Abstract 836P
Background
Treatment with programmed cell death protein (PD-1) blocking antibodies substantially improves prognosis of melanoma patients. However, there is still limited evidence how baseline demographics influence treatment efficacy in real world practice.
Methods
This registry-based observational study evaluated the therapy outcome of 1046 melanoma patients who were treated with single agent PD-1 inhibitors in the advanced setting. Demographic and baseline variables were analysed in respect to differences in overall survival (OS), time to next treatment after PD-1 inhibitor treatment (TTNT) and other outcome variables.
Results
For melanoma-specific OS, many factors were not significantly relevant. However, among the statistically significant factors (age, ECOG, LDH, line of treatment and AJCC stages M1c and M1d) the age effect was of particular interest. When grouping patients into three age groups (<70/70-80/>80) there was a higher risk of melanoma related death for patients aged 70-80 years (multivariable HR (95% CI): 1.51 (1.02-2.2)) and patients older than 80 years (multivariable HR 1.78; 95% CI 1.04-3.0). Median melanoma specific OS was not reached for patients younger than 70 years, 33.6 (31.7–nr) months for patients between 70 and 80 years, and 30.3 (20.4–nr) for patients older than 80 years. For TTNT a significant effect of age could not be observed. Objective response rate (ORR) was slightly elevated in the age group 70-80 years (47%; p = 0.04) as compared to younger patients (39.6%) and patients older than 80 years (39.7%). Also, median PFS (95% CI) was 9.9 (7.6-14.1) months for patients younger than 70 years, 12.9 (8.6-18.4) months for patients between 70 and 80 years and 9.3 (6.9-12.3) for patients older than 80 years.
Conclusions
The different survival outcomes showed less benefit of PD-1 inhibitor therapy in patients older than 80 years compared to younger patients. The most likely explanation could be a generally reduced immunoreactivity with increasing age. However, ORR and PFS were slightly higher in the age group of 70-80 years as compared to younger patients. These results suggest a complex relationship between age and response to immune checkpoint inhibition.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
EUMelaReg gGmbH, Berlin, Germany.
Funding
Novartis AG; Merck & Co., Inc.; Bristol Myers Squibb.
Disclosure
M. Weichenthal: Financial Interests, Personal, Advisory Board: MSD, BMS, Roche, Novartis, Sanofi. I. Svane: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, Novartis; Financial Interests, Personal, Invited Speaker: MSD, Pierre Fabre, Novartis, Roche, BMS, MSD; Financial Interests, Personal, Stocks/Shares, Cofounder and Founder warrents: IO Biotech; Financial Interests, Institutional, Research Grant: Adaptimmune, Enara Bio, Lytix Biopharma, TILT Biotherapeutics; Financial Interests, Institutional, Funding: Evaxion; Non-Financial Interests, Principal Investigator: BMS, Roche, TILT Biotherapeutics, Lytix Biopharma, Novartis. L. Kandolf Sekulovic: Non-Financial Interests, Personal, Invited Speaker: MSD; Financial Interests, Personal, Invited Speaker: Novartis, Roche, BMS, AbbVie. J. Mangana: Financial Interests, Personal, Advisory Board: Merck-Pfizer, Merck Sharp & Dohme, Novartis, Roche, Amgen, Bristol Myers and Squibb, L'oreal, Pierre Fabre; Financial Interests, Personal, Other, Travel grant: Ultrasun, L'oreal, Merck Sharp & Dohme, Bristol Myers and Squibb, Pierre Fabre; Financial Interests, Institutional, Research Grant, The melanoma registry database of the Department of Dermatology has been partially supported by an unrestricted grant to the University of Zurich from Amgen, Novartis, BMS, MSD and Pierre Fabre: Novartis, BMS, Pierre Fabre, Amgen, MSD. I. Lugowska: Financial Interests, Personal, Invited Speaker, The reports of clinical trials: ROCHE, BMS, Macrogenics, Amgen; Financial Interests, Institutional, Other, Research grants: ROCHE; Financial Interests, Institutional, Other, Research grant: Agenus; Financial Interests, Personal and Institutional, Invited Speaker: Agenus, Roche, BMS, Janssen, Astra, Incyte, Macrogenics, Checkpoint