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. 2019 Feb 18;7(1):49.
doi: 10.1186/s40425-019-0522-3.

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

Elizabeth I Buchbinder  1 , Janice P Dutcher  2 , Gregory A Daniels  3 , Brendan D Curti  4 , Sapna P Patel  5 , Shernan G Holtan  6 , Gerald P Miletello  7 , Mayer N Fishman  8 , Rene Gonzalez  9 , Joseph I Clark  10 , John M Richart  11 , Christopher D Lao  12 , Scott S Tykodi  13 , Ann W Silk  14 , David F McDermott  15
Affiliations

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

Elizabeth I Buchbinder et al. J Immunother Cancer. .

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 PROCLAIMSM 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.

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the institutional review boards of the sites enrolling subjects and all patients provided written, informed consent.

Consent for publication

Not applicable.

Competing interests

EB receives clinical trial support from BMS and Merck, JD receives consulting income from Prometheus, BMS, Tracon, Iovance, Eisai, Merck, and Amgen, SH receives consulting income from Incyte, AS receives clinical trial support from BMS and Merck and receives consulting income from Merck. JC receives consulting income from BMS and Merck. ST receives clinical trial support from Peloton Therapeutics, Merck, Nektar Therapeutics, Calithera Biosciences, Jounce Therapeutics Pfizer, Genentech, ARGOS Therapeutics and BMS, he also receives consulting honoraria from Calithera Biosciences, Prometheus Laboratories and Bristol-Myers Squibb. GD, BC, SP, SH, GM, MF, RG, JC, JR, CL ST, AS and DM all receive institutional research funding from Prometheus. DM receives consulting honoraria from BMS, Pfizer, Merck, Novartis, Eisai, Exelixis, Array, Genentech and Jounce.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Overall Survival in months for patients treated with IL-2 alone or IL-2 following PD-1 inhibition in metastatic melanoma (a) and metastatic renal cell carcinoma (b)
Fig. 2
Fig. 2
Progression-Free Survival in months for patients treated with IL-2 alone or IL-2 following PD-1 inhibition in metastatic melanoma (a) and metastatic renal cell carcinoma (b)
See this image and copyright information in PMC

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References

    1. Atkins, M.B., et al., High-dose recombinant interleukin 2 therapy for patients with metastatic melanoma: analysis of 270 patients treated between 1985 and 1993. J Clin Oncol, 1999. 17(7): p. 2105–2116. - PubMed
    1. Fyfe G, et al. Results of treatment of 255 patients with metastatic renal cell carcinoma who received high-dose recombinant interleukin-2 therapy. J Clin Oncol. 1995;13(3):688–696. doi: 10.1200/JCO.1995.13.3.688. - DOI - PubMed
    1. Clark J, Curti BD, Davis E, Kaufman H, Amin A, Alva A, Logan T, Hauke R, Miletello G, Vaishampayan U, Johnson D, White R, Wiernik P, Dutcher J. Long-term disease-free survival (DFS) of metastatic melanoma (mM) and renal cell cancer (mRCC) patients following high-dose interleukin-s (HD IL2) JITC. 2017;5(Suppl 2):P319. - PMC - PubMed
    1. Kammula US, White DE, Rosenberg SA. Trends in the safety of high dose bolus interleukin-2 administration in patients with metastatic cancer. Cancer. 1998;83(4):797–805. doi: 10.1002/(SICI)1097-0142(19980815)83:4<797::AID-CNCR25>3.0.CO;2-M. - DOI - PubMed
    1. Hodi FS, et al. Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010;363(8):711–723. doi: 10.1056/NEJMoa1003466. - DOI - PMC - PubMed

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