TECLISTAMAB AND NIVOLUMAB: A SYNERGISTIC KIDNEY STORM - A CASE OF ACUTE INTERSTITIAL NEPHRITIS WITH DUAL IMMUNOTHERAPY

Introduction:

Acute interstitial nephritis (AIN) is an immune-related adverse event (irAE) seen with immune checkpoint inhibitor (ICI) use. Teclistamab is a bispecific antibody that engages T-cells and is indicated for the treatment of relapsed or refractory multiple myeloma (RRMM).  There is a paucity of safety information about combination immunotherapies. We report a patient with RRMM, on ICI therapy for a concurrent squamous cell carcinoma (SCC), who developed AIN shortly after Teclistamab initiation, suggesting a potential interaction between these agents.

Methods:

Case description

A 68-year-old male with IgG kappa MM diagnosed 5 years prior, with pre-existing non-proteinuric chronic kidney disease, presented to the clinic with fatigue and a new acute kidney injury (AKI), and was diagnosed with irAEs due to Teclistamab - immune effector cell-associated neurotoxicity syndrome (ICANS) and cytokine release syndrome. Three weeks prior, he was started on Teclistamab for RRMM and received 3 step-up doses on days D -21, D -18 and D -15. Additionally, he was on nivolumab therapy for 3 years for SCC of the oropharynx.

At presentation, serum creatinine (SCr) was 2.17 mg/dL compared to his baseline of 1.2mg/dL before Teclistamab therapy. Kappa free light chain (FLC) level and kappa/lambda FLC ratio were 65.3 mg/dL and >502, respectively. Urinalysis was negative for blood. Urine protein-creatinine ratio was 1.05 mg/mg and albumin-creatinine ratio was 69 mg/g. Urine retinol binding protein-creatinine ratio was elevated at 21212 μg/g, >200 times the upper limit of normal. Cytokine panel was notable for elevated TNF-α, IL-6, IL-10, IL-18, and soluble IL-2 receptor levels. Obstructive and autoimmune etiologies were ruled out. 

He was started on Dexamethasone 10mg twice daily, initially for ICANS, with escalation to methylprednisolone 250 mg IV on day 3 due to concern for AIN and lack of response. A kidney biopsy confirmed AIN along with a few kappa light chain restricted casts causing tubular injury. With higher doses of glucocorticoids, the patient’s SCr improved to a nadir of 1.83 mg/dL. Medications associated with AIN like proton pump inhibitors (PPI) and trimethoprim-sulfamethoxazole (TMP-SMX), which he was taking for about 3 years, were discontinued. Unfortunately, he developed a plasma cell leukemia after which he chose to transition to hospice care.

Results:

This patient’s kidney function remained stable at baseline despite being on multiple MM therapies, PPI, TMP-SMX, and Nivolumab for about 3 years and with elevated kappa FLC (35-60 mg/dL) over the preceding 3 weeks. The timing of the rise in SCr following initiation of Teclistamab suggests that it may have a synergistic effect in inducing AIN when used alongside other medications. AIN associated with ICI is characterized by infiltration of kidney tissue by activated T-cells, leading to the release of pro-inflammatory cytokines. Since Teclistamab also activates T-cells and induces cytokine release, we hypothesize that the combined effect of these mechanisms may have contributed to the AKI observed in this case.

Conclusions:

There are no prior reports of AKI in patients treated concurrently with ICI and Teclistamab. This patient case underscores the importance of monitoring kidney function vigilantly in patients receiving these agents. Potential interaction between these two drug classes warrants further research.

I have no potential conflict of interest to disclose.

I did not use generative AI and AI-assisted technologies in the writing process.