From Unexplained Fever to a Second Malignancy: Peripheral T-cell Lymphoma Following Long-term Olaparib Maintenance Therapy in Ovarian Cancer

Background Fever of unknown origin (FUO) presents a common clinical challenge, with lymphoma being a significant neoplastic cause. Olaparib, a cornerstone in ovarian cancer maintenance therapy, has well-documented hematologic toxicities. However, its potential association with peripheral T-cell lymphoma (PTCL) remains unreported. Case Presentation: We report the case of a 77-year-old woman with advanced ovarian cancer on long-term maintenance therapy with olaparib and letrozole for over three years, who presented with fever and progressive cytopenia. Comprehensive infectious and rheumatologic workups were negative. Cell-free DNA sequencing revealed complex chromosomal abnormalities. ¹⁸ FDG PET/CT showed diffuse, intense skeletal hypermetabolism (SUVmax 16.0). Subsequently laboratory findings, including extreme hyperferritinemia (> 33511.2 ng/mL), elevated sIL-2R, hypertriglyceridemia, and hypofibrinogenemia, fulfilled the criteria for hemophagocytic lymphohistiocytosis (HLH). Bone marrow biopsy ultimately confirmed the diagnosis of peripheral T-cell lymphoma (PTCL) with marrow involvement. Despite discontinuing olaparib and initiating therapy for HLH and lymphoma, the patient's condition deteriorated rapidly, leading to death within one month of admission. Conclusion The case represents the first reported temporal association between long-term olaparib therapy and the development of PTCL in an ovarian cancer patient. It underscores the importance of considering secondary hematologic malignancies, including lymphoma, in patients on novel targeted therapies who present with unexplained FUO and cytopenias.