839P - A retrospective study on the long-term survival and incidence of metachronous malignancies in advanced melanoma patients treated with immune checkpoint blockade (ICB)

Background

ICB (ipilimumab [IPI], nivolumab [NIVO], pembrolizumab [PEMBRO] or IPI/NIVO) improves long-term (>5y) survival of patients (pts) with unresectable stage III/IV melanoma. The incidence of metachronous malignancies (MM) in this population has not been reported.

Methods

We reviewed the medical files of prospectively identified unresectable stage III/IV melanoma pts treated with ICB at the Universitair Ziekenhuis Brussel. The probability for progression-free survival (PFS) and overall survival (OS) were calculated starting from the date of first ICB administration (by Kaplan-Meier estimates). The incidence of events (: melanoma progression, death or MM) were calculated by 1-year intervals and normalized to the weeks of pts-follow-up during the interval.

Results

Of the 292 eligible pts, 153 (52%) were female. Median age at first ICB was 57y [24–93]. A total of 219 (46%) IPI, 216 (46%) PEMBRO, 19 (4%) NIVO, and 17 (4%) IPI/NIVO treatments were administered; 81 pts (28%) were treated with IPI only, 85 (29%) with PEMBRO or NIVO only, and 126 (43%) with IPI and NIVO or PEMBRO . Median ICB duration was 44w (range 3-528); ICB was stopped electively in the absence of PD or AE in 166 (35%) pts, following an AE in 84 (18%) pts, PD in 177 (37%) pts, death in 42 (8,9%) pts, and 4 (0.8%) pts were lost to follow-up. Median PFS- and OS were 47w [95% CI, 33–60] and 83w (95% CI, 48–117) respectively; 3- and 5-y PFS-rates were 33% [27–39] and 26% [21–32]; 3- and 5y OS-rates were 41% [35–47] and 33% [27–39]. A total of 22 MM (13 cutaneous, 9 non-cutaneous) were diagnosed in 17 pts (5.8%). All pts underwent treatment with curative intent, there were no deaths due to MM. At the time of diagnosis of MM, 19 out of 22 pts were in a CR of their melanoma and 5 were treated with ICB. During the first 4y after the start of ICB dosing, the normalized incidence of melanoma PD was numerically higher than the of MM, from the 5^thy onwards, this ratio was inversed.

Conclusions

In this real-world study, long-term survival of ICB treated pts with unresectable stage III/IV melanoma resembles the outcome of prospective clinical trials. Beyond 5y, the incidence of melanoma PD is very low and numerically exceeded by a low-incidence of MM.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Universitair Zienehuis Brussel, Laarbeeklaan 101, 1090 Brussel, Belgium.

Funding

Department of Medical Oncology, Universitair Ziekenhuis Brussel, Brussels, Belgium.

Disclosure

J.K. Schwarze: Non-Financial Interests, Institutional, Other, costs associated with attending conferences: MSD and Amgen; Financial Interests, Institutional, Invited Speaker: Novartis. G. Awada: Non-Financial Interests, Institutional, Other, travel costs attending conferences: MSD, Novartis, Astellas, Pierre Fabre, Gilead; Financial Interests, Institutional, Invited Speaker: Novartis, Biocartis. S. Aspeslagh: Financial Interests, Institutional, Advisory Board: MSD, Sanofi, Roche, BMS, Pfizer, Galapagos. A. Rogiers: Financial Interests, Personal, Advisory Board: BMS. B. Neyns: Other, Institutional, Advisory Board: Novartis; Other, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Advisory Board: MSD, BMS, Pierre-Fabre; Financial Interests, Institutional, Invited Speaker: BMS, Biocartis; Financial Interests, Institutional, Research Grant: Amgen, Roche. All other authors have declared no conflicts of interest.