Risk and Outcomes of Second Malignancies in Patients With Philadelphia Chromosome–Negative Myeloproliferative Neoplasm: A SEER Database Analysis

PURPOSE Patients with myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF), have an increased incidence of second malignancies. This study describes the patterns, risk factors, and outcomes of second malignancies in MPN with the aim of refining our knowledge. METHODS Using SEER database (2000-2021), we identified patients diagnosed with MPNs. The incidence, patterns, and risk factors of second malignancies including synchronous neoplasms (SYNs, within 6 months of MPN diagnosis), second primary malignancies (SPMs, after 6 months), and secondary AML (s-AML) were assessed separately. Standardized incidence ratios (SIRs) assessed the risk of SPM and s-AML in the MPN cohort compared with the general population. RESULTS Among 43,930 patients with MPN, 1.6% developed SYN, 9.1% SPM, and 1.5% s-AML. Lung, prostate, breast, and colorectal cancers were most frequent solid SPMs, with lung cancer risk particularly higher in PV (SIR, 1.47) and ET (SIR, 1.23). Older age at MPN diagnosis (age 40-59 years, odds ratio [OR; 95% CI], 3.82 [3.09 to 4.78]; age 60-84 years, OR [95% CI], 6.19 [5.02 to 7.7]; ref: 18-39 years) and male sex ( v female, OR [95% CI], 1.37 [1.28 to 1.46]) were associated with a higher risk of SPM. The overall SPM risk was higher than that of the general population (SIR [95% CI], 1.14 [1.11 to 1.18]; P < .05), with a particularly higher risk of hematologic SPMs (SIR [95% CI], 1.70 [1.55 to 1.85]; P < .05) and s-AML (SIR [95% CI], 19.36 [17.92 to 20.88]; P < .05). SPM development was associated with reduced median survival (125 v 184 months, P < .0001) after MPN diagnosis. s-AML progression reduced the median survival to 80, 82, and 43 months for patients with PV, ET, and PMF, respectively. CONCLUSION Patients with MPN have a higher risk of second malignancies, compared with the general population, which is associated with reduced survival. This necessitates age-appropriate cancer screening, dermatologic examinations, and long-term surveillance. Further studies are warranted to delineate the underlying factors contributing to this risk.