BK Nephropathy in a Patient with Multiple Myeloma Receiving Bispecific Antibody Therapy

Introduction: Human Polyomavirus BK (BKV) is typically a benign virus with seroprevalence in the adult population of 50-90%, but has been associated with interstitial nephritis (nephropathy) in kidney transplant and hemorrhagic cystitis in hematopoietic stem cell transplant (HSCT) recipients. While rare, BKV nephropathy has been described in native kidneys, though mostly in solid organ transplant and HSCT recipients. We describe a case of native kidney BKV nephropathy in a patient receiving the T-cell redirecting bispecific antibody (BsAb), talquetamab, for multiple myeloma (MM). Case Description: A 66 yo woman with a history of relapsed/refractory IgG Kappa MM was admitted to our hospital for progressive kidney disease. Two months prior to her current admission, she had been started on talquetamab, a BsAb, for her 13th line of therapy for MM. Her creatinine at initiation of therapy was 2.45 mg/dL with a calculated eGFR of 22cc/hr/1.73m3. Her kidney function initially improved to a nadir of 1.89 mg/dL, but then over the duration of 2 months slowly increased to 4.47 mg/dL on day of admission. Her workup included well controlled light chains including a free kappa light chain 1.2mg/l and free lambda light chain1.6mg/l. Her Igs were low ,despite treatment 1 month prior with IVIG, with undetectable IgA+IgM, and IgG of 699 mg/dL. She had bland UA, UPCR of 600mg/g, and urine immunofixation with faint monoclonal IgG protein. Kidney biopsy was performed and revealed marked IFTA with remaining tubular cells showing foci of viral cytopathy changes with >10% positive for SV40 Ag, diagnosed as polyomavirus nephritis Banff class 3. No evidence of myeloma kidney was seen. Urine BKV PCR after showed >100,000,000 iu/mL, confirmed the diagnosis of BKV nephropathy. Talquetamab was stopped and she as treated with monthly IVIG, but unfortunately never recovered kidney function. Discussion: BsAbs are a novel therapy with two different binding domains, which bind one domain to a T-cell antigen (Ag) and another to a B-cell maturation Ag, thus allowing for T-cell destruction of MM cells. BsAbs have significant risk for infection, and some providers utilize prophylactic anti-virals and antibiotics with therapy. While infectious complications of BsAbs are common, BKV nephropathy has not be described, and thus this is the first description to our knowledge.