1. Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma
- Author
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Geurts, Y.M, Neppelenbroek, S.I.M., Aleman, B.M.P., Janus, C.P., Krol, A.D., Spronsen, D.J. van, Plattel, W.J., Roesink, J.M., Verschueren, K.M., Zijlstra, J.M., Koene, H.R., Nijziel, M.R., Schimmel, E.C., Jongh, E. de, Ong, F., Boome, L.C. te, Rijn, R.S. van, Böhmer, L.H., Ta, B.D., Visser, H.P.J., Posthuma, E.F.M., Bilgin, Y.M., Muller, K, Kampen, D. van, So-Osman, C., Vermaat, J.S.P., Weijer, R.J. de, Kersten, M.J., Leeuwen, F.E. van, Schaapveld, M., Geurts, Y.M, Neppelenbroek, S.I.M., Aleman, B.M.P., Janus, C.P., Krol, A.D., Spronsen, D.J. van, Plattel, W.J., Roesink, J.M., Verschueren, K.M., Zijlstra, J.M., Koene, H.R., Nijziel, M.R., Schimmel, E.C., Jongh, E. de, Ong, F., Boome, L.C. te, Rijn, R.S. van, Böhmer, L.H., Ta, B.D., Visser, H.P.J., Posthuma, E.F.M., Bilgin, Y.M., Muller, K, Kampen, D. van, So-Osman, C., Vermaat, J.S.P., Weijer, R.J. de, Kersten, M.J., Leeuwen, F.E. van, and Schaapveld, M.
- Abstract
Contains fulltext : 304919.pdf (Publisher’s version ) (Open Access), BACKGROUND: The introduction of rituximab significantly improved the prognosis of diffuse large B-cell lymphoma (DLBCL), emphasizing the importance of evaluating the long-term consequences of exposure to radiotherapy, alkylating agents and anthracycline-containing (immuno)chemotherapy among DLBCL survivors. METHODS: Long-term risk of subsequent malignant neoplasms (SMNs) was examined in a multicenter cohort comprising 2373 5-year DLBCL survivors treated at ages 15-61 years in 1989-2012. Observed SMN numbers were compared with expected cancer incidence to estimate standardized incidence ratios (SIRs) and absolute excess risks (AERs/10 000 person-years). Treatment-specific risks were assessed using multivariable Cox regression. RESULTS: After a median follow-up of 13.8 years, 321 survivors developed one or more SMNs (SIR 1.5, 95% CI 1.3-1.8, AER 51.8). SIRs remained increased for at least 20 years after first-line treatment (SIR ≥20-year follow-up 1.5, 95% CI 1.0-2.2, AER 81.8) and were highest among patients ≤40 years at first DLBCL treatment (SIR 2.7, 95% CI 2.0-3.5). Lung (SIR 2.0, 95% CI 1.5-2.7, AER 13.4) and gastrointestinal cancers (SIR 1.5, 95% CI 1.2-2.0, AER 11.8) accounted for the largest excess risks. Treatment with >4500 mg/m(2) cyclophosphamide/>300 mg/m(2) doxorubicin versus ≤2250 mg/m(2)/≤150 mg/m(2), respectively, was associated with increased solid SMN risk (hazard ratio 1.5, 95% CI 1.0-2.2). Survivors who received rituximab had a lower risk of subdiaphragmatic solid SMNs (hazard ratio 0.5, 95% CI 0.3-1.0) compared with survivors who did not receive rituximab. CONCLUSION: Five-year DLBCL survivors have an increased risk of SMNs. Risks were higher for survivors ≤40 years at first treatment and survivors treated with >4500 mg/m(2) cyclophosphamide/>300 mg/m(2) doxorubicin, and may be lower for survivors treated in the rituximab era, emphasizing the need for studies with longer follow-up for rituximab-treated patients.
- Published
- 2024