Ibrutinib plus venetoclax combination trial designs. Ibrutinib was administered for 2 to 3 cycles, each lasting for 28 days, to induce a debulking effect, disrupt the protective microenvironment of CLL cells in the lymph node, and complementarily reduce MCL-1 levels to enhance sensitivity to venetoclax. Venetoclax was then added. Following venetoclax dose ramp-up, the combination of ibrutinib and venetoclax was given for 12 or 24 cycles or until uMRD was achieved.