In the prospective O-CLL training cohort, a Cox regression model indicated IGHVumut genes, 11q and 17p deletions, elevated β2M, Rai stage I-II, NOTCH1 mutations and LDT ≤ 12 months as independently associated with shorter TTFT, thus confirmed the prognostic value of LDT in the era of new prognostic indicators. Here, B2M is linked to B-cell chronic lymphocytic leukemia.