Time interval from primary melanoma to first distant recurrence in relation to patient outcomes in advanced melanoma

Abstract

Since the introduction of BRAF(/MEK) inhibition and immune checkpoint inhibition (ICI), the prognosis of advanced melanoma has greatly improved. Melanoma is known for its remarkably long time to first distant recurrence (TFDR), which can be decades in some patients and is partly attributed to immune-surveillance.We investigated the relationship between TFDR and patient outcomes after systemic treatment for advanced melanoma. We selected patients undergoing firstline systemic therapy for advanced melanoma from the nationwide Dutch Melanoma Treatment Registry. The association between TFDR and progression-free survival (PFS) and overall survival (OS) was assessed by Cox proportional hazard regression models. The TFDR was modeled categorically, linearly, and flexibly using restricted cubic splines. Patients received anti-PD-1-based treatment (n = 1844) or BRAF(/MEK) inhibition (n = 1618). For ICI-treated patients with a TFDR <2 years, median OS was 25.0 months, compared to 37.3 months for a TFDR >5 years (P = .014). Patients treated with BRAF(/MEK) inhibition with a longer TFDR also had a significantly longer median OS (8.6 months for TFDR <2 years compared to 11.1 months for >5 years, P = .004). The hazard of dying rapidly decreased with increasing TFDR until approximately 5 years (HR 0.87), after which the hazard of dying further decreased with increasing TFDR, but less strongly (HR 0.82 for a TFDR of 10 years and HR 0.79 for a TFDR of 15 years).Results were similar when stratifying for type of treatment. Advanced melanoma patients with longer TFDR have a prolonged PFS and OS, irrespective of being treated with first-line ICI or targeted therapy.

A prediction model for response to immune checkpoint inhibition in advanced melanoma

“…Also, TFDR in the model, a for which we recently demonstrated to be is associated with survival in ICI-treated advanced melanoma patients. 19 Our study has several limitations. First, using observational data from a nationwide cohort leads inevitably to indication bias.…”

“…In the final model, location of primary melanoma, primary melanoma type and presence of satellites and/or in‐transit metastases were selected as predictor variables. Also, TFDR was included in the final model, a variable for which we recently demonstrated to be is associated with survival in ICI‐treated advanced melanoma patients 19 …”

“…We incorporated the variable ‘presence of symptomatic brain metastases’ in the variable ‘stage of disease’: M1D stage was subcategorized either as ‘M1D‐non‐symptomatic’ or ‘M1D‐symptomatic’. The TFDR was defined as the time from diagnosis of the primary tumour to first detection of metastatic disease 19 . For primary melanoma characteristics, the following variables were included as candidate predictor variables: location, histological subtype, presence of ulceration, presence of satellites and/or in‐transit metastases (at time of primary diagnosis) and Breslow thickness.…”

“…The TFDR was defined as the time from diagnosis of the primary tumour to first detection of metastatic disease. 19 For primary melanoma characteristics, the following variables were included as candidate predictor variables: location, histological subtype, presence of ulceration, presence of satellites and/or intransit metastases (at time of primary diagnosis) and Breslow thickness.…”

A prediction model for response to immune checkpoint inhibition in advanced melanoma.

“…Also, TFDR was included in the final model, a variable for we demonstrated to be is associated with survival in ICI-treated advanced melanoma patients. 19 Our has several First, using observational data from a nationwide cohort leads inevitably to indication bias. This is, for reflected the response rates in our study.…”