1820MO - Predisposition, clinical characteristics and management of immune checkpoint inhibitor-induced nephritis: A series of 190 cases

Background

Immune checkpoint inhibitors (ICI) used can lead to an array of immune-related adverse events (irAEs). Nephritis is considered to be an uncommon with a incidence of 2-7%. The factors predisposing to developing ICI-induced nephritis remain unclear as does the reversibility and management of steroid-refractory toxicity.

Methods

This retrospective cohort observational study identified who developed ICI-induced nephritis at the Clatterbridge Cancer Centre, UK from January 2020 to February 2023. Patients were registered with the centralised specialist pan-regional immunotherapy toxicity team. CTCAE Grade 1 nephritis was considered low-grade nephritis, while Grade 2 or above was termedhigh-grade nephritis. Statistical analysis was conducted using IBM SPSS statistics, v28 utilising Chi Squared and Cramer V analysis.

Results

190 patients developed ICI-induced nephritis, an incidence of 7% (190/2645). Pre-nephritis features such as primary disease, immunotherapy regime, use of combined therapy, ethnicity, gender, or smoking status were not associated with nephritis. The the use of nephrotoxic drugs, specifically PPIs and ACEi (P<0.001) predisposed for nephritis. Low-grade nephritis was less likely to require corticosteroids (P<0.001). However, if required, a shorter course of treatment was needed (P<0.001). There was an association between higher grade and lack of return to baseline renal function (P<0.001). Use of second-line immunosuppression was used in 13% (24/190) patients to treat refractory nephritis, 23 of whom received mycophenolate mofetil (MMF). 38% (9/24) of these returned to baseline/normal renal function and 67% (16/24) had improvement in creatinine to <1.5x ULN impairment.

Conclusions

This large series illustrates that there is a concomitant medication predisposition to ICI-induced nephritis and consideration of the clinical need for PPIs should be considered prior to commencing ICI treatment. Additionally clinical categorisation into low, high and refectory nephritis is likely to be helpful in treatment. Finally MMF illustrated benefit in managing refractory nephritis with the majority resolving to clinically acceptable levels.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

A.C. Olsson-Brown: Financial Interests, Personal, Invited Speaker: BMS, MSD, Roche, AstraZeneca, GSK, Ipsen, Boehringer Ingelheim, Novartis, Merck. N. Garbutt: Financial Interests, Personal, Invited Speaker: BMS. J.J. Sacco: Financial Interests, Personal, Advisory Board, I have received honoraria for participation on advisory boards, both personal and to institution: Immunocore; Financial Interests, Institutional, Advisory Board: Immunocore, Replimune; Financial Interests, Personal, Advisory Board: Delcath; Financial Interests, Institutional, Local PI: Immunocore, Replimune, Qbiotics, MSD; Financial Interests, Institutional, Research Grant: Immunocore, AstraZeneca, BMS; Other, Other, Travel and conference costs: MSD. All other authors have declared no conflicts of interest.