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

Summary

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.