Risk Stratification for Newly Diagnosed Chronic Lymphocytic Leukemia

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

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

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: In general, this is a routine type of case. [The patient] is not necessarily extensively high risk by some of the features that we now believe to be high risk in the era of targeted agents, but is somewhat in an intermediate-risk group. When you look at the CLL-IPI [Chronic Lymphocytic Leukemia-International Prognostic Index], which is something you can calculate to assess risk for a patient and is best validated in the era of chemoimmunotherapy, she technically does meet the criteria for high risk. CLL-IPI is a group of 5 risk factors, that being age, Rai stage, beta-2 microglobulin, IGHV mutational status, and TP53 disruption. It’s a weighted-based scoring system, with age and Rai stage giving 1 point, beta-2 microglobulin and IGHV mutational status each giving 2 points, age greater than 65, and then TP53 disruption giving you 4 points. So anywhere from 0 to 10 assesses for risk, and anywhere from 4 to 7 is high risk, from 8 to 10 is very high risk, and anything below that is intermediate, and low if you have 0 to 1 point, etc.

This patient, technically, by having an unmutated IGHV, elevated beta-2 microglobulin, age greater than 65, and having Rai stage IV disease by platelets less than 100,000 per microliter meets the criteria for high-risk disease, with a CLL-IPI of 6. There’s another scoring system called the CLL4, which technically we wouldn’t be able to calculate because we don’t have all the information on this patient. It’s made up of 4 different factors and maybe is the better gauge of risk in the era of targeted agents. That’s assessed by LDH [lactate dehydrogenase], which we didn’t have for this patient, and if it is elevated, you get a point. With a severely elevated beta-2 microglobulin, which we weren’t provided in this case, but greater than 5, you get a point. And having TP53 disruption, you have a point. Then if you have relapsed disease, you get a point. So anywhere from 0 to 4 is how that scoring system works.

They don’t crosstalk very well honestly, the high-risk patients identified by CLL-IPI are not identified by the CLL4. Our scoring systems in CLL need to be improved and need to be better. But in a sense, if you’re thinking about assessing this and calculating it for your patient, it’s best to use it for time to first treatment. That’s how I use it when I think about it. But as you’re using targeted agents, the CLL-IPI is not very good at identifying the patient. Ultimately, I think this patient is in this intermediate- to high-risk group, and targeted agents are the favored approach in the United States, and my favorite approach. I don’t use chemoimmunotherapy for this patient. She’s otherwise very fit. I think straight BTK [Bruton tyrosine kinase] inhibitor continuous therapy treatments, of which we have 3, vs a fixed-duration approach with venetoclax and obinutuzumab are very reasonable options.

Given the fact that she’s very fit, she’s not on a lot of medications, she’s maybe traveling a bunch and doesn’t want to be on treatment for a long period of time, I do think this treatment approach is completely reasonable. There are great data in this patient population for that based on the CLL14 study, which was looking at venetoclax and obinutuzumab vs chlorambucil and obinutuzumab in patients older than 65. So there’s great evidence for this, and I think it’s a great option and approach for this specific patient, despite the fact that she has some higher-risk disease features.

Transcript edited for clarity.