Lambda Light Chain Multiple Myeloma in a 47-Year-Old Female Patient on Long-Term Clozapine Therapy

Clozapine is an atypical antipsychotic used for treatment-resistant schizophrenia and schizoaffective disorder. While its hematologic toxicities, such as neutropenia and agranulocytosis, are well-documented, emerging studies suggest a rare but concerning association between long-term clozapine use and hematologic malignancies. We present a case of multiple myeloma (MM) in a 47-year-old woman with a 10-year history of clozapine use for schizoaffective disorder. The patient was admitted with orthostasis, fatigue, and acute kidney injury following a gastrointestinal illness. Initial workup revealed severe anemia, a pelvic mass later attributed to uterine fibroids, and extensive lytic bone lesions on imaging. Hematologic evaluation demonstrated a markedly elevated lambda free light chain level, suppressed kappa/lambda ratio, and rouleaux formation on peripheral smear. Bone marrow biopsy confirmed 90% lambda light chain-restricted plasma cells, consistent with MM. The patient responded to cyclophosphamide-bortezomib-dexamethasone (CyBorD) chemotherapy and was discharged to continue outpatient treatment. This case underscores the importance of maintaining clinical vigilance for hematologic malignancies in patients on long-term clozapine therapy, particularly when presenting with unexplained renal dysfunction, anemia, or lytic bone lesions. Although leukemias and lymphomas are reported more than MM, this case adds to the limited literature describing MM in the context of chronic clozapine exposure and highlights the need for further pharmacovigilance and research into long-term hematologic risks of atypical antipsychotics.