Prolonged risk of specific malignancies following cyclophosphamide therapy among patients with granulomatosis with polyangiitis

• Published in: Rheumatology (Oxford, England) England), 2015-08, Vol.54 (8), p.1345-1350
• Main Authors: Faurschou, Mikkel, Mellemkjaer, Lene, Voss, Anne, Keller, Kresten Krarup, Hansen, Ib Tonder, Baslund, Bo
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antirheumatic Agents - adverse effects; Antirheumatic Agents - therapeutic use; Cohort Studies; Cyclophosphamide - adverse effects; Cyclophosphamide - therapeutic use; Denmark; Dose-Response Relationship, Drug; Female; Follow-Up Studies; Granulomatosis with Polyangiitis - drug therapy; Humans; Incidence; Male; Middle Aged; Registries; Retrospective Studies; Risk Factors; Skin Neoplasms - epidemiology; Treatment Outcome; Urinary Bladder Neoplasms - epidemiology; Young Adult
• ISSN: 1462-0324; 1462-0332
• DOI: 10.1093/rheumatology/keu372

The long-term cancer risk for patients treated for granulomatosis with polyangiitis (GPA) is not well characterized. We assessed the risk of early and late-occurring cancers among 293 patients diagnosed with GPA from 1973 to 1999 and followed throughout 2010. Cancer incidence in the cohort was determined by linkage with the Danish Cancer Registry and compared with that in the general population by calculation of standardized incidence ratios (SIRs). The median duration of follow-up was 9.7 years (range 0-36). Seventy-three cancers occurred, of which 30 were non-melanoma skin cancers (NMSCs) and 11 were bladder carcinomas. A high occurrence of NMSC was observed from the second year of follow-up onwards, with a SIR of 7.0 (95% CI 2.3, 16) for cases diagnosed ≥20 years after GPA. The incidence of bladder cancer increased after 5-9, 10-14 and 15-19 years of follow-up, with SIR estimates for these latency periods of 5.3 (95% CI 1.1, 15), 14.4 (95% CI 5.3, 31) and 10.5 (95% CI 1.2, 38), respectively. The incidence of myeloid leukaemia was significantly increased during years 5-9 [SIR 23.9 (95% CI 2.7, 86)]. Increased incidence of NMSC, bladder cancer and myeloid leukaemia was observed among patients exposed to cumulative CYC doses >36 g, while the only malignancy type observed in excess among those treated with lower CYC doses was NMSC. The cancer risk among CYC-naive patients was not significantly increased. GPA patients experience a greater than expected number of specific malignancies following conventional therapies. Our analyses demonstrate a substantially increased risk of very late-occurring NMSC and bladder cancer in this patient group.