Second primary cancers in lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia-cumulative burden without generalized excess cancer risk.

Second primary cancers (SPCs) are a survivorship concern in lymphoplasmacytic lymphoma/Waldenström macroglobulinaemia (LPL/WM), but estimates may be influenced by competing mortality and surveillance. We assessed cumulative incidence, relative risk and predictors of SPCs. We studied 521 patients diagnosed with LPL/WM in Region Zealand, Denmark, during 2000-2023. Cancers diagnosed >6 months before or after diagnosis were classified as prior malignancies and SPCs, respectively. Cumulative incidence was estimated with death as a competing event. Standardized incidence ratios (SIRs) and absolute excess risks (AERs) used regional rates. SPC predictors were evaluated using Fine-Gray and Cox models. Median age was 72 years and median follow-up was 8.1 years. Prior malignancy was present in 64 patients (12.3%); 68 (13.1%) developed an SPC. Cumulative incidence was 9.3% at 5 years and 14.6% at 10 years; 166 patients (31.9%) died without a preceding SPC. With 1-year latency, overall cancer risk was not increased (SIR 1.09, 95% confidence interval [CI] 0.84-1.40; AER 21.3 per 10 000 person-years). Haematological cancers showed borderline excess risk, driven by myelodysplastic syndrome. No covariates were associated with SPC risk. SPCs are clinically relevant in LPL/WM, although excess risk appears selective rather than broadly increased. Long-term surveillance should consider myeloid malignancies.