Highlights
- •Ipilimumab 3 mg/kg after recurrence/progression on low-dose ipilimumab (IPI) has clinical activity.
- •The response rate was 9/36 (25%).
- •In primary resistance to low-dose IPI, the response rate was 6/20 (30%).
- •In acquired resistance to low-dose IPI, the response rate was 3/16 (18.5%).
- •This provides further evidence of the dose–efficacy relationship for IPI.
Abstract
Background
Differing doses of ipilimumab (IPI) are used in combination with an anti-PD1 antibody
in advanced melanoma. There is no data on the outcomes of patients who progress following
low-dose IPI (< 3 mg/kg) and are subsequently treated with IPI 3 mg/kg (IPI3). We
conducted a multicentre retrospective survey to assess the efficacy of this strategy.
Methods
Patients with resected stage III, unresectable stage III or IV melanoma who received
low dose IPI (< 3 mg/kg) with an anti-PD1 antibody with recurrence (neo/adjuvant)
or progressive disease (metastatic), who then received IPI3 ± anti-PD1 antibody were
eligible. Best investigator-determined Response Evaluation Criteria in Solid Tumours
response, progression-free survival (PFS) and overall survival (OS) were analysed.
Results
Total 36 patients received low-dose IPI with an anti-PD1 antibody, 18 (50%) in the
neo/adjuvant and 18 (50%) in the metastatic setting. Of which, 20 (56%) had primary
resistance and 16 (44%) had acquired resistance. All patients received IPI3 for unresectable
stage III or IV melanoma; median age 60 (29–78), 18 (50%) M1d disease, 32 (89%) Eastern
Cooperative Oncology Group performance status 0–1. Around 35 (97%) received IPI3 with
nivolumab and 1 received IPI3 alone. The response rate to IPI3 was 9/36 (25%). In
patients with primary resistance, the response rate was 6/20 (30%). After a median
follow-up of 22 months (95% CI: 15–27 months), the median PFS and OS were not reached
in patients who responded; 1-year PFS and OS were 73% and 100%, respectively.
Conclusions
IPI3 following recurrence/progression on low dose IPI has clinical activity, including
in primary resistance. IPI dosing is therefore critical in a subset of patients.
Keywords
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Article info
Publication history
Published online: March 10, 2023
Accepted:
March 4,
2023
Received in revised form:
February 15,
2023
Received:
December 11,
2022
Publication stage
In Press Uncorrected ProofIdentification
Copyright
© 2023 Elsevier Ltd. All rights reserved.
