Abstract
Panniculitis and vitiligo-like lesions have been recently identified as rare cutaneous side effects of the combination of BRAF and MEK inhibitors, a standard of care in metastatic and locally advanced BRAF V600 mutated melanoma. An immune-mediated mechanism has been advocated in the pathogenesis of these skin lesions. Herein we retrospectively reviewed our institutional experience with the aim to explore the association between the occurrence of panniculitis and vitiligo-like lesions during combination therapy with dabrafenib (D) and trametinib (T) and outcome of advanced melanoma patients. Among 52 consecutive BRAF V600 mutated melanoma patients submitted to DT in our center, 12 (23%) developed immune related skin lesions (IRSLs): 8 panniculitis and 4 vitiligo. Patients with IRSLs diagnosis obtained a better disease response (83% versus 25%) (p = 0.001) than their counterpart and had a longer progression free survival and overall survival. The association of IRSLs and lower risk of disease progression (HR 0.19; CI 95% 0.04–0.90; p = 0.043) was confirmed after adjusting for major prognostic factors in multivariate analysis. IRSLs might represent an easy predictive surrogate marker for treatment response and favourable outcome in melanoma patients submitted to DT combination therapy.
Highlights
IntroductionBaseline serum lactate dehydrogenase (LDH) and number of metastatic sites strongly predicts overall survival (OS) and progression-free survival (PFS) of DT treated patients [4] and patients with normal LDH and less than three metastatic sites are expected to have a 5-years OS rate of 51% [5]
We report a case series of patients who developed immune related skin lesions (IRSLs) during DT therapy with the aim to correlate these events with disease response and patient progression-free survival (PFS)
The use of combination regimens with BRAF and MEK inhibitors has contributed to modify the prognosis of patients with BRAF V600 mutated melanomas and preclinical and clinical evidences available, suggest that the long term efficacy of these therapies could be attributed in part to an immune-modulating effect [16]
Summary
Baseline serum lactate dehydrogenase (LDH) and number of metastatic sites strongly predicts OS and PFS of DT treated patients [4] and patients with normal LDH and less than three metastatic sites are expected to have a 5-years OS rate of 51% [5]. These findings notwithstanding, the prediction of prognosis of individual melanoma patients treated with DT remains difficult and new prognostic markers are needed, in addition beside BRAF mutation, no additional predictive parameters of DT efficacy have been up to now identified
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