Early survival follow-up suggests that BTKi-BCL2i retains efficacy for TP53 aberrant (and possibly umIGHV) CLL; the major utility of upfront BTKi-BCL2i combination may be for younger patients with high-risk disease, accepting heightened risks of hypertension and low but not insignificant cardiac arrhythmia. This evidence concerns the gene TP53 and B-cell chronic lymphocytic leukemia.