Although the prognostic value of the CLL-IPI risk model on OS diminishes in patients treated upfront with novel agents, the retained prognostic impact of B2M on OS alone both in patients with CKD and in those treated with novel drugs strongly suggests the implementation of B2M as a promising covariate in up-coming CLL risk models predicting OS in the treatment era of novel drugs. This evidence concerns the gene B2M and B-cell chronic lymphocytic leukemia.