Combined immunotherapy improves outcome for replication repair deficient (RRD) high-grade glioma failing anti-PD1 monotherapy: A report from the International RRD Consortium.

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Fältnamn	Indikatorer	Metadata
000		05194naa a2201033 4500
001		oai:gup.ub.gu.se/330985
003		SwePub
008		240604s2024 \| \|\|\|\|\|\|\|\|\|\|\|000 \|\|eng\|
024	7	a https://gup.ub.gu.se/publication/3309852 URI
024	7	a https://doi.org/10.1158/2159-8290.CD-23-05592 DOI
040		a (SwePub)gu
041		a eng
042		9 SwePub
072	7	a ref2 swepub-contenttype
072	7	a art2 swepub-publicationtype
100	1	a Das, Anirban4 aut
245	1 0	a Combined immunotherapy improves outcome for replication repair deficient (RRD) high-grade glioma failing anti-PD1 monotherapy: A report from the International RRD Consortium.
264	1	c 2024
520		a Immune-checkpoint inhibition (ICI) is effective for replication-repair deficient, high-grade gliomas (RRD-HGG). Clinical/biologic impact of immune-directed approaches after failing ICI-monotherapy are unknown. We performed an international study on 75 patients treated with anti-PD1; 20 are progression-free (median follow-up: 3.7-years). After 2nd-progression/recurrence (n=55), continuing ICI-based salvage prolonged survival to 11.6-months (n=38; p<0.001), particularly for those with extreme mutation burden (p=0.03). Delayed, sustained responses were observed, associated with changes in mutational spectra and immune-microenvironment. Response to re-irradiation was explained by an absence of deleterious post-radiation indel signatures (ID8). Increased CTLA4-expression over time, and subsequent CTLA4-inhibition resulted in response/stable disease in 75%. RAS-MAPK-pathway inhibition led to reinvigoration of peripheral immune and radiological responses. Local (flare) and systemic immune adverse events were frequent (biallelic mismatch-repair deficiency > Lynch syndrome). We provide mechanistic rationale for the sustained benefit in RRD-HGG from immune-directed/ synergistic salvage therapies. Future approaches need to be tailored to patient and tumor biology.
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Pediatrik0 (SwePub)302212 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Pediatrics0 (SwePub)302212 hsv//eng
650	7	a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe
650	7	a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng
700	1	a Fernandez, Nicholas R4 aut
700	1	a Levine, Adrian4 aut
700	1	a Bianchi, Vanessa4 aut
700	1	a Stengs, Lucie K4 aut
700	1	a Chung, Jiil4 aut
700	1	a Negm, Logine4 aut
700	1	a Dimayacyac, Jose Rafael4 aut
700	1	a Chang, Yuan4 aut
700	1	a Nobre, Liana4 aut
700	1	a Ercan, Ayse B4 aut
700	1	a Sanchez-Ramirez, Santiago4 aut
700	1	a Sudhaman, Sumedha4 aut
700	1	a Edwards, Melissa4 aut
700	1	a Larouche, Valerie4 aut
700	1	a Samuel, David4 aut
700	1	a Van Damme, An4 aut
700	1	a Gass, David4 aut
700	1	a Ziegler, David S4 aut
700	1	a Bielack, Stefan S4 aut
700	1	a Koschmann, Carl4 aut
700	1	a Zelcer, Shayna4 aut
700	1	a Yalon-Oren, Michal4 aut
700	1	a Campino, Gadi Abede4 aut
700	1	a Sarosiek, Tomasz4 aut
700	1	a Nichols, Kim E4 aut
700	1	a Loret De Mola, Rebecca4 aut
700	1	a Bielamowicz, Kevin4 aut
700	1	a Sabel, Magnus,d 1966u Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för pediatrik,Institute of Clinical Sciences, Department of Pediatrics4 aut0 (Swepub:gu)xsabma
700	1	a Frojd, Charlotta A4 aut
700	1	a Wood, Matthew D4 aut
700	1	a Glover, Jason M4 aut
700	1	a Lee, Yi-Yen4 aut
700	1	a Vanan, Magimairajan4 aut
700	1	a Adamski, Jenny K4 aut
700	1	a Perreault, Sebastien4 aut
700	1	a Chamdine, Omar4 aut
700	1	a Hjort, Magnus Aasved4 aut
700	1	a Zapotocky, Michal4 aut
700	1	a Carceller, Fernando4 aut
700	1	a Wright, Erin4 aut
700	1	a Fedorakova, Ivana4 aut
700	1	a Lossos, Alexander4 aut
700	1	a Tanaka, Ryuma4 aut
700	1	a Osborn, Michael4 aut
700	1	a Blumenthal, Deborah T4 aut
700	1	a Aronson, Melyssa4 aut
700	1	a Bartels, Ute4 aut
700	1	a Huang, Annie4 aut
700	1	a Ramaswamy, Vijay4 aut
700	1	a Malkin, David4 aut
700	1	a Shlien, Adam4 aut
700	1	a Villani, Anita4 aut
700	1	a Dirks, Peter B4 aut
700	1	a Pugh, Trevor J4 aut
700	1	a Getz, Gad4 aut
700	1	a Maruvka, Yosef E4 aut
700	1	a Tsang, Derek S4 aut
700	1	a Ertl-Wagner, Birgit4 aut
700	1	a Hawkins, Cynthia4 aut
700	1	a Bouffet, Eric4 aut
700	1	a Morgenstern, Daniel A4 aut
700	1	a Tabori, Uri4 aut
710	2	a Göteborgs universitetb Institutionen för kliniska vetenskaper, Avdelningen för pediatrik4 org
773	0	t Cancer discoveryg 14:2, s. 258-273q 14:2<258-273x 2159-8290
856	4 8	u https://gup.ub.gu.se/publication/330985
856	4 8	u https://doi.org/10.1158/2159-8290.CD-23-0559

