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  • Open Access

Updated efficacy and toxicity of treatment with the anti-CTLA-4 antibody ipilimumab in metastatic melanoma patients previously treated with anti-PD-1 therapy

  • 1,
  • 2,
  • 3,
  • 4,
  • 1,
  • 1,
  • 5,
  • 6 and
  • 1
Journal for ImmunoTherapy of Cancer20153 (Suppl 2) :P126

https://doi.org/10.1186/2051-1426-3-S2-P126

  • Published:

Keywords

  • Stable Disease
  • Metastatic Melanoma
  • Melanoma Patient
  • Partial Remission
  • Ipilimumab

Background

Immunotherapy with anti-CTLA-4 and anti-PD-1 antibodies has demonstrated overall survival benefits in patients (pts) with metastatic melanoma (MM) compared to previous standard therapy. Two randomised clinical trials indicate that combined anti-CTLA-4 and anti-PD-1 antibody therapy increases the response rate compared to single agent treatment, but is associated with increased toxicity [1, 2]. Both efficacy and toxicity of anti-PD-1 therapy appear independent of prior treatment with the anti-CTLA-4 antibody ipilimumab. To date, only limited evidence exists regarding the efficacy and toxicity of Ipilimumab in pts that have progressed on treatment with an anti-PD-1 agent.

Methods

We retrospectively identified pts with MM who received anti-PD-1 therapy (Nivolumab/Pembrolizumab) and were subsequently treated with ipilimumab. Ipilimumab was administered at a dose of 3mg/kg every three weeks for (up to) four doses and response assessed by CT scan 4-6 weeks after the last dose. Efficacy and toxicity outcomes were determined from clinical records.

Results

The median age was 53 years with all pts having stage IVc disease and 4 pts (33%) with an elevated LDH at commencement of Ipilimumab dosing. The median time between the last dose of anti-PD-1 therapy and the commencement of Ipilimumab was 8 months (range 2-14 months). After a median follow-up of over 6 months, 1 patient (8%) achieved a partial remission as their best response to anti-PD-1 therapy with an additional 6 (50%) having stable disease. Five patients (42%) received all four doses of Ipilimumab. Two patients (17%) achieved an objective response to ipilimumab with another having prolonged stable disease. Four patients experienced grade 3/4 immune-related adverse events (irAE) including colitis (n=3) and pneumonitis (n=1).

Conclusions

Ipilimumab therapy can induce responses in patients who have failed treatment with an anti-PD-1 antibody. The response rate and clinical benefit rate appears similar compared to outcomes in pts who have not received prior anti-PD-1 antibody therapy. Although cases of severe and/or unusual irAEs such as pneumonitis have been observed, an analysis of a larger patient cohort will be required to test the significance of these observations.

Authors’ Affiliations

(1)
Medical Oncology, Austin Health, Heidelberg, Australia
(2)
Peter MacCallum Cancer Centre, East Melbourne, Australia
(3)
Princess Alexandra Hospital, Woolloongabba, Australia
(4)
Eastern Health Clinical School, Box Hill Hospital, Box Hill, Australia
(5)
Sir Charles Gairdner Hospital, Nedlands, Australia
(6)
Olivia Newton-John Cancer Research Institute, Heidelberg, Australia

References

  1. Postow MA, Chesney J, Pavlick AC, Robert C, Grossmann K, McDermott D, et al: Nivolumab and ipilimumab versus ipilimumab in untreated melanoma. N Engl J Med. 2015, 372: 2006-2017.PubMedView ArticleGoogle Scholar
  2. Larkin J, Chiarion-Sileni V, Gonzalez R, Grob JJ, Cowey CL, Lao CD, et al: Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015, 373: 23-34.PubMedView ArticleGoogle Scholar

Copyright

© Prithviraj et al. 2015

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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