Antibodies and chimeric antigen receptor-engineered T cells (CAR-T) are increasingly used for cancer immunotherapy. Small molecule inhibitors targeting cellular oncoproteins and enzymes such as BCR-ABL, JAK2, Bruton tyrosine kinase, FLT3, BCL-2, IDH1, IDH2, are biomarker-driven chemotherapy-free agents approved for several major hematological malignancies. LOXO-305, asciminib, “off-the-shelf” universal CAR-T cells and BCMA-directed immunotherapeutics as well as data from clinical trials on many novel agents and regimens were updated at the 2020 American Society of Hematology (ASH) Annual Meeting. Major developments and updates for the therapy of hematological malignancies were delineated at the recent Winter Symposium and New York Oncology Forum from the Chinese American Hematologist and Oncologist Network (CAHON.org). This study summarized the latest updates on novel agents and regimens for hematological malignancies from the 2020 ASH annual meeting.
Background
Immune checkpoint inhibitors have revolutionized cancer therapeutic paradigm and substantially improved the survival of patients with advanced malignancies. However, a significant limitation is the wide variability in clinical response.
Main text
Several biomarkers have been evaluated in prior and ongoing clinical trials to investigate their prognostic and predictive role of patient response, nonetheless, most have not been comprehensively incorporated into clinical practice. We reviewed published data regarding biomarkers that have been approved by the United States Food and Drug Administration as well as experimental tissue and peripheral blood biomarkers currently under investigation. We further discuss the role of current biomarkers to predict response and response to immune checkpoint inhibitors and the promise of combination biomarker strategies. Finally, we discuss ideal biomarker characteristics, and novel platforms for clinical trial design including enrichment and stratification strategies, all of which are exciting and dynamic to advance the field of precision immuno-oncology.
Conclusion
Incorporation and standardization of strategies to guide selection of combination biomarker approaches will facilitate expansion of the clinical benefit of immune checkpoint inhibitor therapy to appropriate subsets of cancer patients.
Liver Graft-versus-host disease (GVHD) is common in patients with post-transplant liver dysfunction following allogeneic hematopoietic stem cell transplantation (AHSCT). Oftentimes, the diagnosis is made clinically, and liver biopsy is deferred.Our objective was to evaluate the risk factors and clinical outcomes of liver GVHD among patients who developed post-transplant liver dysfunction. Additionally, we evaluated the feasibility of liver biopsy in this population. We compared outcomes between liver GVHD and a "non-liver GVHD" group, which consisted of other etiologies of post-transplant liver dysfunction. Between January 2003 and December 2010, 249 patients developed post-transplant liver dysfunction following AHSCT: 124 patients developed liver GVHD and 125 were in the "non-liver GVHD" group.The incidence of acute and chronic liver GVHD at one year was 15.7% and 31.0%, respectively. The competing risk analysis revealed full intensity conditioning regimen (Hazard ratio [HR], 1.76; P = .008) and related donor (HR, 1.68; P = .004) as independent risk factors for liver GVHD. The time-varying covariate Cox regression analysis with competing risk event, demonstrated that liver GVHD was independently associated with higher non-relapse mortality, and adverse relapse-free and overall survival. A total of 112 liver biopsies were performed in 100 patients. No major complications were observed. Liver biopsy confirmed prebiopsy hypotheses in 49% of cases, and led to treatment modification in 49% of patients. Our study shows that liver GVHD is associated with adverse survival. Liver biopsy is safe and often helps directing care in this setting.
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