Assessing Hyperferritinemia as Predictive Biomarker in CMML

Chronic myelomonocytic leukemia (CMML) is a heterogenous blood cancer which exhibits features similar to myeloproliferative neoplasms (MPN), and myelodysplastic syndromes (MDS). Follwing growing evidence of a link between systemic inflammation and myeloid cancers, researchers sought to elucidate this link in CMML, given its association with inflammation and end-organ damage. The research team, led by Luis E. Aguirre and colleagues, hypothesized that high ferritin levels may serve as a viable biomarker of disease activity, thereby discerning which patients are at an elevated risk of poor outcomes. They conducted an analysis that was presented at the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting.

This retrospective study consisted of 729 patients with CMML (median age at diagnosis, 71) who were treated at Moffitt Cancer Center between August 1995 and October 2020. The population of interest were stratified in two cohorts based on ferritin levels (<1000 or ≥1000 ng/mL). Hyperferritinemia was defined in this study as ferritin >1000, either at time of diagnosis or during follow-up. Overall, 571 patients were analyzed with available ferritin levels.

The results showed that 29% of patients with CMML developed hyperferritinemia, while 71% did not. The researchers noted that patients with higher ferritin levels tended to present with CMML-2 (p = 0.001) and harbor a proliferative phenotype (p = 0.01). Moreover, the analysis showed that hyperferritinemia was correlated with more profound fibrosis (p = 0.007), cytopenias (p <0.05), % peripheral blasts (p <0.05), RBC and PLT transfusion dependence (p <0.05). The investigators observed that hyperferritinemia patients had higher risk disease per IPSS-R, CPSS and all CMML models (p <0.05); as well as higher rates of AML transformation (p <0.05) and were also more likely to require earlier treatment (within 3 years of diagnosis).

The researchers concluded that their findings “indicate that hyperferritinemia is an independent prognostic biomarker that may serve as a surrogate representative of disease biology and comorbidities in CMML.”