Researchers Develop Predictive Model for Patients with Prefibrotic Primary Myelofibrosis

Researchers from multiple institutions in China developed a model to predict the probability of overt primary myelofibrosis (PMF)-free survival at 3, 5, and 10 years in patients with prefibrotic primary myelofibrosis (pre-PMF). The nomogram model demonstrated favorable predictive capabilities and clinical value, based on results published in The Lancet. The tool may pave the way to improved screening, enabling the identification of patients in need of appropriate monitoring and counseling.¹

Early intervention at the precursor stage is crucial for ensuring optimal outcomes for patients. Image Credit: © atipong - stock.adobe.com

PMF is a rare, fatal myeloproliferative neoplasm resulting in the overproduction of hematopoietic stem cells, which interferes with healthy red blood cell production. In 2016, the WHO created 2 classifications for the disease: pre-PMF, a precursor of PMF, and overt PMF. In pre-PMF, patients typically do not experience all the symptoms associated with overt PMF, which can mimic other similar diseases such as essential thrombocytopenia and make it difficult to properly diagnose.^2-4

Following diagnosis, patients can be grouped based on risk—low-risk, intermediate-risk, and high-risk. Patients in the intermediate- and high-risk groups have an increased chance of progressing to overt PMF and may require more extensive treatment options, such as stem cell transplantation. Patients with pre-PMF have a 15.2% risk of progressing to overt PMF and a 4.7% risk of developing acute myeloid leukemia.^4,5

To create the model, the researchers reevaluated 2275 patients with myeloproliferative neoplasm across 19 hematology centers from January 2010 to May 2024, as well as 338 eligible patients with pre-PMF who were reclassified and included in the study. The participant with pre-PMF were randomly assigned to be in either a training cohort (212 patients) or a validation cohort (126 patients). Risk factors idenfitied using LASSO and Cox analyses were used to construct the model. To assess the performance of the nomogram, the researchers used receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).¹

The LASSO and Cox analyses found that male sex, MF-1, platelet count, lactate dehydrogenase, and peripheral blood blasts as independent risk factors for the progression to overt PMF in pre-PMF patients. The researchers’ ROC analysis identified that the area under the curve (AUC) values of 0.812 at 3 years, 0.854 at 5 years, and 0.750 at 10 years in the training cohort. The validation cohort had AUC values of 0.910, 0.881, and 0.825, respectively.¹

DCA results showed the model had good predictive ability for pre-PMF progression, as well as good clinical application value. The probability of overt-PMF-free survival significantly differed among the low-risk (≤152), intermediate-risk (>152 and ≤209) and high-risk (>209) groups.¹

Patients with overt PMF face significant challenges and their disease can not only disrupt quality of life— it is often fatal. Early intervention at the precursor stage is crucial for ensuring optimal outcomes for patients.

REFERENCES

1. Hu S, Yang X, Zhu X, et al. A predictive model for progression to overt primary myelofibrosis in prefibrotic primary myelofibrosis patients. The Lancet. October 14, 2024. doi:10.2139/ssrn.4983769

2. Study finds ruxolitinib may slow fibrosis progression in myelofibrosis. Pharmacy Times. September 24, 2024. Accessed November 8, 2024. https://www.pharmacytimes.com/view/study-finds-ruxolitinib-may-slow-fibrosis-progression-in-myelofibrosis

3. Finazzi G, Vannucchi A, Barbui T. Prefibrotic myelofibrosis: treatment algorithm 2018. Blood Cancer Journal. November 7, 2018. doi:10.1038/s41408-018-0142-z

4. What is prefibrotic myelofibrosis. Healthtree. March 19, 2024. Accessed November 8, 2024. https://healthtree.org/myelofibrosis/community/articles/what-is-prefibrotic-myelofibrosis#:~:text=Pre%2DPMF%20is%20an%20earlier,where%20blood%20cells%20are%20produced

5. Baumeister J, Chatain N, Sofias AM, et al. Progression of myeloproliferative neoplasms (mpn): diagnostic and therapeutic perspectives. Cells. 2021 December 16, 2021. doi: 10.3390/cells10123551