rd infusion. Seven patients (23%) were ADA-positive after 1st infusion, three of whom were excluded before the 3rd infusion due to disease progression. Five patients (19%) were ADA-positive after the 3rd infusion. Patients with a positive ADA status after 1st infusion had shorter PFS (p = 0.0186) and OS (p = 0.0143) than ADA-negative patients, while ADA-positivity after the 3rd infusion did not correlate significantly with PFS or OS. ADA status did not correlate with serum levels of ipilimumab.

Conclusions

Low serum levels of ipilimumab after 1st infusion is correlated with shorter OS, while ADA-positivity is associated with shorter OS as well as PFS in patients with MM.

Clinical trial identification

Legal entity responsible for the study

Inge Marie Svane

Funding

None

Disclosure

All authors have declared no conflicts of interest.