Treating a Patient With Unmutated IGHV, ATM-Deleted Chronic Lymphocytic Leukemia

Talha Munir, MD, St. James's Hospital in Leeds, United Kingdom, highlights his treatment choices for the case of a 76-year-old patient with unmutated IGHV, ATM-deleted chronic lymphocytic leukemia (CLL).

Transcript:

Hi, my name is Dr. Munir. I'm a hematology consultant working at St. James's Hospital in Leeds, UK. We had a discussion about this 76-year-old gentleman who's got binet stage C CLL, as well as rai stage 3 CLL with unmutated IGHV status, as well as ATM gene deletion, in need of treatment. We had various options that were tabulated. 

The one which we'll exclude completely is chemoimmunotherapy, because clearly with unmutated IGHV status and ATM gene deletion, this would be the least preferred option. The treatment option that we chose for this patient, along with discussion with the patient, was venetoclax with obinutuzumab as a fixed-duration therapy for 12 months. 

This patient was very keen to have fixed-duration therapy and in context of the CLL 14 data, it was clear that unmutated IGHV patients had an estimated progression-free survival at 5 years or 55%. Though one can argue that strictly speaking, continuous BTK-inhibitor therapy would be a reasonable option for this patient as well and may improve the outcomes. But it was a discussion with the patient about choosing venetoclax-based therapy as fixed-duration therapy, as well as choosing therapy based on the continuous BTK inhibitor therapy.

The other things to consider in this patient was the history of ischemic heart disease and the need for antiplatelet therapy. Obviously that is not a contraindication to use a BTK inhibitor therapy, but some patients would like, when they consider this combination, to consider how many antiplatelet drugs the patients are taking. And with aspirin, the use of acalabrutinib or ibrutinib may be reasonable.

I think the other therapy to consider was fixed-duration ibrutinib with venetoclax, which is not licensed for use at this moment in time. But we have seen the data coming through from GLOW study and CAPTIVATE study showing that this combination may be quite useful in unmutated IGHV patient as fixed-duration therapy. And some patients appear to be very sensitive with unmutated IGHV status to this combination, although the long-term data is still accumulating.

In terms of the ATM gene deletion, the targeted drugs kind of circumvent the negative impact of ATM gene deletion. I think both combination of venetoclax with obinutuzumab or BTK-inhibited therapy would be sensible in this scenario. Thank you for listening.

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Case Presentation: Treating Unmutated IGHV ATM-Deleted Chronic Lymphocytic Leukemia