Anti PD-1 antibodies nivolumab and pembrolizumab are checkpoint inhibitors widely used in metastatic melanoma with a 40% response rate. Little is known on predictive factors of response. Given the mechanism of action, we investigated whether features of natural history of melanoma correlated with response.
All melanoma patients treated with anti PD-1 between August 2014 and January 2016 in our center were retrospectively reviewed. Objective response to treatment was defined as complete response or partial response according to 1.1 RECIST criteria. Patients who received only 1 infusion were excluded. No clear definition of lymphatic or hematogenous dissemination in melanoma could be found in the literature. We defined lymphatic dissemination as exclusive lymphatic metastases or occurrence of a lymph node metastasis prior to a visceral metastasis. The rest was considered hematogenous dissemination. We excluded patients with only in-transit metastases (stage N2c). Time-in-node was defined as the delay between first lymphatic metastasis and first visceral metastasis. Time-to-treatment was defined as the delay between melanoma diagnosis and anti PD-1 therapy initiation.
65 patients were included (31 females; median age 65 years [21 to 90]). Treatment was initiated in patients having disease progression. 73% received pembrolizumab and 27% nivolumab. 28% of tumors harbored BRAF V600 mutations. Anti PD-1 was the first line therapy for 36% of the patients. Dissemination was lymphatic in 23 patients (37%) and hematogenous in 39 (63%). Objective response rate in the total population was 40%. Mean time-in-node was 26 months [2 to 132 months]. Mean time-to-treatment was 71 months [2 to 409 months]. There was no statistical correlation between response and either lymphatic vs hematogenous dissemination or time-in-node. Time-to-treatment was statistically associated with response (mean time-to-treatment 99 months in responders and 53 in non-responders, p = 0, 01). The same analysis with time from diagnosis to first line therapy was also positive (85 months in responders and 45 in non-responders, p = 0, 02).
Melanomas with slow natural history exhibit a higher sensitivity to nivolumab and pembrolizumab.
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Hôpital Cochin APHP
Hôpital Cochin APHP
All authors have declared no conflicts of interest.