Unveiling the Dual Threat: Glofitamab-Induced AKI via Tumor Lysis and Cytokine Release Syndromes

Introduction: Glofitamab, a monoclonal CD20-directed CD3 T-cell engager, treats refractory diffuse large B-cell lymphoma (DLBCL) but can induce acute kidney injury (AKI) via tumor lysis syndrome (TLS) and cytokine release syndrome (CRS). We report a case of a patient who developed AKI secondary to glofitamab infusion through both mechanisms simultaneously. Case Description: A 78-year-old male with DLBCL presented with AKI. His baseline serum creatinine (SCr) was 1.6-1.8 mg/dL. Treated with 6 rounds of R-CHOP regimen, with some improvement 6 months ago. 6 weeks before admission, he developed spontaneous TLS, treated with rasburicase and IV fluids & was found to have metastatic recurrence of DLBCL. His tumor was treated with gemcitabine and oxaliplatin to no avail. Glofitamab was then started for DLBCL treatment. Due to CRS risk, the patient received obinutuzumab pretreatment. 30 minutes into the test dose, he experienced nausea, lethargy, and hypotension, leading to hospitalization. After stabilization, he tolerated the therapeutic dose of obintutuzumab 5 days later. Later, he received his first glofitamab infusion. Within 12 hours, he developed symptoms of CRS (fever, tachycardia, and hypotension) and was sent to ICU, received IV fluids, dexamethasone, and tocilizumab, which assisted with stabilizing his vitals. Key lab tests of CRS and TLS are in Table 1. For TLS, he was treated with IV fluids, sodium zirconium cyclosilicate, and sevelamer. His CRS resolved first, allowing him to be transferred back to the floor from the ICU. He continues to be treated for TLS, is recovering well, and is currently preparing for a 2nd dose of glofitamab. Discussion: Glofitamab is a novel immunotherapy for DLBCL that can induce both CRS and TLS. While reports exist of these syndromes occurring simultaneously in response to other therapies, to our knowledge, glofitamab has not been previously reported to do so. As both CRS and TLS can cause AKI, albeit through different mechanisms, nephrologists should closely monitor patients receiving glofitamab for both syndromes.