Treatment-specific risk of subsequent malignant neoplasms in five-year survivors of diffuse large B-cell lymphoma

Y M Geurts, S I M Neppelenbroek, B M P Aleman, C P M Janus, A D G Krol, D J van Spronsen, W J Plattel, J M Roesink, K M S Verschueren, J M Zijlstra, H R Koene, M R Nijziel, E C Schimmel, E de Jongh, F Ong, L C J Te Boome, R S van Rijn, L H Böhmer, B D P Ta, H P J VisserE F M Posthuma, Y M Bilgin, K Muller, D van Kampen, C So-Osman, J S P Vermaat, R J de Weijer, M J Kersten, F E van Leeuwen, M Schaapveld*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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 cyclophosphamide/>300 mg/m doxorubicin versus =2250 mg/m /=150 mg/m , 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 cyclophosphamide/>300 mg/m 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.
Original languageEnglish
Article number102248
Number of pages10
JournalESMO Open
Volume9
Issue number2
DOIs
Publication statusPublished - 12 Feb 2024

Keywords

  • alkylating agents
  • anthracyclines
  • diffuse large B-cell lymphoma
  • radiotherapy
  • subsequent neoplasms
  • survivorship

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