Outcome of Elective Checkpoint Inhibitor Discontinuation in Patients with Metastatic Melanoma Who Achieved a Complete Remission: Real-World Data

Abstract

Checkpoint inhibitor therapy for metastatic melanoma has dramatically improved outcomes. Currently, 20 to 40% of treated patients achieve lengthy remissions. It is not clear whether patients in remission require ongoing therapy or if treatment can be safely discontinued. A retrospective chart review was performed of patients who underwent elective treatment discontinuation after two negative scans three months apart. Of 132 checkpoint inhibitor-treated patients, 46 achieved a complete response (34.8%) and electively discontinued therapy. The progression-free survival was 97.5% at 1 year and 94.7% at 3 years following treatment discontinuation. The median duration of follow-up was 26 months. In total, 4 of 46 individuals (8.7%) eventually relapsed (median time to relapse: 27 months). The median disease-specific survival of the entire cohort was not reached and was 100% at 4 years from the start of therapy. Two patients eventually died, one from melanoma and the other from an unrelated illness. We have identified an elective treatment discontinuation strategy that is generalizable to a variety of checkpoint inhibitor ± targeted therapy regimens. We found that most complete remissions remained durable after elective treatment discontinuation. We hypothesize that this approach could decrease potential drug toxicities, reduce the treatment-related financial burden, and improve patients’ quality of life.

Checkpoint Inhibitors Immunotherapy in Metastatic Melanoma: When to Stop Treatment?

“…We analyzed 10 studies focused on the discontinuation of anti-PD-1 therapy, published from 2018 to 2022, involving a total of 1199 patients. Two prospective clinical trials [ 1 , 9 , 20 ] and eight retrospective studies [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] were evaluated. Responses to checkpoint inhibitors were mainly assessed according to RECIST 1.1 criteria [ 1 , 9 , 20 , 21 , 24 , 25 , 27 , 28 ].…”

“…Two prospective clinical trials [ 1 , 9 , 20 ] and eight retrospective studies [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ] were evaluated. Responses to checkpoint inhibitors were mainly assessed according to RECIST 1.1 criteria [ 1 , 9 , 20 , 21 , 24 , 25 , 27 , 28 ]. Only in one study were immuno-related response criteria used [ 22 ].…”

“…In a recent retrospective, monocenter study, Perez et al recognized the possibility of discontinuing ICI therapy in patients who have obtained a CR [ 28 ]. Of 132 patients, 46 achieved a CR and discontinued treatment after a second lot of radiographic evaluations performed 3 months later.…”

“…The limitation of this study is that patients were not treated homogeneously. Twenty-three patients were treated with the combination nivolumab plus ipilimumab and 10 patients with the addition of an anti-BRAF or anti-MEK at first progression with ICI therapy [ 28 ]. The main features of the studies are summarized in Table 1 .…”

“…It should be noted that, despite a major response, about 25–30% of patients are at risk of recurrence in a time period ranging from a few months to some years from treatment cessation, and, when retreated, they respond less than in the first line setting: about 20% of response rate for patients retreated with anti-PD-1 as a single agent and about 30% when used in combination with anti-CTLA-4 [ 1 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 ]. It is noteworthy, however, that patients who have CR at discontinuation have a higher probability of response to retreatment (about 50 percent) [ 1 ].…”