Therapy‐Related Acute Myeloid Leukemia Following Plasma Cell Leukemia: A Case Report and Literature Review

With the improvement of survival in multiple myeloma (MM), therapy-related acute myeloid leukemia (t-AML) has emerged as a clinically relevant second primary malignancy (SPM). We report a case of MM evolving into t-AML after multi-agent chemotherapy and review the literature on therapy-related leukemias in MM. We report a case of a patient diagnosed with primary plasma cell leukemia (IgG-λ type, R-ISS stage III) who achieved complete remission following maintenance therapy with daratumumab, lenalidomide, and dexamethasone after receiving a treatment regimen based on proteasome inhibitors. The patient progressed to therapy-related acute myeloid leukemia 18 months later, and we present the clinical features. Additionally, we conducted a literature review. Given the patient's age and debilitated physical condition, treatment with azacitidine combined with venetoclax was administered. Following the treatment, the patient developed grade IV post-chemotherapy myelosuppression complicated by infection and extensive ischemic stroke. Despite aggressive supportive care, the patient's condition continued to deteriorate and he succumbed in August 2025. This case illustrates the leukemogenic risk of cytotoxic exposure in MM, highlights the adverse genetic profile of therapy-related AML, and emphasizes the need for vigilant monitoring and preventive strategies in long-term MM survivors.