144P - Association between immune-related adverse events and survival in metastatic renal cell carcinoma treated with nivolumab plus ipilimumab

Background

Immune check inhibitor (ICI) combination therapy with an anti-PD-1 inhibitor and an anti-CTLA-4 inhibitor is used as first-line therapy in metastatic renal cell carcinoma (mRCC). Immune-related adverse events (irAEs) are known to be associated with better survivals in various cancer types. However, the association between the irAEs and survivals remains unestablished in mRCC patients treated with ICI combination therapy.

Methods

We performed a retrospective review of patients with mRCC treated with nivolumab plus ipilimumab from multiple centers between September 2018 and February 2021. We investigated the incidence of irAEs and the association of irAEs with overall survivals (OS) and progression-free survivals (PFS). Multi-system irAEs were defined as ≥Grade 2 irAEs developing to +1 organ system. To avoid lead time bias, we also performed the landmark analysis.

Results

A total of 129 patients, 107 of clear cell RCC and 22 of non-clear RCC, were assessed. The median age and follow-up was 67 years (range 28–87) and 12.3 months (range 0.1–36.3), and 92 patients (71%) were male. Pituitary irAEs (n=35) were the most frequently observed ≥Grade 2 irAEs followed by thyroid (n=23), skin (n=21), hepatic (n=14), pulmonary irAEs (n=9). A total of 39 patients (30%) developed multi-system irAEs. Pituitary and thyroid irAEs were significantly associated with improved OS (Hazard ratio [HR] 0.25, p=0.0018; HR 0.35, p=0.039) but not other organ-specific irAEs while only pituitary irAEs were associated with improved PFS (HR 0.49, p=0.018). Multi-system irAEs were associated with improved survivals compared to no or one ≥Grade 2 irAEs (OS: HR 0.16, p<0.0001 or HR 0.56, p=0.25; PFS: HR 0.23, p<0.0001 or HR 0.36, p=0.00063). In the 4-month landmark analysis, multi-system irAEs were significantly associated with improved OS compared to no ≥Grade 2 irAEs (HR 0.36, p=0.048).

Conclusions

Pituitary and thyroid irAEs were the most frequently observed irAEs in mRCC patients treated with ICI combination therapy. One third of patients developed irAEs involving multiple organ systems, however, which was associated with improved survivals.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

Y. Miura: Financial Interests, Personal, Invited Speaker: Takeda, MSD, Bristol Myers Squibb, Ono Pharmaceutical, Merk Biopharma, Eisai, Astellas Pharma; Financial Interests, Institutional, Principal Investigator: Ono Pharmaceutical, MSD. All other authors have declared no conflicts of interest.