Inhibitors, Celon, Pfizer, MSD, Debio; Non-Financial Interests, Project Lead: MSCI; Non-Financial Interests, Advisory Role, Board Member: EORTC. P. Mohr: Financial Interests, Personal, Invited Speaker: BMS, Merck Sharpe & Dohme, Roche, Novartis, Pierre Fabre, Sanofi, Beiersdorf, Amgen; Financial Interests, Personal, Advisory Board: BMS, Merck Sharpe & Dohme, Roche, Amgen, Sanofi, Pierre Fabre; Financial Interests, Institutional, Research Grant: Merck, BMS, Novartis. E. Espinosa: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Pierre Fabre; Other, Personal, Other, congress invitation: MSD; Financial Interests, Institutional, Research Grant: Roche. H.J. Gogas: Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Invited Speaker: MSD, BMS, Novartis, Pierre Fabre, SANOFI; Financial Interests, Invited Speaker: Amgen, Replimune; Financial Interests, Institutional, Invited Speaker: Amgen, MSD, BMS, Replimune, Iovance; Financial Interests, Institutional, Research Grant: BMS, Pfizer. E. Ellebæk: Financial Interests, Personal, Invited Speaker: Pierre Fabre, BMS, Novartis; Other, Travel and conference expenses: MSD, Pierre Fabre. I. Gavrilova: Financial Interests, Personal, Invited Speaker: MSD, Roche, Merck Sharpe & Dohme, Novartis, BMS, Sanofi; Financial Interests, Personal, Advisory Board: MSD, Roche, Merck, Novartis, BMS, Sanofi; Financial Interests, Personal, Speaker’s Bureau: MSD, Roche, Merck, Novartis, BMS, Sanofi. E. Muñoz Couselo: Financial Interests, Personal, Advisory Board: BMS, Novartis, Sanofi, Pierre Fabre, Sun Pharma, MSD; Financial Interests, Personal, Invited Speaker: Novartis, Roche, BMS, Sanofi, MSD, Pierre Fabre. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfzer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Invited Speaker: Polish Society of Surgical Oncology; Non-Financial Interests, Officer: ASCO; Non-Financial Interests, Invited Speaker, President Elect: Polish Oncological Society. P.A. Ascierto: Financial Interests, Personal, Other, Consultant and Advisory Role: BMS, Roche Genentech, MSD, Novartis, Pfizer/Array, Merck Serono, Pierre Fabre, AstraZeneca, Sun Pharma, Sanofi, Idera, Sandoz, Immunocore, 4SC, Nektar, Boehringer Ingelheim, Regeneron; Financial Interests, Personal, Other, Consultant Role: Italfarmaco; Financial Interests, Personal, Other, Advisory Role: Eisai, Seagen; Financial Interests, Personal, Other, Consultant Role: Daiichi Sankyo, Pfizer, Oncosec, Nouscom, Lunaphore; Financial Interests, Personal, Other, Consultant role: Medicenna, Bio-AI Health; Financial Interests, Personal, Advisory Board, Consultant and Advisory Role: Dohme, iTeos; Financial Interests, Institutional, Funding, Clinical trial and translational research: BMS; Financial Interests, Institutional, Funding, Clinical Trial: Roche Genentech, Pfizer/Array, Sanofi; Non-Financial Interests, Leadership Role, President since 2010: Fondazione Melanoma Onlus Italy; Non-Financial Interests, Leadership Role, President since 2014: Campania Society of ImmunoTherapy of Cancer (SCITO) Italy; Non-Financial Interests, Other, Member of Steering Committee since 2016: Society for Melanoma Research (SMR); Non-Financial Interests, Invited Speaker, November 2017 - December 2021: Society for Immunotherapy of Cancer (SITC); Non-Financial Interests, Member: ASCO, SITC, EORTC Melanoma Cooperative Group, AIOM, SMR; Other, Travel Support: MSD. R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, Alligator, MaviVAX SA, touchIME, T3 Pharma, Pfizer. D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, Novartis, MSD, Roche, Merck Serono, Sanofi, Merck, Novartis, BMS, MSD, 4SC, Nektar; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Roche, Merck Serono, Immunocore, 4SC, Pierre Fabre, Sanofi/Regeneron, Array Biopharma, Pfizer, Philogen, NEKTAR, Sandoz, Neracare; Financial Interests, Institutional, Research Grant: Novartis, BMS, MSD, Array/Pfizer; Financial Interests, Institutional, Invited Speaker: Novartis, BMS, MSD, Pierre Fabre, Sanofi, Roche, Philogen, 4SC, Nektar; Non-Financial Interests, Invited Speaker: EORTC-MG. L. Bastholt: Financial Interests, Institutional, Funding: MSD. All other authors have declared no conflicts of interest.