Hemophagocytic Lymphohistiocytosis as a Clinical Harbinger of Rapid Disease Progression in Multiple Myeloma During Daratumumab-Based Therapy.

Hemophagocytic lymphohistiocytosis (HLH) is rare in patients with multiple myeloma (MM), and its significance during anti-CD38-based therapy remains unclear. We report the case of a 76-year-old man diagnosed with MM and treated with daratumumab, lenalidomide, and dexamethasone who developed HLH before an aggressive clinical relapse. Autopsy revealed diffuse extramedullary plasma cell infiltration, despite the minimal morphological evidence of hemophagocytosis. This case highlights the fact that HLH during immune-modifying therapy should be recognized as a critical clinical harbinger of rapid disease progression in patients with CLL. The early identification of HLH is vital for detecting imminent disease progression and initiating immediate intervention before massive systemic involvement occurs.