Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma

Elaine T. Lam, Michael K K Wong, Neeraj Agarwal, Bruce G. Redman, Theodore Logan, Dexiang Gao, Thomas W. Flaig, Karl Lewis, Jamie Poust, Paul Monk, Anthony Jarkowski, Arun Sendilnathan, Marcus Bolden, Timothy M. Kuzel, Thomas Olencki

Research output: Contribution to journalArticle

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Abstract

Although tyrosine kinase inhibitors (TKI) are the most common first-line therapy for metastatic renal cell carcinoma, high-dose interleukin-2 (HD-IL2) remains the only agent that provides durable complete responses. The optimal sequence of these agents remains uncertain. This retrospective multi-institutional study examined the safety and efficacy of HD-IL2 following TKI therapy. After IRB approval at 7 HD-IL2 centers, data relating to patient, disease, and treatment characteristics among 40 consecutive patients with metastatic renal cell carcinoma who were treated with HD-IL2 after at least 1 prior TKI therapy were retrospectively collected. The most common cardiac adverse events were grade 3 hypotension and vascular leak syndrome. Six patients (15%) experienced other grade ≥3 cardiac adverse events. There were 2 treatment-related deaths due to congestive heart failure, occurring in 1 patient with short TKI to HD-IL2 interval and another patient with an abnormal baseline cardiac stress test. Best responses included 2 CRs (5%, duration 40+ and 62+ mo), 3 PRs (8%, duration 6, 11, and 24 mo), 13 SD (32%, median duration 12 mo), 20 PD (50%), and 2 not evaluable patients. Median overall survival was 22 months. Administration of HD-IL2 could be safe and effective after TKI therapy; however, careful selection of patients is critical. We recommend baseline cardiac risk factor assessment, screening with both cardiac stress test and echocardiogram, and allowing a TKI to HD-IL2 interval of at least 2 months.

Original languageEnglish
Pages (from-to)360-365
Number of pages6
JournalJournal of Immunotherapy
Volume37
Issue number7
DOIs
StatePublished - 2014

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Renal Cell Carcinoma
Protein-Tyrosine Kinases
Interleukin-2
Safety
Exercise Test
Therapeutics
Research Ethics Committees
Hypotension
Patient Selection
Heart Failure
Survival

Keywords

  • high-dose interleukin-2
  • renal cell carcinoma
  • sorafenib
  • sunitinib
  • tyrosine kinase inhibitor (TKI)

ASJC Scopus subject areas

  • Immunology
  • Immunology and Allergy
  • Cancer Research
  • Pharmacology
  • Medicine(all)

Cite this

Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma. / Lam, Elaine T.; Wong, Michael K K; Agarwal, Neeraj; Redman, Bruce G.; Logan, Theodore; Gao, Dexiang; Flaig, Thomas W.; Lewis, Karl; Poust, Jamie; Monk, Paul; Jarkowski, Anthony; Sendilnathan, Arun; Bolden, Marcus; Kuzel, Timothy M.; Olencki, Thomas.

In: Journal of Immunotherapy, Vol. 37, No. 7, 2014, p. 360-365.

Research output: Contribution to journalArticle

Lam, ET, Wong, MKK, Agarwal, N, Redman, BG, Logan, T, Gao, D, Flaig, TW, Lewis, K, Poust, J, Monk, P, Jarkowski, A, Sendilnathan, A, Bolden, M, Kuzel, TM & Olencki, T 2014, 'Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma', Journal of Immunotherapy, vol. 37, no. 7, pp. 360-365. https://doi.org/10.1097/CJI.0000000000000044
Lam, Elaine T. ; Wong, Michael K K ; Agarwal, Neeraj ; Redman, Bruce G. ; Logan, Theodore ; Gao, Dexiang ; Flaig, Thomas W. ; Lewis, Karl ; Poust, Jamie ; Monk, Paul ; Jarkowski, Anthony ; Sendilnathan, Arun ; Bolden, Marcus ; Kuzel, Timothy M. ; Olencki, Thomas. / Retrospective analysis of the safety and efficacy of high-dose interleukin-2 after prior tyrosine kinase inhibitor therapy in patients with advanced renal cell carcinoma. In: Journal of Immunotherapy. 2014 ; Vol. 37, No. 7. pp. 360-365.
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AU - Monk, Paul

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