Abstract
We conducted a large international nested case-control study including 1881 patients with Philadelphia-negative myeloproliferative neoplasms (MPN). Cases (n = 647) were patients with second cancer (SC: carcinoma, non-melanoma skin cancer, hematological second cancer, and melanoma) and controls (n = 1234) were patients without SC, matched with cases for sex, age at MPN diagnosis, date of MPN diagnosis, and MPN disease duration. The aim was to evaluate the risk of SC after exposure to cytoreductive drugs. Patients exposed to hydroxyurea (HU) (median: 3 years) had a risk of SC similar to unexposed patients (OR = 1.06, 95% CI 0.82–1.38). In contrast, in cancer-specific stratified multivariable analysis, HU had two-fold higher risk of non-melanoma (NM) skin cancer (OR = 2.28, 95% CI 1.15–4.51). A significantly higher risk of NM-skin cancer was also documented for pipobroman (OR = 3.74, 95% CI 1.00–14.01), ruxolitinib (OR = 3.87, 95% CI 1.18–12.75), and for drug combination (OR = 3.47, 95% CI 1.55–7.75). These three drugs did not show excess risk of carcinoma and hematological second cancer compared with unexposed patients. Exposure to interferon, busulfan, and anagrelide did not increase the risk. In summary, while it is reassuring that no excess of carcinoma was documented, a careful dermatologic active surveillance before and during the course of treatments is recommended.
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Acknowledgements
This study was supported by the FROM Research Foundation, Papa Giovanni XXIII Hospital, Bergamo, Italy. The study was also supported by Associazione Italiana per la Ricerca sul Cancro, grant 5perMille, progetto MYNERVA, to PG and AMV.
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TB designed the study, collected the data, interpreted the results and wrote the paper. AG collected the data, performed the statistical analysis and wrote the paper. AMV, VDS, GF, and MM interpreted the results and wrote the paper. The final version of the manuscript was approved by all the other authors.
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TB has been a speaker and consultant for Novartis and he has received research grant from AOP Orphan. VDS has received consulting and lecture fees from Amgen, Celgene, Novartis, and institutional research grants from Bayer and Novartis. MLF has been a member of advisory Board for Novartis and she has received travel grants from the company. MFM has been a speaker and consultant for Novartis. MM has received honoraria for advisory boards and lectures at sponsored meetings from Celgene, Amgen, Janssen, Gilead, Novartis. AMV has been a speaker for Novartis, Celgene, and Shire and participated to advisory boards of Celgene, Incyte, Novartis. The remaining authors declare that they have no conflict of interest.
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Barbui, T., Ghirardi, A., Masciulli, A. et al. Second cancer in Philadelphia negative myeloproliferative neoplasms (MPN-K). A nested case-control study. Leukemia 33, 1996–2005 (2019). https://doi.org/10.1038/s41375-019-0487-8
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DOI: https://doi.org/10.1038/s41375-019-0487-8
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