Immune checkpoint inhibition (ICI) has changed the landscape of melanoma therapy. However, not much is known about the long-term outcomes and durability of response in patients who experienced a complete response (CR) under ICI. It is important to monitor this patient population due to the financial toxicity and the immune-related adverse events (irAEs) associated with prolonged treatment.
We evaluated unresectable stage IV melanoma patients treated with first-line ICI between 2013 and 2018 outside of a clinical trial. Overall survival (OS) and progression-free survival (PFS) were assessed. irAEs occurring after six months of treatment and response to ICI rechallenge were recorded. Additionally, the prognostic value of clinicopathologic features was investigated.
43 (12.1%) patients experienced CR. 40 (93%) patients discontinued therapy. Three (7%) patients are still receiving treatment without having a progressive disease (PD). The median age at the time of CR was 74 [IQR; 66-77] years old. 26 patients (65%) received anti-PD-1 monotherapy and 14 patients (35%) received nivolumab plus ipilimumab. The median follow-up (FUP) after CR was 49 [IQR; 43-57] months. The median treatment duration was 22 [IQR; 17–24] months, and the median time from CR to therapy ending was 10 [IQR; 1–17] months. Median PFS and OS were not reached (95% CI; NR-NR). 5-year PFS and OS after CR was 79% (95% CI; 62%-89%) and 83% (95% CI; 60%-93%), respectively. Age below 77 years at CR (p=0.043) was linked to a better prognosis in the univariable Cox regression. Neither the total length of treatment (p=0.754) nor the treatment duration after CR were associated with prognosis (p=0.398). Second-line ICI was administered to eight patients, and disease control was seen in 5 (64%). 10 (25%) of the patients experienced late toxicities, with two of them being severe.
In our cohort, CR under ICI seems to be a surrogate marker for long-term survival. The duration of treatment was not associated with either PFS or OS, but the optimal duration of therapy in patients achieving CR is not established. Biomarkers are required to help identify patients at risk of relapse among complete responders but also patients who can safely stop therapy after CR.
The authors.
Has not received any funding.
U. Leiter-Stoppke: Financial Interests, Personal, Advisory Role: MSD, Novartis, Roche, Sanofi, Sun Pharma; Financial Interests, Institutional, Funding: MSD. I. Thomas: Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Institutional, Invited Speaker: BMS, Pfizer, MSD, Amgen, Novartis, Sanofi, 4SC, AstraZeneca, Biontech, Genentech, Roche, Biotech, Curevac, HUYA, Incyte, Idera, Iovance, Infla-Rx, Kartos, Nektar, Regeneron; Non-Financial Interests, Personal, Member: ADO, DKG, EADO. A. Forschner: Financial Interests, Institutional, Funding: Bristol Myers Squibb-Stiftung Immunonkologie; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb, MSD Oncology, Novartis, Pierre Fabre, Roche Pharma AG; Financial Interests, Personal, Other: Bristol-Myers Squibb, Novartis, Pierre Fabre, Roche Pharma AG; Financial Interests, Personal, Invited Speaker: CeGaT, MSD Oncology, Bristol-Myers Squibb, Novartis, Roche Pharma AG. L. Flatz: Financial Interests, Personal, Ownership Interest: Hookipa Pharma; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb, Novartis, Sanofi; Financial Interests, Personal, Advisory Role: Bristol-Myers Squibb, Novartis, Sanofi; Financial Interests, Institutional, Funding: Hookipa Pharma; Financial Interests, Personal, Royalties: Hookipa Pharma. T.M.S. Amaral: Financial Interests, Personal, Invited Speaker: CeCaVa, BMS, Novartis, Pierre Fabre; Financial Interests, Institutional, Funding: Novartis, Neracare, Sanofi, Skyline-Dx; Financial Interests, Institutional, Research Grant: Novartis, iFIT; Non-Financial Interests, Personal, Member: Portuguese Society for Medical Oncology, Portuguese Society of Medical Oncology - Young Oncologists Group, ASCO; Other, Personal, Other, Clinical expert: Infarmed. All other authors have declared no conflicts of interest.