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

• MM patients have a high-risk of synchronous malignancies (SyM) co-diagnosis, possibly explained by exams performed at MM diagnosis.

• The risk of SPM-related to lenalidomide, not differentiating from SyM to SPM, was likely overestimated.

An increased risk of SPM (second primary malignancies) was reported for newly diagnosed multiple myeloma transplant ineligible (NDMM-TI) exposed to lenalidomide (Len), with the caveats that Len was often co-exposed to alkylating-agents and the studies did not exclude SyM (synchronous malignancies). We aimed to evaluate the respective SyM over SPM risks in NDMM-TI treated in front-line with Len. We conducted a high-resolution population-based cancer registry study, which allowed completeness of the primary endpoint (SyM and SPM) without reporting bias, and to guarantee a cohort more representative of real-life than clinical trials. The inclusion period started recently (2018) due to the reimbursement of Len in France. Additional malignancies (AdM) diagnosed ≤4 months after MM diagnosis was defined as a SyM, and >4 months an SPM. The person-year approach was used with an indirect standardization. With a median follow-up of 36 months [95%CI 40-44], 360 consecutive NDMM-TI were identified, including 174 treated with Len. In total, 35 (9.7%) patients had an AdM (SIR 2.17 [95%CI 1.51-3.02]), 16 (4.4%) had a SyM (SIR 8.20 [95%CI 4.68-13.31]) and 19 (6.4%) patients had a SPM (SIR 1.15 [95%CI 0.69-1.79]). For NDMM-TI treated with Len, 12 (6.9%) had a SPM (SIR 1.28 [95%CI 0.66-2.23]) and cumulative incidence was 3.6% at 3 years [95%CI 1.5-7.2%]. NDMM-TI have a high-risk of being co-diagnosed with a SyM possibly explained by exams performed at MM diagnosis. NDMM-TI treated with Len, never exposed to conventional chemotherapy, did not seem to have an increased risk of SPM compared with the general population.