Second Primary Malignancies in Chronic Lymphocytic Leukaemia; Skin, Solid Organ, Haematological, and Richter’s Syndrome

Chronic lymphocytic leukaemia (CLL) is invariably accompanied by some degree of immune failure. CLL patients have a high rate of second primary malignancy (SPM) compared to the general population. We comprehensively documented the incidence of all forms of SPM including skin cancer (SC), solid organ malignancy (SOM), second haematological malignancy (SHM), and separately Richter’s Syndrome (RS) across all therapy eras. Among the 517 CLL/SLL patients, the overall incidence of SPMs with competing risks were SC 31.07%, SOM 25.99%, SHM 5.19% and RS 7.55%. Melanoma accounted for 30.3% of SC. Squamous cell carcinoma (SCC), including 8 metastatic SCCs, was 1.8 times more than basal cell carcinoma (BCC), a reversal of the typical BCC:SCC ratio. The most common SOM were prostate (6.4%) and breast (4.5%). SHM included 7 acute myeloid leukaemia and 5 myelodysplasia of which 8 were therapy-related. SPMs are a major health burden with 44.9% of CLL patients with at least one, and apart from SC, associated with significantly reduced overall survival. Dramatic improvements in CLL treatment and survival have occurred with immunochemotherapy and targeted therapies but mitigating SPM burden will be important to sustain further progress.