Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry

Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response. Ausführliche Beschreibung

Gespeichert in:

Autor*in:	Curti, Brendan [verfasserIn] Daniels, Gregory A. McDermott, David F. Clark, Joseph I. Kaufman, Howard L. Logan, Theodore F. Singh, Jatinder Kaur, Meenu Luna, Theresa L. Gregory, Nancy Morse, Michael A. Wong, Michael K. K. Dutcher, Janice P.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2017

Schlagwörter:	Immune-related adverse events Interleukin-2 Renal cell carcinoma Melanoma Survival PROCLAIM

Anmerkung:	© The Author(s). 2017

Übergeordnetes Werk:	Enthalten in: Journal for ImmunoTherapy of Cancer - London : BioMed Central, 2013, 5(2017), 1 vom: 19. Dez.
Übergeordnetes Werk:	volume:5 ; year:2017 ; number:1 ; day:19 ; month:12

Links:	Volltext

DOI / URN:	10.1186/s40425-017-0307-5

Katalog-ID:	SPR036436348

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100	1		\|a Curti, Brendan \|e verfasserin \|4 aut
245	1	0	\|a Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry
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520			\|a Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response.
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allfields	10.1186/s40425-017-0307-5 doi (DE-627)SPR036436348 (SPR)s40425-017-0307-5-e DE-627 ger DE-627 rakwb eng Curti, Brendan verfasserin aut Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response. Immune-related adverse events (dpeaa)DE-He213 Interleukin-2 (dpeaa)DE-He213 Renal cell carcinoma (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Survival (dpeaa)DE-He213 PROCLAIM (dpeaa)DE-He213 Daniels, Gregory A. aut McDermott, David F. aut Clark, Joseph I. aut Kaufman, Howard L. aut Logan, Theodore F. aut Singh, Jatinder aut Kaur, Meenu aut Luna, Theresa L. aut Gregory, Nancy aut Morse, Michael A. aut Wong, Michael K. K. aut Dutcher, Janice P. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 5(2017), 1 vom: 19. Dez. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:5 year:2017 number:1 day:19 month:12 https://dx.doi.org/10.1186/s40425-017-0307-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2017 1 19 12
spelling	10.1186/s40425-017-0307-5 doi (DE-627)SPR036436348 (SPR)s40425-017-0307-5-e DE-627 ger DE-627 rakwb eng Curti, Brendan verfasserin aut Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response. Immune-related adverse events (dpeaa)DE-He213 Interleukin-2 (dpeaa)DE-He213 Renal cell carcinoma (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Survival (dpeaa)DE-He213 PROCLAIM (dpeaa)DE-He213 Daniels, Gregory A. aut McDermott, David F. aut Clark, Joseph I. aut Kaufman, Howard L. aut Logan, Theodore F. aut Singh, Jatinder aut Kaur, Meenu aut Luna, Theresa L. aut Gregory, Nancy aut Morse, Michael A. aut Wong, Michael K. K. aut Dutcher, Janice P. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 5(2017), 1 vom: 19. Dez. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:5 year:2017 number:1 day:19 month:12 https://dx.doi.org/10.1186/s40425-017-0307-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2017 1 19 12
allfields_unstemmed	10.1186/s40425-017-0307-5 doi (DE-627)SPR036436348 (SPR)s40425-017-0307-5-e DE-627 ger DE-627 rakwb eng Curti, Brendan verfasserin aut Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response. Immune-related adverse events (dpeaa)DE-He213 Interleukin-2 (dpeaa)DE-He213 Renal cell carcinoma (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Survival (dpeaa)DE-He213 PROCLAIM (dpeaa)DE-He213 Daniels, Gregory A. aut McDermott, David F. aut Clark, Joseph I. aut Kaufman, Howard L. aut Logan, Theodore F. aut Singh, Jatinder aut Kaur, Meenu aut Luna, Theresa L. aut Gregory, Nancy aut Morse, Michael A. aut Wong, Michael K. K. aut Dutcher, Janice P. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 5(2017), 1 vom: 19. Dez. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:5 year:2017 number:1 day:19 month:12 https://dx.doi.org/10.1186/s40425-017-0307-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2017 1 19 12
