Clinical Pearls for Treating Patients With Newly Diagnosed CLL


An expert hematologist-oncologist offers advice for community oncologists who are treating patients with newly diagnosed chronic lymphocytic leukemia.

Case: A 72-Year-Old Woman with Newly Diagnosed Chronic Lymphocytic Leukemia (CLL)

  • Patient KM is a 72 y/o woman.
    • PMH: Hypertension (well controlled on medication)
    • SMH: Does not smoke; drinks occasional glass of wine in social setting; Walks with friends 2-3 times weekly.

Clinical Presentation:

  • In October 2022, KM visited her PCP for her annual checkup. She reported having persistent fatigue and recent occurrences of night sweats.

Clinical Workup and Diagnosis:

  • WBC: 186,000; 80% lymphocytes
  • Hgb, 9.4 g/dL
  • Platelets, 85 x 109/L
  • ECOG PS 0
  • Elevated serum beta-2-microglobulin
  • Flow cytometry, CD5+, CD20+, CD23+
  • TP53 mutation status – unmutated; IGHV mutation status – unmutated
  • Bone marrow biopsy confirms diagnosis of chronic lymphocytic leukemia (CLL)

Current Treatment:

  • After discussions with her family and clinical team, KM was initiated on fixed duration of venetoclax + obinutuzumab.
    • KM was started on obinutuzumab at 100 mg IV Day 1, followed by 900 mg IV on Day 2, then 1000 mg IV on Days 8 and 15 of Cycle 1; Currently infused with 1000 mg IV on Day 1 of remaining cycles.
    • She was initiated on a ramp-up dosing schedule of venetoclax starting on C1D22 and currently taking the recommended dose of 400 mg PO daily.


John Allan, MD: For community oncologists who are managing and treating newly diagnosed CLL [chronic lymphocytic leukemia], it’s important to understand the biology of the disease. That’s simply done by getting these 3 big categories of tests. [The first is] the FISH [fluorescence in situ hybridization] assay, but I also get a karyotype of the peripheral blood, so you can assess for complex karyotype. [Then there is] next-generation sequencing. We have large panels nowadays that we can send off. We can sequence 200, 300, 400 genes, of which only 4 or 5 are well-validated independent predictors of time to first treatment or poor responses to chemoimmunotherapy. Very few of them have been identified as predictors for poor outcomes on targeted agents. Regardless, when I get this information, I manage my patient differently while I’m in a period of observation. If they have high-risk features, I don’t let them get away from me too far, or let the disease get so advanced that other things can start to happen.

Obviously, the last component is the IGHV-mutational analysis. There’s a lot of nuance there. Sometimes you can identify very low-risk disease, like a V4-34, which usually is a very indolent CLL. You can reassure patients. There are other higher-risk V genes being used, like 4-39, which can associate with Richter [transformation] and NOTCH1 mutations. Another V gene, 3-21, is mutated, stereotyped, and associated with SF3B1 mutations and is a very aggressive high-risk CLL. Identifying all these risk factors is important. You manage your patient differently, and you set expectations differently. Steer away from chemoimmunotherapy if you’re still using that in your practice for these particular high-risk patients. If you know all this information, you’ll be able to provide the most optimal care for your patient.

Transcript edited for clarity.

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