Current Definitions and Clinical Implications of Biomarkers in Graft-versus-Host Disease.

Hematopoietic cell transplantation (HCT) is a potentially curative treatment for many hematologic and nonhematologic disorders. Graft-versus-host-disease (GVHD) in its acute or chronic form remains the most important nonrelapse post-HCT complication. Biomarkers offer objective, unbiased information on systemic disorders, and significant attention has focused on identifying biomarkers for GVHD. Ideally, a GVHD biomarker is actionable, with the results of biomarker testing used to guide clinical management of disease and clinical trial design. Although many GVHD biomarkers have been identified, none have been properly qualified for clinical use. The National Institutes of Health (NIH) and Food and Drug Administration (FDA) have provided biomarker subtype definitions; however, confusion remains about the proper definition and application of these subtypes in the HCT field. The 2014 NIH consensus development project provided a framework for the development of biomarkers for clinical practice. This review aims to clarify the biomarker subtype definitions and reemphasize the developmental framework. Armed with this knowledge, clinicians can properly translate GVHD biomarkers for clinical use.

Regenerating islet-derived protein 3-α is a prognostic biomarker for gastrointestinal chronic graft-versus-host disease.

Prognostic biomarkers used to identify likelihood of disease progression have not been identified for chronic graft-versus-host disease (cGVHD), the leading cause of late nonrelapse mortality (NRM) in survivors of allogeneic hematopoietic cell transplantation. Gastrointestinal cGVHD (GI-cGVHD) has been particularly challenging to classify. Here, we analyzed 3 proteomics markers (Regenerating islet-derived protein 3-α [Reg3α], C-X-C motif ligand 9 [CXCL9], and Stimulation-2 [ST2]) in 2 independent cohorts of patients with cGVHD totaling 289 patients. Plasma concentrations of Reg3α were significantly increased in patients with GI-cGVHD (P = .0012) compared with those without (P = .01), but plasma concentrations of CXCL9 and ST2 were not. Patients with high Reg3α (≥72 ng/mL) vs low Reg3α had higher NRM (23% vs 11%; P = .015). Because Reg3α has been identified as a lower GI tract marker in acute GVHD, we correlated Reg3α with lower acute-like GI-cGVHD vs classical fibrotic-like esophageal manifestations and found that Reg3α did not differ between the subtypes. No difference was observed between upper GI tract and lower GI tract subtypes. Patients with extremely high Reg3α (≥180 ng/mL) had higher GI scores but not higher scores for the lower GI tract. In a multivariable Cox regression model, patients with high Reg3α were 1.9 times more likely to die without relapse. Our findings demonstrate the utility of Reg3α as a prognostic marker for GI-cGVHD. These data warrant prospective biomarker validation studies.

An overview of multiplexed analyses of CAR T-cell therapies: insights and potential.

INTRODUCTION: Cancer immunotherapy is a rapidly growing field with exponential advancement in engineered immune cell-based therapies. For instance, an engineered chimeric antigen receptor (CAR) can be introduced in T-cells or other immune cells and adoptively transferred to target and kill cancer cells in hematologic malignancies or solid tumors. The first CAR-T-cell (CAR-T) therapy has been developed against CD19, a B-cell marker expressed on lymphoma and lymphoblastic leukemia. To allow for personalized treatment, proteomics approaches could provide insights into biomarkers for CAR-T therapy efficacy and toxicity. AREAS COVERED: We researched the most recent technology methods of biomarker evaluation used in the laboratory and clinical setting. Publications of CAR-T biomarkers were then systematically reviewed to provide a narrative of the most validated biomarkers of CAR-T efficacy and toxicity. Examples of biomarkers include CAR-T functionality and phenotype as well as interleukin-6 and other cytokines. EXPERT COMMENTARY: Biomarkers of CAR-T efficacy and toxicity have been identified, but still need to be validated and standardized across institutions. Moreover, few are used in the clinical setting due to limitations in real-time technology. Expansion of biomarker research could provide better understanding of patient response and risk of life-threatening side effects with potential for improved precision medicine.