Melissa A. Babcook MD, PhD, Gerard Lozanski, MD, Sarah A. Wall MD, MPH
Background
CD123 expression in MPNs has been reported in case series and targeted in one phase I study of patients with chronic phase MPN. We describe the clinical phenotype of patients with accelerated (AP) or blast phase (BP) MPNs paired with CD123 co-expression on CD45(dim) myeloid blasts.
Methods
Subjects were identified by diagnosis in the Ohio State University Comprehensive Cancer Center Leukemia Tissue Bank (OSUCCC-LTB). Clinical data were collected by retrospective chart review with IRB approval. CD123 expression was measured by immunophenotyping of cryopreserved peripheral blood (PB) or marrow (BM) samples. Blasts were identified by CD45(dim) gating and co-expression of CD7/13/33/34/117/123 was measured. CD123 expression was stratified by quartile and correlation with clinical characteristics measured by Chi-square test.
Results
41 PB or BM samples from 24 subjects were identified from the OSUCCC-LTB. Nine subjects had paired PB and BM specimens, 6 had samples obtained at multiple timepoints. Median age at sample collection was 65.8 years (range 35.2-79.7) and median time from diagnosis was 13.1 months (range 0-96.5). Constitutional symptoms were present at collection for 24 samples (58.5%) and splenomegaly present for 20 samples (51.3%). At sample collection, 19.5% had never received treatment, 19.5% had been previously treated, and 61% were currently on treatment, most (n=16, 64%) with JAK inhibitor. 19 samples were obtained in chronic phase (46.3%), 9 in AP (22.0%), and 13 in BP (31.7%). 16 samples (39.0%) were from transfusion-dependent patients, most (68.8%) for both red blood cell and platelets. Median PB blasts were 3.2% (range:0-76) and BM blasts were 3% (range 0-82) by morphology. Molecular sequencing and karyotype were available for 18 (43.9%) and 27 (65.9%), respectively. The most common mutations identified were JAK2 (50%), ASXL1 (27.8%), SRSF2 (22.2%), CALR (16.7%), and TP53 (16.7%). Normal karyotype was found in 37%, 33.3% had complex karyotype, 11.1% had del 5q or 7q/-7, and 18.5% had del 13q or 20q. CD123 expression on the CD45-gated blasts ranged from 0.3-95.6% with a median value of 11.02%. CD123 expression is shown in figure 1. Figure 2a shows correlation between CD123 expression and disease phase (p < 0.01). Figure 2b shows CD123 expression correlation with ASXL1 mutation status (p =0.023). There were no statistically significant associations between CD123 expression and any other tested variables.
Conclusions
These data support a clinical trial targeting CD123 in high risk MPNs, defined by blasts >10% or the presence of ASXL1 mutation, an important subpopulation of patients in need of more effective and less toxic therapy than current standards of care that typically include cytotoxic chemotherapy.