Clinical Trials Research Fellow Barts Cancer Centre, Queen Mary University of London London, England, United Kingdom
Background: Immune checkpoint inhibitors (ICIs) are well established in the treatment of metastatic renal cell carcinoma (mRCC). Although early-onset ( < 12 months) immune-related adverse events (irAEs) are well described, data on late-onset irAEs occurring at ≥12 months of therapy are lacking.
Methods: A single-site retrospective audit of mRCC patients receiving ICI-based therapy for ≥12 months. ICI-based therapies included ICI monotherapy and combination therapy with CTLA-4 or tyrosine kinase inhibitors (TKI). Best response to ICI-based therapy and irAEs were described.
Results: Between January 2014 and December 2022, 127 patients received ICI-based therapy, of which 39% (49/127) received treatment for ≥12 months. 18% (9/49), 33% (16/49) and 49% (24/49) received ICI monotherapy, ICI/CTLA-4 and ICI/TKI combination, respectively. At data cut-off, 71% (35/49) were alive. 16% (8/49), 65% (32/49), and 18% (9/49) achieved CR, PR and SD, respectively. 41% (20/49) subsequently developed PD. Overall, 61 irAEs were observed in 76% (37/49) patients receiving treatment for ≥12 months. From these, 61% (37/61) occurred at < 12 months, 38% (23/61) were new irAEs at ≥12 months, and 1/61 was an irAE recurrence after 12 months. 32% (12/37) of early-onset and 57% (13/23) of late-onset irAEs required corticosteroids. No ICI-related deaths occurred. From late-onset irAEs, 78% (18/23) were grade 1/2 and 22% (5/23) were grade 3/4. Grade ≥3 late-onset irAEs included colitis (n=1), proctitis (n=1), tubulointerstitial nephritis (n=1) and transaminitis (n=2). All these events required corticosteroids. Three patients discontinued treatment and the remainder restarted therapy after irAE resolution. All patients with late-onset grade ≥3 irAEs responded to therapy (CR in 2/5, PR in 3/5). Two patients with late-onset grade 2 irAEs (bullous pemphigoid and inflammatory arthritis) also required treatment discontinuation.
Conclusions: Although irAEs are less frequent after 12 months of ICI-based therapy, they remain clinically relevant requiring treatment interruption and discontinuation. Patients require ongoing monitoring irrespective of duration of therapy.