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Therapy with high-dose Interleukin-2 (HD IL-2) in metastatic melanoma and renal cell carcinoma following PD1 or PDL1 inhibition

Authors :
Elizabeth I. Buchbinder
Janice P. Dutcher
Gregory A. Daniels
Brendan D. Curti
Sapna P. Patel
Shernan G. Holtan
Gerald P. Miletello
Mayer N. Fishman
Rene Gonzalez
Joseph I. Clark
John M. Richart
Christopher D. Lao
Scott S. Tykodi
Ann W. Silk
David F. McDermott
Source :
Journal for ImmunoTherapy of Cancer, Vol 7, Iss 1, Pp 1-7 (2019)
Publication Year :
2019
Publisher :
BMJ Publishing Group, 2019.

Abstract

Abstract Background Metastatic melanoma (mM) and renal cell carcinoma (mRCC) are often treated with anti-PD-1 based therapy, however not all patients respond and further therapies are needed. High dose interleukin-2 (HD IL-2) can lead to durable responses in a subset of mM and mRCC patients. The efficacy and toxicity of HD IL-2 therapy following anti-PD-1 or anti-PD-L1 therapy have not yet been explored. Methods Reports on mM and mRCC patients who had received HD IL-2 after PD-1 or PD-L1 inhibition were queried from the PROCLAIM SM database. Patient characteristics, toxicity and efficacy were analyzed. Results A total of 57 patients (40 mM, 17 mRCC) were treated with high dose IL-2 after PD-1 or PD-L1 inhibition and had data recorded in the PROCLAIM database. The best overall response rate to HD IL-2 was 22.5% for mM (4 complete response (CR), 5 partial responses (PRs)) and 24% for mRCC (2 CRs, 2 PRs). The toxicity related to HD IL-2 observed in these patients was similar to that observed in patients treated with HD IL-2 without prior checkpoint blockade. One patient who had received prior PD-L1 blockade developed drug induced pneumonitis with HD IL-2 requiring steroid therapy. Conclusion In this retrospective analysis, HD IL-2 therapy displayed durable antitumor activity in mM and mRCC patients who progressed following treatment with PD-1 and PD-L1 inhibition. The toxicities were generally manageable and consistent with expectations from HD IL-2 but physicians should watch for immune related toxicities such as pneumonitis. This analysis supports the development of randomized prospective trials to assess the proper sequencing and combination of immune checkpoint blockade and cytokine therapy.

Details

Language :
English
ISSN :
20511426
Volume :
7
Issue :
1
Database :
Directory of Open Access Journals
Journal :
Journal for ImmunoTherapy of Cancer
Publication Type :
Academic Journal
Accession number :
edsdoj.2501d6126ef24a80bcbed81058801563
Document Type :
article
Full Text :
https://doi.org/10.1186/s40425-019-0522-3