allfieldsGer	10.1186/s40425-017-0307-5 doi (DE-627)SPR036436348 (SPR)s40425-017-0307-5-e DE-627 ger DE-627 rakwb eng Curti, Brendan verfasserin aut Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response. Immune-related adverse events (dpeaa)DE-He213 Interleukin-2 (dpeaa)DE-He213 Renal cell carcinoma (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Survival (dpeaa)DE-He213 PROCLAIM (dpeaa)DE-He213 Daniels, Gregory A. aut McDermott, David F. aut Clark, Joseph I. aut Kaufman, Howard L. aut Logan, Theodore F. aut Singh, Jatinder aut Kaur, Meenu aut Luna, Theresa L. aut Gregory, Nancy aut Morse, Michael A. aut Wong, Michael K. K. aut Dutcher, Janice P. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 5(2017), 1 vom: 19. Dez. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:5 year:2017 number:1 day:19 month:12 https://dx.doi.org/10.1186/s40425-017-0307-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2017 1 19 12
allfieldsSound	10.1186/s40425-017-0307-5 doi (DE-627)SPR036436348 (SPR)s40425-017-0307-5-e DE-627 ger DE-627 rakwb eng Curti, Brendan verfasserin aut Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry 2017 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s). 2017 Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response. Immune-related adverse events (dpeaa)DE-He213 Interleukin-2 (dpeaa)DE-He213 Renal cell carcinoma (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Survival (dpeaa)DE-He213 PROCLAIM (dpeaa)DE-He213 Daniels, Gregory A. aut McDermott, David F. aut Clark, Joseph I. aut Kaufman, Howard L. aut Logan, Theodore F. aut Singh, Jatinder aut Kaur, Meenu aut Luna, Theresa L. aut Gregory, Nancy aut Morse, Michael A. aut Wong, Michael K. K. aut Dutcher, Janice P. aut Enthalten in Journal for ImmunoTherapy of Cancer London : BioMed Central, 2013 5(2017), 1 vom: 19. Dez. (DE-627)750086335 (DE-600)2719863-7 2051-1426 nnns volume:5 year:2017 number:1 day:19 month:12 https://dx.doi.org/10.1186/s40425-017-0307-5 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER SSG-OLC-PHA GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 5 2017 1 19 12
language	English
source	Enthalten in Journal for ImmunoTherapy of Cancer 5(2017), 1 vom: 19. Dez. volume:5 year:2017 number:1 day:19 month:12
sourceStr	Enthalten in Journal for ImmunoTherapy of Cancer 5(2017), 1 vom: 19. Dez. volume:5 year:2017 number:1 day:19 month:12
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Immune-related adverse events Interleukin-2 Renal cell carcinoma Melanoma Survival PROCLAIM
isfreeaccess_bool	true
container_title	Journal for ImmunoTherapy of Cancer
authorswithroles_txt_mv	Curti, Brendan @@aut@@ Daniels, Gregory A. @@aut@@ McDermott, David F. @@aut@@ Clark, Joseph I. @@aut@@ Kaufman, Howard L. @@aut@@ Logan, Theodore F. @@aut@@ Singh, Jatinder @@aut@@ Kaur, Meenu @@aut@@ Luna, Theresa L. @@aut@@ Gregory, Nancy @@aut@@ Morse, Michael A. @@aut@@ Wong, Michael K. K. @@aut@@ Dutcher, Janice P. @@aut@@
publishDateDaySort_date	2017-12-19T00:00:00Z
hierarchy_top_id	750086335
id	SPR036436348
language_de	englisch
fullrecord	<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">SPR036436348</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230519192140.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">201007s2017 xx \|\|\|\|\|o 00\| \|\|eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1186/s40425-017-0307-5</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)SPR036436348</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(SPR)s40425-017-0307-5-e</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Curti, Brendan</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2017</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="500" ind1=" " ind2=" "><subfield code="a">© The Author(s). 2017</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. 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author	Curti, Brendan
spellingShingle	Curti, Brendan misc Immune-related adverse events misc Interleukin-2 misc Renal cell carcinoma misc Melanoma misc Survival misc PROCLAIM Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry
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topic_title	Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry Immune-related adverse events (dpeaa)DE-He213 Interleukin-2 (dpeaa)DE-He213 Renal cell carcinoma (dpeaa)DE-He213 Melanoma (dpeaa)DE-He213 Survival (dpeaa)DE-He213 PROCLAIM (dpeaa)DE-He213
topic	misc Immune-related adverse events misc Interleukin-2 misc Renal cell carcinoma misc Melanoma misc Survival misc PROCLAIM
topic_unstemmed	misc Immune-related adverse events misc Interleukin-2 misc Renal cell carcinoma misc Melanoma misc Survival misc PROCLAIM
topic_browse	misc Immune-related adverse events misc Interleukin-2 misc Renal cell carcinoma misc Melanoma misc Survival misc PROCLAIM
