Venetoclax as Consolidation in CLL Patients Treated With BTK Inhibitor Monotherapy

Inclusion Criteria: * 1\. Age: 18-80 years-old. * 2\. Patients must have a diagnosis of CLL/SLL. * 3\. Detectable MRD by flow cytometry (10\^-4 sensitivity) in the peripheral blood. * 4\. Patients who are on BTK inhibitor monotherapy for more than 6 months. This study includes patients who are taking one of the following BTK inhibitors: ibrutinib, zanubrutinib, orelabrutinib, and acalabrutinib. * 5\. Patients need to have a response of at least PR (CR/PR) to BTK inhibitor monotherapy. * 6\. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2. * 7\. Patients must have adequate renal and hepatic function: * Serum bilirubin ≤ 1.5 × upper limit of normal (ULN) or ≤ 3 × ULN for patients with Gilbert's disease; * Serum creatinine clearance of ≥ 50 ml/min (calculated or measured); * ALT and AST ≤ 3.0 × ULN, unless clearly due to disease involvement. * 8\. Adequate bone marrow function: * Platelet count of greater than 50,000/µl, with no platelet transfusion in prior 2 weeks; * ANC ≥ 1000/µl in the absence of growth factor support unless due to compromised bone marrow production from CLL, indicated by ≥ 80% CLL in marrow; * Hemoglobin ≥ 8g/dL. * 9\. Adequate cardiac function, as assessed by: * Absence of uncontrolled cardiac arrhythmia; * Echocardiogram demonstrating LVEF ≥ 35%; * NYHA functional class ≤ 2. * 10\. Ability to provide informed consent and adhere to the required follow-up. Exclusion Criteria: * 1\. Richter transformation. * 2\. Active malignancy requiring systemic therapy, other than CLL, with the exception of: adequately treated in situ carcinoma of the cervix uteri; adequately treated basal cell carcinoma or localized squamous cell carcinoma of the skin; previous malignancy confined and surgically resected (or treated with other modalities) with curative intent. * 3\. Major surgery, radiotherapy, chemotherapy, biologic therapy, immunotherapy, experimental therapy within 3 weeks prior to the first dose of the study drug. * 4\. Grade 3 or 4 hemorrhage within the past 3 weeks. * 5\. Uncontrolled active infections (viral, bacterial, and fungal). * 6\. Females who are pregnant or lactating. * 7\. Known HIV positive. * 8\. Active hepatitis B infection (defined as the presence of detectable HBV DNA or HBe antigen). Patients who are HBsAg positive or HBcAb positive are eligible, provided HBV DNA is negative. These patients must have monthly monitoring of HBV DNA for the duration of the study. * 9\. Active hepatitis C, defined by the detection of hepatitis C RNA in plasma by PCR. * 10\. Active, uncontrolled autoimmune phenomenon (autoimmune hemolytic anemia or immune thrombocytopenia) requiring steroid therapy \> 20 mg prednisone daily or equivalent, within 7 days of starting venetoclax. * 11\. Received other therapeutic agents for CLL/SLL during BTK inhibitor treatment prior to enrollment. * 12\. Concurrent use of warfarin or equivalent vitamin K inhibitor or other oral anticoagulant treatment. * 13\. Received strong CYP3A inhibitors or strong CYP3A inducers within 7 days of starting venetoclax. * 14\. Consuming grapefruit, grapefruit products, Seville oranges, or star fruit within 7 days of starting venetoclax. * 15\. Prior treatment with venetoclax or other Bcl-2 inhibitor. * 16\. Malabsorption syndrome or other condition that precludes enteral route of administration.