Development of immunity-related adverse events correlates with baseline clinical factors, survival and response to anti-PD-1 treatment in patients with inoperable or metastatic melanoma

Abstract

Background

The relationship between immune related adverse events (irAEs) and efficacy is not definitively proven, and data on the relationship between irAE and treatment efficacy are contradictory.

Material and methods

Five hundred ninety-three consecutive patients with unresectable or metastatic melanoma treated in the first line with anti-PD-1 (nivolumab or pembrolizumab) between January 2016 and December 2019 were enrolled in the study.

Results

Statistically significant differences were demonstrated between the group of patients without and with irAE in median OS and PFS (p < .0001 both) and also in OS between the group of patients without irAE and patients with irAE within 3, 6, and 9 months from the start of anti-PD-1 therapy (p = .0121, p = .0014, p < .0001; respectively) and PFS (p = .0369, p = .0052, p = .0001; respectively). A statistically significant relationship was demonstrated between the occurrence of irAE and the location of the primary tumor (skin vs. mucosa vs. unknown; p = .0183), brain metastasis (present vs. absent; p = .0032), other locations (present vs. absent, p = .0032), LDH (normal vs. elevated; p = .0046) and stage according to TNM (p = .0093).

Conclusion

The occurrence of irAE was associated with longer OS, PFS, and more frequent response to treatment. IrAE occurred statistically significantly more often in patients with mucosa primary tumor, with normal LDH levels, without brain metastases, stages III, M1a, and M1b.

Keywords:

• Melanoma
• irAE
• immunotherapy
• anti-PD-1 therapy
• immune-related adverse events

Disclosure statement

PR Financial Interests: Blueprint Medicines, Advisory Board, Personal, <€5,000; BMS, Invited Speaker, Personal, €5,001 - €10,000, honoraria for lectures; BMS, Advisory Board, Personal, <€5,000; Merck, Advisory Board, Personal, <€5,000; Merck, Invited Speaker, Personal, <€5,000; MSD, Invited Speaker, Personal, €5,001 - €10,000, honoraria for lectures; MSD, Advisory Board, Personal, <€5,000; Novartis, Invited Speaker, Personal, €5,001 - €10,000; Pierre Fabre, Invited Speaker, Personal, <€5,000, honoraria for lectures, Pierre Fabre, Advisory Board, Personal, <€5,000; Sanofi, Advisory Board, Personal, <€5,000 Sanofi, Invited Speaker, Personal, <€5,000; BMS, Funding, Institutional, Financial interest, research grant for institution; Pfizer, Research Grant, Institutional, Financial interest, research grant for ISS; Non-financial Interests: ASCO, Officer; Polish Society of Surgical Oncology, Member of Board of Directors., JM — advisory board from BMS, MSD; lectures – BMS; GSK, Roche, MSD, Novartis, Pierre-Fabre; travel reimbursement: BMS, GSK, Roche, MSD, Novartis, Pierre-Fabre.. Fees and honoraria: AMC, TK, JC — BMS, Novartis, Roche, Merck; BCS, RD — BMS, Novartis, Roche, Pierre Fabre, MSD; RS, JS — BMS, MSD, Astellas Pharma; JM — BMS, GlaxoSmithKline, Roche, MSD, Novartis, Pierre Fabre; NKK —BMS, Roche; MZ — BMS, MSD, Novartis, for lectures and Advisory Boards outside of the scope of the study. KP, BZ, KG, SK, TZ — none declared