1109P - Association of clinical features with long-term survival in patients with melanoma who responded to distinct checkpoint inhibitors

Background

In metastatic melanoma, patients responding to checkpoint inhibitors (CPIs) may develop acquired resistance. This study explores clinical characteristics associated with favorable long-term outcomes among CPI responders.

Methods

We utilized the Danish Metastatic Melanoma Database (DAMMED), a national registry collecting prospective data on all patients undergoing systemic treatments. We retrospectively collected baseline, treatment, and clinical outcome information for patients treated with CPIs up to 4th line (ocular melanoma, reinductions and clinical trials excluded).

Results

A total of 3,120 patients were analyzed, receiving treatments with ipilimumab (ipi, n=821, ORR 19%), anti-PD-1 (PD-1, n=1557, ORR 47%), or ipilimumab+nivolumab (ipi+nivo, n=742, ORR 48%). Of these, 1,253 patients achieved partial response (PR) or complete response (CR). Median follow-up was 4.6 years. Estimated 5-year outcomes demonstrated excellent long term survival rates for unselected patients achieving CR (Table). Table: 1109P

In multivariable analyses on patients receiving PD1 ± ipi, factors such as no previous adjuvant therapy (point HR between 0.50 and 0.55) and CR (point HR between 0.11 and 0.16) but not other baseline characteristics such as treatment line, disease stage, elevated LDH, performance status or presence of brain metastases were independently associated to improved PFS, OS and melanoma-specific survival (MSS). Propensity-score matched analysis showed superimposable long-term survival curves for responders to ipi+nivo or PD-1.

Conclusions

Unselected patients achieving CR to any CPI regimen exhibit excellent 5-year MSS, exceeding 93%. Among responders to PD1 ± ipi, key baseline features such as elevated LDH or presence of brain metastases do not predict outcomes; long-term outcomes are comparable across CPI regimens. These findings can guide follow up strategies for responders to CPI.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

National Center for Cancer Immune Therapy, Copenhagen University Hospital, Herlev, Denmark.

Funding

Independent Research Fund Denmark.

Disclosure

E. Ellebaek: Financial Interests, Personal, Invited Speaker: Pierre Fabre, BMS, Novartis, MSD, Pfizer; Other, Other, Travel and conference expenses: MSD, Pierre Fabre. T.H. Borch: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb. C.H. Ruhlmann: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb, Helsinn Healthcare, MSD, Pharmanovia; Financial Interests, Personal, Other, Consultant: Astellas Pharma; Financial Interests, Institutional, Coordinating PI, Funding for a clinical trial: Helsinn Healthcare, Novo Nordisk Foundation. L. Bastholt: Non-Financial Interests, Advisory Role, Scientific committee under Danish Medicines Agency regarding new treatments of melanoma, skin cancer and thyroid cancer: Danish Medicines Agency. I.M. Svane: Financial Interests, Personal, Advisory Board: Novartis, Mendus, Instil Bio; Financial Interests, Personal, Invited Speaker: MSD, BMS, Sanofi, Takeda; Financial Interests, Personal, Writing Engagement: MSD; Financial Interests, Personal, Stocks/Shares, Cofounder and Founder warrents: IO Biotech; Financial Interests, Institutional, Research Grant: Adaptimmune, Enara Bio, Lytix Biopharma, TILT Biotherapeutics, Asgard Therapeutics, IO Biotech; Financial Interests, Institutional, Funding: Evaxion; Financial Interests, Institutional, Other, drug for investigator driven trial: BMS; Non-Financial Interests, Principal Investigator: BMS, Roche, TILT Biotherapeutics, Lytix Biopharma, Novartis, Immunocore, MSD. M. Donia: Financial Interests, Personal, Other, Advisor: Achilles Therapeutics; Non-Financial Interests, Other, Sub-investigator of clinical trial with connected translational research: Bristol Myers Squibb; Non-Financial Interests, Personal, Proprietary Information, Proprietary data access: Bristol Myers Squibb; Non-Financial Interests, Personal, Proprietary Information, Proprietary Data Access: Genentech; Other, Other, Chairman of the Melanoma and Non-melanoma Skin Cancer Scientific Committee: Danish Medicines Council (Medicinrådet). All other authors have declared no conflicts of interest.