Risk of synchronous and second primary malignancies in transplant-ineligible patients with multiple myeloma treated with lenalidomide

An increased risk of second primary malignancies (SPMs) was reported for transplant-ineligible (TI) patients with newly diagnosed multiple myeloma (NDMM) exposed to lenalidomide (Len), with the caveats that Len was often coexposed to alkylating agents and the studies did not exclude synchronous malignancies (SyMs). We aimed to evaluate the respective SyM over SPM risks in TI patients with NDMM treated with Len as frontline therapy. We conducted a high-resolution, population-based cancer registry study, which allowed completeness of the primary end point (SyMs and SPMs) without reporting bias, and provided a cohort more representative of real-life than those in clinical trials. The inclusion period started recently (2018) due to the reimbursement of Len in France. Additional malignancies (AdMs) diagnosed ≤4 months of MM diagnosis were defined as SyMs; those diagnosed >4 months were considered SPMs. The person-year approach was used with an indirect standardization. With a median follow-up of 36 months, 360 consecutive TI patients with NDMM were identified, including 174 treated with Len. In total, 35 patients (9.7%) had an AdM (standardized incidence ratio [SIR], 2.17), 16 (4.4%) had an SyM (SIR, 8.20), and 19 (6.4%) had an SPM (SIR, 1.15). Among patients treated with Len, 12 (6.9%) had an SPM (SIR, 1.28), and cumulative incidence was 3.6% at 3 years. TI patients with NDMM have a high risk of being codiagnosed with an SyM possibly explained by examinations performed at the time of MM diagnosis. In contrast, patients treated with Len who were never exposed to conventional chemotherapy did not seem to have an increased risk of SPM compared with the general population.