Prognostic biomarkers for immunotherapy with ipilimumab in metastatic melanoma

Abstract

Summary New therapies, including the anti‐cytotoxic T lymphocyte antigen (CTLA)‐4 antibody, ipilimumab, is approved for metastatic melanoma. Prognostic biomarkers need to be identified, because the treatment has serious side effects. Serum samples were obtained before and during treatment from 56 patients with metastatic or unresectable malignant melanoma, receiving treatment with ipilimumab in a national Phase IV study (NCT0268196). Expression of a panel of 17 inflammatory‐related markers reflecting different pathways including extracellular matrix remodeling and fibrosis, vascular inflammation and monocyte/macrophage activation were measured at baseline and the second and/or third course of treatment with ipilimumab. Six candidate proteins [endostatin, osteoprotegerin (OPG), C‐reactive protein (CRP), pulmonary and activation‐regulated chemokine (PARC), growth differentiation factor 15 (GDF15) and galectin‐3 binding‐protein (Gal3BP)] were persistently higher in non‐survivors. In particular, high Gal3BP and endostatin levels were also independently associated with poor 2‐year survival after adjusting for lactate dehydrogenase, M‐stage and number of organs affected. A 1 standard deviation increase in endostatin gave 1·74 times [95% confidence interval (CI) = 1·10–2·78, P = 0·019] and for Gal3BP 1·52 times (95% CI = 1·01–2·29, P = 0·047) higher risk of death in the adjusted model. Endostatin and Gal3BP may represent prognostic biomarkers for patients on ipilimumab treatment in metastatic melanoma and should be further evaluated. Owing to the non‐placebo design, we could only relate our findings to prognosis during ipilimumab treatment.

The Tumor and Host Immune Signature, and the Gut Microbiota as Predictive Biomarkers for Immune Checkpoint Inhibitor Response in Melanoma Patients

“…Simeone et al [ 68 ] reported the association of a decreased CRP level with disease stabilization and survival during 12 weeks of ipilimumab treatment in melanoma patients. These results have confirmation in the work of Nyakas et al [ 69 ], showing that increased CRP levels at several time points (baseline, week 4, and week 7) were observed in non-responders for ipilimumab therapy. Elevated pre-treatment CRP level was also shown to be related to poor OS in both anti-PD-1 and anti-CTLA-4 melanoma therapies [ 69 , 70 ].…”

Lectin affinity chromatography and quantitative proteomic analysis reveal that galectin-3 is associated with metastasis in nasopharyngeal carcinoma

“…The released Galectin-3 can bind to components of extracellular matrix and its membrane counterparts of other cells, which have in a wide range of biological events including cellular homeostasis, immune function, angiogenesis, tumor invasion and metastasis 25 . Galectin-3 has been reported as a diagnostic or prognostic marker linked to metastasis in many types of cancer such as thyroid 26,27 , breast cancer 28 , melanoma 29 , lung cancer 30 , sarcoma 31 , gastric cancer 32 , prostate cancer 33 and oral tongue cancer 34 . Here, we showed that Galectin-3 was greatly expressed in highly metastatic NPC cells compared to lowly metastatic cells.…”

In-depth plasma proteomics reveals increase in circulating PD-1 during anti-PD-1 immunotherapy in patients with metastatic cutaneous melanoma

“…11 21 Altogether, some of these findings coincide with previous reports on the involvement of immunological proteins in antitumor response to CM. [22][23][24][25][26][27][28] Protein plasma levels can predict PFs To detect potential predictive biomarkers, we also analyzed the association between pre-trm plasma protein levels and PFS. No clinical variables were associated with PFS in the HiRIEF LC-MS/MS-analyzed subgroup of anti-PD-1 treatment cohort (n=13); therefore we performed univariate analyses, which showed associations between protein pre-trm plasma levels of 109 proteins and PFS in this cohort (p<0.05, no FDR; online supplementary table S8, additional file 2).…”