Improving health related quality of life (HRQoL) assessment and immune related adverse event (irAE) classification with novel tools in renal cancer.
Authors: Nally Elizabeth , Ainsworth Gemma , Brown Sarah R. , Bergerot Cristiane Decat , Wells Connor , Young Matthew Nicholas , Westerman Tanith , Coca Sara , Jackson-Spence Francesca , Szabados Bernadett Emma , Pal Sumanta Kumar , Powles Thomas , Vasudev Naveen ,   Sarah Brown
Published: February 2025

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Background:
HRQoL tools and adverse event criteria were designed around outdated therapies and require re-evaluation in the era of immune checkpoint inhibitors (ICI). Attempts have been made to create a novel HRQoL tool (Bergerot et al) but this has not been validated in prospective data sets. To our knowledge no attempts have been made to re-evaluate current toxicity grading systems. Data from PRISM, a randomized ph2 trial which explored scheduling of 1
st
line ipilimumab/nivolumab in advanced renal cell carcinoma (RCC), was used to validate these novel tools.
Methods:
HRQoL (EORTC QLQ-C30 & FKSI-19) and irAE data graded using common terminology criteria for adverse events (CTCAE) were analysed in treatment naïve patients with advanced RCC recruited to PRISM. Patients were randomised 2:1 to 4 doses of ipilimumab 12-weekly (modified) or 3-weekly (standard) in combination with nivolumab. The novel QoL tool, created with patient engagement and expert input, was prospectively tested and compared with scores for FKSI-19 (0-76) and QLQ-C30 (0-100). irAEs (graded 1-5 CTCAEv5) were reclassified by patient advocates into 3 groups; life changing (LC), significant (S), non-significant (NS). These were further classified into short term (ST) or long term (LT).
Results:
In PRISM 192 patients were randomised 2:1 (128 modified, 64 standard schedule). HRQoL scores were available for 157 patients at baseline, week 13 and 25. Baseline scores were comparable across all 3 (QLQ-C30, FKSI-19, novel tool) tools. IMDC good risk patients had higher QOL scores at baseline across all three questionnaires compared to intermediate/poor risk (FSKI 64 vs 58, QLQC-30 86 vs 77, novel tool 59 vs 53,
p
<0.05). Only the novel tool showed significantly improved QoL (57 v 51,
p
>0.05) at 13 weeks. There was no correlation between occurrence of grade 3/4 irAEs and reduction in QOL as reported in PRISM. QoL scores in patients with progressive disease were worse across all tools (FSKI 52.3 v 58.9, QLQC-30 60.3 v 75.2, novel tool 48 v 56.4,
p
<0.02). 1158 irAEs were reported and reclassified. All grade 1 irAEs were deemed NS. The table shows the frequency of significant or life changing toxicity as perceived by patients. Incidence of life changing and significant toxicity was 15% and 24% respectively, which was associated with reduction in HRQoL across all tools.
Conclusions:
Here we describe the frequency of significant or life changing toxicity associated with ICI which will help clinicians in describing risk/benefit ratios to patients. Refining these tools facilitates more accurate future data collection in trials which better reflects the patient experience.

irAE
Life changing (LC)
Significant short term (SST)
Significant long term (SLT)
Non-significant (NS)

Grade 2n=281
17 (6%)
17 (6%)
10 (4%)
237 (84%)

Grade 3n=122
14 (12%)
53 (43%)
9 (7%)
46 (38%)

Grade 4n=8
2 (25%)
4 (50%)
1 (12.5%)
1 (12.5%)