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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2019-02-18

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

ABSTRACT

BackgroundMetastatic 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.MethodsReports on mM and mRCC patients who had received HD IL-2 after PD-1 or PD-L1 inhibition were queried from the PROCLAIMSM database. Patient characteristics, toxicity and efficacy were analyzed.ResultsA 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.ConclusionIn 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. More... »

PAGES

49

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s40425-019-0522-3

DOI

http://dx.doi.org/10.1186/s40425-019-0522-3

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1112212877

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30777131


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27 schema:description BackgroundMetastatic 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.MethodsReports on mM and mRCC patients who had received HD IL-2 after PD-1 or PD-L1 inhibition were queried from the PROCLAIMSM database. Patient characteristics, toxicity and efficacy were analyzed.ResultsA 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.ConclusionIn 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.
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33 schema:keywords ConclusionIn
34 HD IL-2
35 HD IL-2 therapy
36 IL-2
37 IL-2 therapy
38 L1 therapy
39 MethodsReports
40 PD-1
41 PD-L1 blockade
42 PD-L1 inhibition
43 PD1
44 ResultsA total
45 activity
46 analysis
47 antitumor activity
48 best overall response rate
49 blockade
50 carcinoma
51 cell carcinoma
52 characteristics
53 checkpoint blockade
54 combination
55 data
56 database
57 development
58 dose IL-2
59 dose interleukin-2
60 drugs
61 durable antitumor activity
62 durable responses
63 efficacy
64 expectations
65 further therapy
66 high-dose IL-2
67 high-dose interleukin-2
68 immune checkpoint blockade
69 immune related toxicities
70 inhibition
71 interleukin-2
72 mM
73 mRCC
74 mRCC patients
75 melanoma
76 metastatic melanoma
77 overall response rate
78 patient characteristics
79 patients
80 physicians
81 pneumonitis
82 proper sequencing
83 prospective trial
84 rate
85 related toxicity
86 renal cell carcinoma
87 response
88 response rate
89 retrospective analysis
90 sequencing
91 steroid therapy
92 subset
93 therapy
94 total
95 toxicity
96 treatment
97 trials
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