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title	Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry
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title_full	Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry
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author_browse	Curti, Brendan Daniels, Gregory A. McDermott, David F. Clark, Joseph I. Kaufman, Howard L. Logan, Theodore F. Singh, Jatinder Kaur, Meenu Luna, Theresa L. Gregory, Nancy Morse, Michael A. Wong, Michael K. K. Dutcher, Janice P.
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title_sort	improved survival and tumor control with interleukin-2 is associated with the development of immune-related adverse events: data from the $ proclaim^{sm} $ registry
title_auth	Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry
abstract	Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response. © The Author(s). 2017
abstractGer	Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response. © The Author(s). 2017
abstract_unstemmed	Background Immune related adverse events (irAEs) are associated with immunotherapy for cancer and while results suggest improvement in tumor control and overall survival in those experiencing irAEs, the long-term impact is debated. We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. IrAEs resulting from IL-2 and from CPIs are qualitatively different, and likely reflect different mechanisms of action of immune activation and response. © The Author(s). 2017
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title_short	Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry
url	https://dx.doi.org/10.1186/s40425-017-0307-5
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author2	Daniels, Gregory A. McDermott, David F. Clark, Joseph I. Kaufman, Howard L. Logan, Theodore F. Singh, Jatinder Kaur, Meenu Luna, Theresa L. Gregory, Nancy Morse, Michael A. Wong, Michael K. K. Dutcher, Janice P.
author2Str	Daniels, Gregory A. McDermott, David F. Clark, Joseph I. Kaufman, Howard L. Logan, Theodore F. Singh, Jatinder Kaur, Meenu Luna, Theresa L. Gregory, Nancy Morse, Michael A. Wong, Michael K. K. Dutcher, Janice P.
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We evaluated irAE reports related to high dose interleukin-2 therapy (IL-2) documented in the $ PROCLAIM^{SM} $ registry data base from 2008 to 2016 (NCT01415167, August 9, 2011). Methods Reports on 1535 patients, including 623 with metastatic melanoma (mM) and 919 with metastatic renal cell cancer (mRCC) (7 patients had both diseases), were queried for irAEs. The timing of the event was categorized as occurring before, during or after IL-2 or related to any checkpoint inhibitor (CPI). mM patients and mRCC patients were analyzed separately. Tumor control [complete + partial response + stable disease (CR + PR + SD) was compared between those experiencing no irAE versus those with the development of irAEs. Survival was analyzed by tumor type related to timing of irAE and IL-2, and in those with or without exposure to CPI. Results Median follow-up was 3.5+ years (range 1–8+ years), 152 irAEs were reported in 130 patients (8.4% of all $ PROCLAIM^{SM} $ patients): 99 (16%) in mM and 53 (5.8%) in mRCC patients. 31 irAEs occurred prior to IL-2, 24 during IL-2, and 97 after IL-2 therapy. 74 irAEs were attributed to IL-2 only (during/ after IL-2). Of the 97 post IL-2 irAEs, 24 were attributed to CPI, and 15 could not be distinguished as caused by IL-2 or CPI. Tumor control was 71% for those experiencing irAE, and 56% for those with no irAE (p = 0.0008). Overall survival was significantly greater for those experiencing irAEs during/ after IL-2 therapy, compared to those with no irAE or irAE before IL-2 therapy, in mM patients, median 48 months vs 18 months (p < 0.0001), and in mRCC patients, median 60 months vs 40 months (p = 0.0302), independent of CPI-related irAEs. IL-2-related irAEs were primarily vitiligo and thyroid dysfunction (70% of IL-2 related irAEs), with limited further impact. Conclusions irAEs following IL-2 therapy are associated with improved tumor control and overall survival. 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Improved survival and tumor control with Interleukin-2 is associated with the development of immune-related adverse events: data from the $ PROCLAIM^{SM} $ registry

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