Complete responders to checkpoint inhibitors in advanced melanoma: Relapse risk factors, and patients' outcomes.

Abstract

9550 Background: Since the development of immune checkpoint inhibitors (ICI) for advanced melanoma, a small group of patients with an excellent and durable response has emerged. Complete response (CR) is achievable in about 10-20% of the patients and seem to have an excellent prognosis. However, 10 to 15% of them might relapse eventually. Our main objective was to determine factors associated with relapse after a CR to ICI in advanced melanoma. The second objective was to describe relapse modalities and tumor response to subsequent treatments. Methods: We performed a single-center, retrospective study, in 141 patients with a CR to ICI for advanced melanoma, treated at Gustave Roussy (France) from January 2010 to June 2020. CR was confirmed on two consecutive CT-scanner or PET-CT at least 3 months apart. Characteristics of the patients at diagnosis, during and after treatment were compared in both groups: CR with relapse and CR without relapse. The LASSO analysis, a statistical analysis using lambda penalization coefficient for prognostic studies, was performed regarding the many statistical variables analysed. Results: At data analysis, immunotherapy was interrupted in 94.3% of the patients and the median follow-up was 3.5 years since immunotherapy discontinuation. Eventually, 18 of 141 patients (12.8%) had relapsed and 126 (87.2%) had not. The statistical analysis identified three factors associated with melanoma recurrence: prior lines of therapy, the type of melanoma and the mutation status. Indeed, relapse risk was higher in patients with wild type melanoma (as opposed to BRAF or NRAS mutant melanoma), with a mucosal, acral or unknown primitive melanoma and who received prior lines of treatment. Other factors such as demographical characteristics, tumor burden, metastasis localization, type or grade of toxicity, pseudo progression, type of ICI, treatment duration, use of a complementary local treatment and pursuit/discontinuation of immunotherapy were not statistically associated with the duration of the complete response. In case of melanoma recurrence, reintroduction of immunotherapy provided tumor response in half of our patients: 13 of the 18 relapsing patients received immunotherapy after melanoma recurrence; allowing 3 CR, 2 partial responses and 1 stable disease. One third of the relapsing patients eventually died of disease progression. Conclusions: This study confirmed the excellent prognosis of CR to ICI in advanced melanoma, even after treatment discontinuation and identified 3 baseline factors associated with a risk of relapse: absence of BRAF or NRAS mutation, primary of acral, mucosal or unknown origin, and previous lines of therapy. Rechallenge with ICI was effective in 50% of the patients.

Efficacy of Immune Checkpoint Inhibitor (ICI) Rechallenge in Advanced Melanoma Patients’ Responders to a First Course of ICI: A Multicenter National Retrospective Study of the French Group of Skin Cancers (Groupe de Cancérologie Cutanée, GCC)

“…In this study, we present the largest cohort of melanoma patients who were rechallenged with anti-PD1 antibodies for progressive disease after achieving disease control with ICI. Indeed, most of the available data on the efficacy of ICI rechallenge come from small patient groups, including clinical trials and real-life cohorts with a BORR ranging from 12% to 54%, and a DCR ranging from 46% to 87.5% (Table 3) [9,[15][16][17][18][19][20]22,23]. The efficacy of ICI rechallenge in our cohort was high, similar to the retrospective studies [16][17][18][19][20]23] and very close to the Keynote-006 trial [15].…”

“…Indeed, most of the available data on the efficacy of ICI rechallenge come from small patient groups, including clinical trials and real-life cohorts with a BORR ranging from 12% to 54%, and a DCR ranging from 46% to 87.5% (Table 3) [9,[15][16][17][18][19][20]22,23]. The efficacy of ICI rechallenge in our cohort was high, similar to the retrospective studies [16][17][18][19][20]23] and very close to the Keynote-006 trial [15]. We observed that the BORR to ICI rechallenge reported by Betof et al was much lower compared to other studies (12% with anti-PD1 and 33% with ipilimumab plus nivolumab) [22].…”

“…There are many data regarding the tolerance of ICI rechallenge after the occurrence of treatment AEs but data are scarce regarding the efficacy of ICI rechallenge for recurrent or progressive disease after initial disease control with a previous course of ICI [10][11][12][13]. Indeed, data, including clinical trials and real-life cohorts, came from small patient groups data and the efficacy of ICI rechallenge varies [6,9,[14][15][16][17][18][19][20].…”