scholarly journals Radiotherapy and High-Dose Interleukin-2: Clinical and Immunological Results of a Proof of Principle Study in Metastatic Melanoma and Renal Cell Carcinoma

2021 ◽  
Vol 12 ◽  
Author(s):  
Jenny Bulgarelli ◽  
Claudia Piccinini ◽  
Elisabetta Petracci ◽  
Elena Pancisi ◽  
Anna Maria Granato ◽  
...  

High-dose interleukin-2 (HD IL-2) has curative potential in metastatic melanoma (MM) and renal cell carcinoma (RCC). Radiotherapy (RT) kills cancer cells and induces immunomodulatory effects. Prospective trials exploring clinical and immunological properties of combined RT/HD IL-2 are still needed. We designed a phase II, single-arm clinical trial for patients with MM and RCC. The treatment schedule consisted of 3 daily doses of 6-12 Gy of RT to 1-5 non-index metastatic fields, before IL-2 at the first and third treatment cycle. HD IL-2 was administered by continuous infusion for 72 hours and repeated every 3 weeks for up to 4 cycles, thereafter every 4 weeks for a maximum of 2 cycles. The primary endpoint was the immunological efficacy of the combined RT/HD IL-2 treatment (assessed by IFN-γ ELISPOT). Nineteen out of 22 patients were evaluable for immunological and clinical response. Partial response occurred in 3 (15.7%) patients and stable disease was observed in 7 (36.8%). The disease control rate was 52.6% after a median follow up of 39.2 months. According to Common Terminology Criteria for Adverse Events 4.0 (CTCAE 4.0), the majority of toxicities were grade 1-2. Immunological responses were frequent and detected in 16 (84.2%) patients. Increased levels of IL-8 and IL-10 in melanoma, circulating effector memory CD4+ and intratumoral CD8+ T cells in both tumor types were detected after therapy. Overall the treatment was well tolerated and immunologically active. Immunomonitoring and correlative data on tumor and peripheral blood cell subsets suggest that this combination treatment could be a promising strategy for patients progressing after standard treatments.

2021 ◽  
Vol 69 (4) ◽  
pp. 888-892
Author(s):  
Joseph I Clark ◽  
Brendan Curti ◽  
Elizabeth J Davis ◽  
Howard Kaufman ◽  
Asim Amin ◽  
...  

High-dose interleukin-2 (HD IL-2) was approved in the 1990s after demonstrating durable complete responses (CRs) in some patients with metastatic melanoma (mM) and metastatic renal cell carcinoma (mRCC). Patients who achieve this level of disease control have also demonstrated improved survival compared with patients who progress, but limited data are available describing the long-term course. The aim of this study was to better characterize long-term survival following successful HD IL-2 treatment in patients with no subsequent systemic therapy. Eleven HD IL-2 treatment centers identified patients with survival ≥5 years after HD IL-2, with no subsequent systemic therapy. Survival was evaluated from the date of IL-2 treatment to June 2017. Treatment courses consisted of 2 1-week cycles of HD IL-2. Patients were treated with HD IL-2 alone, or HD IL-2 followed by local therapy to achieve maximal response. 100 patients are reported: 54 patients with mM and 46 patients with mRCC. Progression-free survival (PFS) after HD IL-2 ranges from 5+ years to 30+ years, with a median follow-up of 10+ years. 27 mRCC and 32 mM are alive ≥10 years after IL-2. Thus, a small subset of patients with mM and mRCC achieve long-term PFS (≥5 years) after treatment with HD IL-2 as their only systemic therapy. The ability of HD IL-2 therapy to induce prolonged PFS should be a major consideration in studies of new immunotherapy combinations for mM and mRCC.


2014 ◽  
Vol 32 (15_suppl) ◽  
pp. e20055-e20055
Author(s):  
Jeremy D. Whyman ◽  
Whitney Hitchcock ◽  
Spencer L. James ◽  
Joseph J. Shatzel ◽  
Marc S. Ernstoff

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. e14007-e14007 ◽  
Author(s):  
Laura Ridolfi ◽  
Francesco De Rosa ◽  
Anna Maria Granato ◽  
Elena Pancisi ◽  
Jenny Bulgarelli ◽  
...  

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e21006-e21006 ◽  
Author(s):  
Elizabeth Iannotti Buchbinder ◽  
Janice P. Dutcher ◽  
Jessica C. Perritt ◽  
Joseph Clark ◽  
Shernan G. Holtan ◽  
...  

2005 ◽  
Vol 12 (5) ◽  
pp. 381-390 ◽  
Author(s):  
Kathryn Spanknebel ◽  
Kenneth Y. Cheung ◽  
John Stoutenburg ◽  
Karl Hurst-Wicker ◽  
Charles Hesdorffer ◽  
...  

Cancer ◽  
1994 ◽  
Vol 74 (12) ◽  
pp. 3212-3222 ◽  
Author(s):  
Richard L. White ◽  
Douglas J. Schwartzentruber ◽  
Anshu Guleria ◽  
Mark P. Macfarlane ◽  
Donald E. White ◽  
...  

2019 ◽  
Vol 37 (8_suppl) ◽  
pp. 14-14
Author(s):  
Stephanie A. Berg ◽  
Joseph I. Clark ◽  
Elizabeth Henry ◽  
Courtney Regan Wagner ◽  
Robert Charles Flanigan ◽  
...  

14 Background: Approved treatments for metastatic melanoma (MM) and metastatic renal cell carcinoma (mRCC) include targeted agents, high dose interleukin-2 (HD IL-2) and checkpoint inhibitors (CI). A subset of responders to HD-IL2 can achieve long term durable remissions (7-10%). Recently, data suggests that durable remissions are possible with CI. Thus, despite increased toxicity, first-line immunotherapy with HD-IL2 is a reasonable consideration in carefully selected patients with clear cell mRCC and MM followed by CI upon relapse. Our study explores the utility and safety of CI subsequent to HD-IL2 in patients (pts) in this population. Methods: We conducted a single institution retrospective analysis of pts with MM or mRCC who received HD-IL2 and subsequent CI from 2008-2017. Pts treated with prior targeted therapy were included. Statistical analysis was performed using Fischer's exact tests, log-rank test for KM analysis and non-parametric Wilcoxon Rank Sum tests to compare the groups. Results: We identified 34 unique pts (19 MM, 15 mRCC) from our pre-specified cohort. Pts were male (73%), Caucasian (88%), and median age=53. mRCC pts received more cancer related treatments than MM prior to CIs after HD-IL2 was given (2 vs. 1, p=0.002), had more total CI cycles administered (12 vs. 7, p=0.10) but less IL-2 doses than MM pts (20 vs. 24, p=0.26). mRCC pts tended to record higher HD-IL2 toxicity grade compared to MM pts (exact =0.04). 26% (9/34) of pts experienced a grade 2 or higher CI toxicity. Pts had higher HD IL-2 toxicities than CI toxicities during therapy but these two measures were not significantly correlated (r=0.07, p=0.73); furthermore, there was no survival difference between pts with reported grade 2 or higher CI toxicity compared to pts without any CI toxicity ( p=0.14). Conclusions: Our study suggests that CI therapy after HD-IL2 is feasible and not associated with more frequent toxicity or less clinical efficacy in pts with MM or mRCC.


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