Potential Role for Bispecific T Cell Engagers (TCEs) in the Treatment of Light-Chain Cast Nephropathy

Introduction: Light chain cast nephropathy (LCCN) is the major cause of acute kidney injury(AKI) in patients with multiple myeloma. The presence of AKI with LCCN portends a poor prognosis and recovery of renal function is directly related to the speed and magnitude by which the serum free light chain(FLC) levels are lowered. Current therapy includes combinations of proteasome inhibitors, corticosteroids, immunomodulators, and anti-CD38 antibodies. More recently, TCEs have emerged as a treatment option for relapsing/refractory multiple myeloma (RRMM) with significant response rates and progression free survival. Here, we present a case of a patient who presented with RRMM and LCCN that was treated successfully with a TCE. Case Description: The patient is an 80-year-old male with refractory IgG kappa multiple myeloma diagnosed in 2021 who was status post 4 previously lines of therapy. He presented with generalized weakness and fatigue and was found to have a serum creatinine (Cr) of 3.1 mg/dL from a baseline of 0.8-1.0 mg/dL two months prior. Workup was notable for bicarbonate 19 mmol/L, calcium 8.9 mg/dL, urine spot protein to Cr ratio of 2400 mg/g, Urine spot albumin to Cr ratio of 123.1 mg/g. SPEP with a 0.8g/dl M protein identified as IgG kappa (k), with k FLC elevation to 117 mg/dL from 18 mg/dL two months prior. UPEP also confirmed the presence of IgG k measured at 986 g/day. No alternative etiology of AKI was found and a presumptive diagnosis of LCCN was made and was initiated on teclistamab one week after admission. His Cr at the time of discharge was 2.2 mg/dL. Approximately one week after his first treatment dose, his k FLC had decreased to 13.8 mg/dl. His Cr 2 weeks later had improved to 1.3 mg/dL and at three months was 0.9 mg/dL. Approximately 8 months later, he remains on teclistamab and is currently in remission. Discussion: The use of immunotherapy including CAR-T therapy and TCEs has demonstrated promising results in patients with RRMM. Teclistamab is the first bispecific B-cell maturation antigen (BCMA)-directed CD3 TCE. This case demonstrates the potential efficacy of Teclistamab in rapidly improving both the hematological and renal parameters in LCCN by rapid reduction of pathogenic FLC.