Post-Transplant Double Malignancy: Multiple Myeloma and Papillary Renal Cell Carcinoma—A Case Report

<b>Background and Clinical Significance:</b> Kidney transplant recipients have a 2-4-fold higher cancer risk than the general population. The sequential occurrence of multiple myeloma (MM) and native-kidney renal cell carcinoma (RCC) is rare and creates competing priorities between anti-myeloma efficacy and allograft preservation. <b>Case Presentation:</b> A 54-year-old woman with a 2020 living-donor kidney transplant presented in 2024 with bone pain and shoulder swelling. Low-dose whole-body CT showed multiple punched-out osteolytic lesions. Work-up revealed IgG-κ M-protein 38.5 g/L and 25% clonal plasma cells; cytogenetics showed a complex karyotype (R-ISS III). First-line bortezomib/cyclophosphamide/dexamethasone (VCd) was given while maintaining tacrolimus plus low-dose steroid. After four cycles, she achieved very good partial response (M-protein 42.3 to 5.6 g/L) with stable graft function. Follow-up imaging detected a large exophytic mass in the native right kidney; nephrectomy confirmed papillary RCC, type II. Later, the myeloma progressed with epidural extension causing cord compression. Second-line daratumumab/carfilzomib/dexamethasone (DKd) and palliative spine radiotherapy were initiated. The course was complicated by opportunistic infection and pancytopenia, and the patient died in January 2025. <b>Conclusions:</b> Vigilant post-transplant cancer surveillance-including native-kidney RCC-tailored immunosuppression, and multidisciplinary coordination are critical. VCd with tacrolimus may be feasible when graft preservation is prioritized; however, relapsed high-risk MM on DKd carries substantial infectious risk and a guarded prognosis.