Zanubrutinib, Obinutuzumab and Lenalidomide in Newly Diagnosed Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL)

Prior treatment

• (7) Patients who have undergone a major surgical procedure (excluding lymph node biopsy) within the last 14 days or who require a major surgical procedure in anticipation of treatment;
• (9) Requires treatment with potent cytochrome P450 (CYP) 3A inhibitors;

Other illness

• (1) Malignancies other than CLL/SLL (including active CNS lymphoma) have been diagnosed or treated within the past year;
• (4) Other serious medical disorders that would interfere with the study (e.g., uncontrolled diabetes mellitus, gastric ulcers, grade 3 or 4 atrial fibrillation or persistent atrial fibrillation of any grade, other serious cardiorespiratory diseases, etc.). The judgmental decision is vested in the investigator;
• (5) Patient who had infected with Human Immunodeficiency Virus (HIV) or active Hepatitis B Virus (HBV) infection, or any uncontrolled active systemic infection requiring intravenous antibiotics;
• (8) Inability to swallow capsules or suffering from malabsorption syndromes, disorders significantly affecting gastrointestinal function, having undergone gastric or small bowel resection, symptomatic inflammatory bowel disease or ulcerative colitis, and partial or complete intestinal obstruction.
• (12) Persistent uncontrolled bleeding;
• (13) History of life-threatening hemorrhage, especially from irreversible causes;
• (16) Patients with severe hypersensitivity to the active ingredient of the study drug or to any of its excipients;

Lab values

• (3) Non-lymphoma-related hepatic and renal impairment: alanine aminotransferase (ALT) \> 3 times the upper limit of normal, alanine transaminase (AST) \> 3 times the upper limit of normal, total bilirubin (TBIL) \> 2 times the upper limit of normal, and serum creatinine clearance \< 30 ml/min;
• (11) Patients with clinically significant cardiovascular abnormalities (New York Heart Association (NYHA) classification: III/IV), myocardial infarction within 6 months prior to enrollment, malignant arrhythmias (including QTC ≥ 480 ms), poorly controlled blood pressure (systolic ≥ 150 mmHg, diastolic ≥ 100 mmHg) despite the use of antihypertensive medications, and uncontrolled angina;

Age

• (10) Pregnant or lactating women of childbearing age who are not using contraception;

Other

• Patients who met any of the following criteria were excluded from the study:
• (2) There has been clinical evidence of Richter transformation;
• (6) Clinically manifested CNS dysfunction or invasion of the center;
• (14) Need for high doses of several anticoagulants that cannot be briefly discontinued;
• (15) Thrombotic events within three months of treatment initiation;

• 1） Patients were not categorized by gender ，Age ≥18;
• 2） Confirmed diagnosis of CLL or SLL;
• 3）Patients must be untreated, or not undergoing standardized treatment for the first time, under the following conditions:
• a) Not treated with fludarabine-containing or bendamustine-containing or rituximab-containing regimens;
• b) Have not been treated with the application of chlorambucil, or have applied chlorambucil for less than 4 weeks (alone or in combination with adrenal glucocorticoids);
• (c) If the above treatment has been applied, it must be stopped for 2 weeks before enrollment in the group to start the treatment.
• 4） Indications for treatment of CLL/SLL include, inter alia (at least one of the following conditions is met)
  • Evidence of progressive bone marrow failure: as evidenced by progressive decrease in hemoglobin and/or platelets;
  • Giant spleen (e.g., \>6 cm below the left costal margin) or symptomatic splenomegaly;
  • Giant lymph node enlargement (e.g., longest diameter \>10 cm) or symptomatic lymph node enlargement;
  • Progressive lymphocytosis, e.g., \>50% lymphocytosis within 2 months, or lymphocyte doubling time (LDT) \<6 months. When initial lymphocytes are \<30 x 10\^9/L, LDT alone cannot be used as a therapeutic indication;
  • CLL/SLL resulting in symptomatic organ dysfunction (e.g., skin, kidney, lung, spine, etc.)
  • Autoimmune hemolytic anemia (AIHA) and/or immune thrombocytopenia (ITP) that does not respond well to corticosteroids or other standard therapy;
  • Presence of at least one of the following disease-related symptoms: i) weight loss ≥10% without apparent cause within the previous 6 months; ii) severe fatigue (e.g., ECOG physical status ≥2; inability to perform routine activities); iii) temperature \>38°C for ≥2 weeks without evidence of infection; iv) nocturnal night sweats for \>1 month without evidence of infection;
• 5） ECOG≤2
• 6\) Major organ function within 7 days prior to treatment, meet the following criteria: routine blood test criteria: platelets ≥30×10\^9/L; biochemical tests need to meet the following criteria: total bilirubin (TBIL) ≤1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase AST ≤2.5 ULN; creatinine clearance ≥ 30 ml/min; and cardiac Doppler ultrasound assessment: left ventricular ejection fraction (LVEF) ≥ low limit of normal (50%);
• 7\) Male and female patients of childbearing age agree to use reliable contraception throughout the study period and for 4 weeks after the end of study treatment;
• 8\) Patients need to have an expected survival of ≥ 6 months;
• 9\) Patients need to voluntarily participate in this study by signing an informed consent form.