P192 | PERSISTENT CYTOKINE RELEASE SYNDROME IN PATIENTS RECEIVING BISPECIFIC ANTIBODY THERAPY FOR MULTIPLE MYELOMA: A CASE SERIES

Bispecific antibodies such as Talquetamab have shown efficacy in relapsed/refractory multiple myeloma (RRMM), with cytokine release syndrome (CRS) being a common early toxicity. However, data on persistent or recurrent CRS during ongoing therapy are limited. We report three cases of RRMM patients treated with Talquetamab who developed prolonged, cyclic CRS episodes during maintenance dosing. Case 1: A 65-year-old male experienced recurrent fevers 24–48 hours after each outpatient administration. Infectious evaluations—including blood cultures, chest imaging, CMV and COVID-19 PCR, and echocardiography—were consistently negative. CRS episodes were resolved with tocilizumab (8 mg/kg) and corticosteroid premedication (dexamethasone 16 mg/day, tapered over 3 days). Case 2: A 71-year-old female similarly developed monthly febrile episodes unresponsive to prednisone (25 mg/day). Infectious workups, including blood cultures, beta-D-glucan, galactomannan, and transesophageal echocardiography, ruled out infections. Tocilizumab administration was required at each episode for symptom control. Case 3: A 75-year-old female developed both infectious (e.g., COVID-19, bronchitis) and non-infectious febrile episodes. Careful differential diagnosis was achieved through serial imaging, cultures, and viral assays. Non-infectious febrile episodes consistent with CRS responded promptly to tocilizumab. Across all cases, CRS episodes recurred approximately every 30–40 days, were unresponsive to antipyretics or steroids alone, and required IL-6 blockade for resolution. No progressive disease was observed during CRS episodes, and treatment with Talquetamab was continued without interruption. Our findings suggest that persistent cyclic CRS may occur beyond the initial dosing phase in heavily pretreated patients, highlighting the need for careful infectious exclusion and tailored immunosuppressive management. Tocilizumab remains effective for recurrent CRS without compromising anti-myeloma activity. Further studies are needed to define the pathophysiology and optimal management of delayed CRS.