Combined immunotherapy improves outcome for replication repair deficient (RRD) high-grade glioma failing anti-PD1 monotherapy: A report from the International RRD Consortium
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00064203%3A_____%2F24%3A10470169" target="_blank" >RIV/00064203:_____/24:10470169 - isvavai.cz</a>
Alternative codes found
RIV/00216208:11130/24:10470169
Result on the web
<a href="https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=249z.hPdUl" target="_blank" >https://verso.is.cuni.cz/pub/verso.fpl?fname=obd_publikace_handle&handle=249z.hPdUl</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1158/2159-8290.CD-23-0559" target="_blank" >10.1158/2159-8290.CD-23-0559</a>
Alternative languages
Result language
angličtina
Original language name
Combined immunotherapy improves outcome for replication repair deficient (RRD) high-grade glioma failing anti-PD1 monotherapy: A report from the International RRD Consortium
Original language description
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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30102 - Immunology
Result continuities
Project
—
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2024
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Cancer Discovery
ISSN
2159-8290
e-ISSN
2159-8290
Volume of the periodical
14
Issue of the periodical within the volume
2
Country of publishing house
ES - SPAIN
Number of pages
16
Pages from-to
258-273
UT code for WoS article
001159208100013
EID of the result in the Scopus database
2-s2.0-85184656237