e21001 Background: Efficacy of Vb in the treatment of mm has been established. We aimed to analyze characteristics of pts achieving LTR to Vb in order to identify potential predictive factors of prolonged benefit. Methods: We collected information about pts affected by BRAF V600 mutated mm treated with Vb at Medical Oncology Unit of Istituto Nazionale dei Tumori, Milan, Italy, from 09/2010 to 08/2014. LTR was defined as clinical or radiological benefit longer than 14 months (mos). Biological data about circulating lymphocyte subpopulations and CCL2 levels were also determined. Results: 46 pts (26 men, 20 women) were identified. Median age was 58 years. ECOG performance status was 0 in 44 pts. Disease stage was M1a in 14 pts, M1c in 20 pts. 8 pts had high serum LDH levels and 5 brain metastases at baseline. 41 pts harbored BRAF V600E mutation, 5 V600K. Median follow up was 47 mos. 5 pts had received adjuvant interferon; 9 pts had been treated with up to 3 lines for metastatic disease (either chemotx or ipilimumab). According to RECIST 1.1, 22% of pts showed complete response (CR), 50% partial response and 22% stable disease. Notably, all CRs were maintained for more than 2 years. 26 pts progressed, mostly (38%) with brain metastases; 16 of them continued tx beyond progression. Median duration of response was 33 mos, being significantly longer in M1a than in M1c (44 versus 28 mos). Median PFS was 32.5 mos; median OS was not reached. All pts experienced at least 1 adverse event (AE); the AEs were moderate or severe in 22% of cases. 19 pts underwent dose reduction, but no discontinuation due to AEs was observed. After 6 mos of tx, pts with LTRs had less myeloid derived suppressor cells (CD11b+ CD14+) and more memory Th1 cells (CD8+ CXCR3+) if compared with pts not bearing LTRs. The same pts after 1 mo of tx showed lower plasma levels of CCL2, a marker of acquired resistance to Vb. Conclusions: Vb can induce LTRs in a subset of pts with mm also in presence of unfavorable prognostic factors, though M1a pts are more likely to obtain prolonged benefit. Toxicity is frequent, but manageable with limited dose reductions. Exploratory biological analyses suggest an immunomodulatory effect of Vb and the existence of circulating biomarkers of LTR.