High serum LDH and liver metastases are the dominant predictors of primary cancer resistance to anti-PD(L)1 immunotherapy Journal Article

  

Authors:	Dercle, L.; Ammari, S.; Roblin, E.; Bigorgne, A.; Champiat, S.; Taihi, L.; Plaian, A.; Hans, S.; Lakiss, S.; Tselikas, L.; Rouanne, M.; Deutsch, E.; Schwartz, L. H.; Gönen, M.; Flynn, J.; Massard, C.; Soria, J. C.; Robert, C.; Marabelle, A.
Article Title:	High serum LDH and liver metastases are the dominant predictors of primary cancer resistance to anti-PD(L)1 immunotherapy
Abstract:	Aim: Anti-PD-(L)1 immunotherapies improve survival in multiple cancers but remain ineffective for most patients. We applied machine-learning algorithms and multivariate analyses on baseline medical data to estimate their relative impact on overall survival (OS) upon anti-PD-(L)1 monotherapies. Method: This prognostic/predictive study retrospectively analysed 33 baseline routine medical variables derived from computed tomography (CT) images, clinical and biological meta-data. 695 patients with a diagnosis of advanced cancer were treated in prospective clinical trials in a single tertiary cancer centre in 3 cohorts including systemic anti-PD-(L)1 (251, 235 patients) versus other systemic therapies (209 patients). A random forest model combined variables to identify the combination (signature) which best estimated OS in patients treated with immunotherapy. The performance for estimating OS [95%CI] was measured using Kaplan–Meier Analysis and Log–Rank test. Results: Elevated serum lactate dehydrogenase (LDHhi) and presence of liver metastases (LM+) were dominant and independent predictors of short OS in independent cohorts of melanoma and non-melanoma solid tumours. Overall, LDHhiLM+ patients treated with anti-PD-(L)1 monotherapy had a poorer outcome (median OS: 3.1[2.4–7.8] months]) compared to LDHlowLM-patients (median OS: 15.3[8.9-NA] months; P < 0.0001). The OS of LDHlowLM-patients treated with immunotherapy was 28.8[17.9-NA] months (vs 13.1[10.8–18.5], P = 0.02) in the overall population and 30.3[19.93-NA] months (vs 14.1[8.69-NA], P = 0.0013) in patients with melanoma. Conclusion: LDHhiLM+ status identifies patients who shall not benefit from anti-PD-(L)1 monotherapy. It could be used in clinical trials to stratify patients and eventually address this specific medical need. © 2022 Elsevier Ltd
Keywords:	survival; adult; cancer chemotherapy; controlled study; human tissue; primary tumor; major clinical study; overall survival; monotherapy; systemic therapy; bone metastasis; cancer radiotherapy; outcome assessment; lymph node metastasis; antineoplastic agent; c reactive protein; cancer immunotherapy; melanoma; computer assisted tomography; neutrophil count; breast cancer; image analysis; tumor volume; cohort analysis; lung cancer; retrospective study; cancer resistance; liver metastasis; lung metastasis; albumin; brain metastasis; lactate dehydrogenase; leukocyte count; transitional cell carcinoma; kidney metastasis; lactate dehydrogenase blood level; skin metastasis; lymphocyte count; fibrinogen; adrenal metastasis; programmed death 1 ligand 1; pleura metastasis; non small cell lung cancer; liver metastases; molecularly targeted therapy; bladder metastasis; pancreas metastasis; albumin blood level; thyroid metastasis; machine learning; immune checkpoint inhibitor; cancer prognosis; non melanoma skin cancer; human; male; female; article; random forest; solid malignant neoplasm; hyperprogression
Journal Title:	European Journal of Cancer
Volume:	177
ISSN:	0959-8049
Publisher:	Elsevier Inc.
Date Published:	2022-12-01
Start Page:	80
End Page:	93
Language:	English
DOI:	10.1016/j.ejca.2022.08.034
PROVIDER:	scopus
PUBMED:	36332438
DOI/URL:	https://www.scopus.com/inward/record.uri?eid=2-s2.0-85140982232&doi=10.1016%2fj.ejca.2022.08.034&partnerID=40&md5=4161ca2c7b4e4125d1d264afbc181806
Notes:	Article -- Export Date: 1 December 2022 -- Source: Scopus

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