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Av författaren/redakt...: Das, Anirban; Fernandez, Nicho ...; Levine, Adrian; Bianchi, Vanessa; Stengs, Lucie K; Chung, Jiil; visa fler...; Negm, Logine; Dimayacyac, Jose ...; Chang, Yuan; Nobre, Liana; Ercan, Ayse B; Sanchez-Ramirez, ...; Sudhaman, Sumedh ...; Edwards, Melissa; Larouche, Valeri ...; Samuel, David; Van Damme, An; Gass, David; Ziegler, David S; Bielack, Stefan ...; Koschmann, Carl; Zelcer, Shayna; Yalon-Oren, Mich ...; Campino, Gadi Ab ...; Sarosiek, Tomasz; Nichols, Kim E; Loret De Mola, R ...; Bielamowicz, Kev ...; Sabel, Magnus, 1 ...; Frojd, Charlotta ...; Wood, Matthew D; Glover, Jason M; Lee, Yi-Yen; Vanan, Magimaira ...; Adamski, Jenny K; Perreault, Sebas ...; Chamdine, Omar; Hjort, Magnus Aa ...; Zapotocky, Micha ...; Carceller, Ferna ...; Wright, Erin; Fedorakova, Ivan ...; Lossos, Alexande ...; Tanaka, Ryuma; Osborn, Michael; Blumenthal, Debo ...; Aronson, Melyssa; Bartels, Ute; Huang, Annie; Ramaswamy, Vijay; Malkin, David; Shlien, Adam; Villani, Anita; Dirks, Peter B; Pugh, Trevor J; Getz, Gad; Maruvka, Yosef E; Tsang, Derek S; Ertl-Wagner, Bir ...; Hawkins, Cynthia; Bouffet, Eric; Morgenstern, Dan ...; Tabori, Uri; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Pediatrik

MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Cancer och onkol ...

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