Frontline Treatment Approaches for Patients With Newly Diagnosed CLL

EP: 1.Case Overview: A 72-Year-Old Woman with Newly Diagnosed Chronic Lymphocytic Leukemia

EP: 2.Risk Stratification for Newly Diagnosed Chronic Lymphocytic Leukemia

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EP: 3.Frontline Treatment Approaches for Patients With Newly Diagnosed CLL

EP: 4.CLL14: Venetoclax and Obinutuzumab in Patients With Previously Untreated CLL

EP: 5.CLL Treatment: Managing Adverse Events With Venetoclax and Obinutuzumab

EP: 6.Recent Data from BTK Inhibitor Studies in CLL

EP: 7.Managing Disease Recurrence in CLL

EP: 8.Clinical Pearls for Treating Patients With Newly Diagnosed CLL

EP: 9.Treatment Research Landscape in 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.

Transcript:

John Allan, MD: There are several frontline treatment approaches in newly diagnosed CLL [chronic lymphocytic leukemia] that are FDA approved. In early 2023, we had some new approvals even for CLL. There are 2 standard approaches per the NCCN [National Comprehensive Cancer Network] guidelines that we think about. The first approach and the oldest, tried-and-true approach is a continuous therapy BTK [Bruton tyrosine kinase] inhibitor approach. BTK inhibitors are a class of drugs that include agents such as ibrutinib, acalabrutinib, and the most recent addition to this FDA approval is zanubrutinib, which achieved FDA approval in CLL in January of 2023. These drugs are all great. Acalabrutinib and zanubrutinib have differentiated themselves in terms of selectivity for BTK and have less off-target effects, therefore potentially fewer toxicities. That has been borne out in head-to-head clinical trials. So in a sense, in the United States the most preferred BTK [inhibitors] are these second-generation agents such as acalabrutinib or zanubrutinib. But ibrutinib is still there and is also a great agent and option.

The other approved frontline option for our patients with CLL is a venetoclax and obinutuzumab-based approach. This has gained approval based on the CLL14 study, as I alluded to. These are the 2 main therapeutic approaches. What we don’t have are head-to-head data between these 2 types of approaches available, though there are ongoing clinical trials accrued that are assessing this question. Right now, we don’t have head-to-head data to say one approach is better or whether a patient population is better for one approach. Obviously, there are pros and cons to a continuous therapy inhibitor-based approach vs a venetoclax fixed-duration–based approach. And we’ll be going through those throughout this session.

Transcript edited for clarity.