3300 A phase 1b/2 study of ribociclib (LEE011; CDK4/6 inhibitor) in combination with binimetinib (MEK162; MEK inhibitor) in patients with NRAS-mutant melanoma

Abstract

s S663 and refractory MM patients a significant humoral immune response against proteins related with these three conditions. Materials and Methods: We studied repository serum with clinical data included in MGUS, naive and refractory MM. We performed a systematic multivariate analysis of proteins overexpressed in monoclonal gammopathy as representative of a potential start to create preventive vaccines for MM and in refractory cancer patients who progress despite treatment. We found four potential oncogenic drivers such as HIF-1 alpha, RAD51, Sox2 and Mcl-1. Afterwards we performed an antigen–specific indirect ELISA for both IgG and IgA using recombinant proteins to interrogate human MGUS naive and refractory MM serum and demonstrated if they were immunogenic. Results: Using indirect ELISA both antigen specific IgG and IgA using recombinant proteins with the four proteins we only found a statistical difference for anti-Mcl-1 specific IgG in MGUS (p = 0.01), naive MM (p = 0.005) and relapsed MM (p = 0.05). For anti-Mcl-1 IgA we found in MGUS (p=0001), naive MM (p = 0.002) and relapsed MM (p = 0.01). Here, we showed that even in refractory MM the antigenspecific humoral immune response was detected and it was clear that patients with the highest immune responses had better clinical outcomes in terms of OS. Discussion: MM is a challenging hematological malignancy and immune therapy is a good possibility for treatment either to prevent recurrence or in combination to improve the outcomes of the current standard of care treatment. We showed that one out of the four proteins had biological and clinical relevance in MGUS, naive and relapsed MM is immunogenic both for IgG and IgA. We will move forward to prepare a peptide vaccine and test animal immunogenicity for Mcl-1. Also it could be a good approach in combination with standard of care treatment in progressive or active disease to improve clinical outcomes. No conflict of interest. Proffered Paper Session (Monday, 28 September) Melanoma and Skin Cancer