This finding is in line with our data reporting resistance to RHM in U266 cells which are indeed MYC defective [67] and with other previous observations that highlighted a higher mutational load in relapsed refractory MM (RRMM) and a crucial role exerted by MYC expression as a predictive factor to DDR inhibitors response, [68–70], further confirming that Alt-NHEJ function may be more complex than a simple back-up system. This evidence concerns the gene MYC and Miyoshi myopathy.