In patients with sickle cell disease (SCD), assessing adhesion phenotypes using the flow adhesion of whole blood to p-selectin (FA-WB-PSel) biomarker enabled clinicians to identify biologic responders versus non-responders and monitor therapeutic efficacy in real-world settings. The study results were presented at the 66th American Society of Hematology Annual Meeting and Exposition.
“Specifically, this approach provides a validated means of assessing and tracking the response to U.S. Food and Drug Administration-approved anti-p-selectin therapy, such as crizanlizumab,” presenting author Jennell White, PhD, of Wayne State University and Functional Fluidics, Inc., both in Michigan, told ASH Clinical News. “This could improve personalized treatment strategies and enhance patient outcomes by aligning therapy choices with specific biologic phenotypes.”
Currently, patients with SCD are “prescribed crizanlizumab based on clinical presentations, such as historical vaso-occlusive crises frequency, and response is monitored solely by subjective reductions in pain crises. Our findings suggest a paradigm shift is needed,” Dr. White continued. “Clinicians should assess p-selectin phenotypes at baseline to better understand individual patient biology, consider the biologic phenotype when selecting disease-modifying therapies like crizanlizumab, and monitor biologic responses to therapy alongside clinical outcomes to provide a more comprehensive view of treatment efficacy. This evidence-based approach could lead to more precise, biologically informed treatment decisions.”
The retrospective study assessed the FA-WB-PSel biomarker in 994 patients with SCD from five U.S. clinics between 2018 and 2024 on or off crizanlizumab therapy. Researchers compared FA-WB-PSel levels in blood samples from treated and non-treated patients and individual patients who received at least three biomarker evaluations within one year pre- and post-treatment.
Of the 5,507 clinical samples, 1,160 were collected during treatment from 61 patients as reported by clinicians and 14 patients with confirmed treatment start dates, and 4,347 were collected during non-treatment. Non-treated samples showed higher adhesion than treated samples (56.4 to 51.7 cells/mm²; p=0.0001). The proportion of FA-WB-PSel levels above the critical threshold (50 cells/mm2) decreased from 42.9% to 39.5% (p=0.039) with treatment.
Similarly, crizanlizumab reduced the adhesive phenotype of whole blood samples obtained from 61 patients (1,014 treated and 1,159 non-treated; 61 to 52 cells/mm²; p=0.0071), along with critical biomarker levels (46.6% to 40.0%; p=0.0021) and the proportion of patients with severe pain, defined as a pain score of at least 7 on a 0-10 scale (92.2% to 85.7%; p=0.0000). Further, 36 of 61 patients showed FA-WB-Psel levels within the normal range (<50 cells/mm2). FA-WB-PSel levels and pain scores appeared unaffected by treatment. However, 25 patients with critical FA-WB-PSel levels showed decreases in adhesion (76 to 49 cells/mm²; p<0.05) with treatment.
“We were surprised to find that approximately 43% of individuals with SCD exhibit critically high p-selectin adhesion phenotypes. Prior to this study, there was no population-scale insight into the proportion of the sickle cell population affected by abnormal p-selectin adhesive phenotypes. This finding identifies a significant subset of the population at increased risk for p-selectin-mediated vaso-occlusive pathology, offering a new perspective on disease heterogeneity and potential risk stratification,” Dr. White noted.
For the 14 patients with provider-confirmed therapy start dates, reduced mean FA-WB-PSel levels occurred post-treatment (pre = 69.97, post = 45.93 cells/mm2; p=0.0494), and non-treated FA-WB-PSel levels “strongly correlated” with patient response to therapy (r=-0.7877; p=0.0013). Additionally, 10 patients exhibiting high p-selectin activity (>50 cells/mm2) in the pretreatment period were more responsive to crizanlizumab one-year post-treatment (pre = 89.35, post = 50.61 cells/mm2; p=0.001), and biomarker levels stabilized post-treatment (pre = 60.27, post = 34.19 cells/mm2; p=0.001). Patients with low p-selectin activity were unaffected.
“The study underscores the significant biologic heterogeneity in SCD and highlights the need for clinicians to incorporate biologic phenotyping into patient care,” Dr. White said. “Key takeaways are that baseline assessment of biologic phenotypes is critical to understanding disease presentation and selecting appropriate therapies; over-reliance on clinical manifestations alone may lead to suboptimal outcomes in the era of targeted therapies like crizanlizumab; and a combination of biologic and clinical assessments is essential for monitoring response to current and future targeted therapies.”
“This biologic-informed approach aligns patient care with the evolving landscape of precision medicine in SCD,” Dr. White concluded.
Any conflicts of interest declared by the authors can be found in the original abstract.
Reference
White JU, Gao X, Bellemare K, et al. Further validation of flow adhesion of whole blood to p-selectin (FA-WB-PSEL) to assess targeted p-selectin therapies in sickle cell disease (SCD). Abstract 3875. Presented at the 66th American Society of Hematology Annual Meeting and Exposition; December 9, 2024; San Diego, California.
