Abstract: Disclosed herein are methods and combination dosing regimen of administering a combination of a BTK inhibitor (e.g. ibrutinib) and an anti-CD20 therapeutic agent for the treatment of a hematologic malignancy. In one aspect is a combination dosing regimen for the treatment of a hematologic malignancy in a subject in need thereof comprising a first phase and a second phase, wherein the first phase is an administration of a BTK inhibitor as a single-agent treatment for a first extended period of time, and the second phase is an administration of a combination of the BTK inhibitor and an anti-CD20 therapeutic agent for a second extended period of time. In one embodiment, the first extended period of time is a period of up to 90 days.