eCase - BTKi Resistance in CLL

Introduction

In this activity, Matthew S. Davids, MD, MMSc, and Lindsey Roeker, MD, discuss Bruton’s tyrosine kinase (BTK) inhibitor resistance in chronic lymphocytic leukemia (CLL), including optimal testing and treatment sequencing to overcome resistance to prior therapy.

The key points discussed in this module are illustrated with thumbnails from the accompanying downloadable PowerPoint slideset, which can be found here or downloaded by clicking any of the slide thumbnails in the module alongside the expert commentary.

Clinical Care Options plans to measure the educational impact of this activity. Some questions will be asked twice: once at the beginning of the activity and then once again after the discussion that informs the best choice. Your responses will be aggregated for analysis, and your specific responses will not be shared.

Before continuing with this educational activity, please take a moment to answer the following questions.

How many people with CLL do you provide care for in a typical month?

A.
1-4
B.
5-10
C.
11-15
D.
16-20
E.
>20
F.
Not applicable

How often do de novo BTK inhibitor resistance mutations occur in patients with CLL?

A.
Never
B.
Rarely
C.
Sometimes
D.
Often

Based on recent matching-adjusted indirect comparison (MAIC) data from phase III trials, which of the following accurately describes landmark 2- and 3-year progression-free survival (PFS) and hypertension (HTN) rates with acalabrutinib vs zanubrutinib for CLL?

A.
Similar PFS rates and HTN rates
B.
Similar PFS rates and lower HTN rates
C.
Increased PFS rates and HTN rates
D.
Increased PFS rates and lower HTN rates

A 67-year-old male with CLL was treated with FCR 6 years ago and achieved a partial remission. At a follow-up visit, he complained of worsening fatigue; bilateral cervical and axillary lymphadenopathy and new splenomegaly were observed. Testing indicated unmutated IGHV; CLL fluorescence in situ hybridization (FISH) showed del(11q), and no TP53 mutation was noted on next-generation sequencing (NGS) panel. The patient was treated with single-agent acalabrutinib and achieved a partial response. However, 5 years later, he experienced worsening lymphocytosis and relapsed CLL was confirmed. An NGS panel showed a BTK C481S mutation; a TP53 mutation was also noted. The patient began treatment with venetoclax plus rituximab and achieved an excellent response, after which he continued with venetoclax single agent. However, 3 years later, he starts experiencing progressive lymphocytosis; scans confirm progressive lymphadenopathy and splenomegaly.

In your current practice, what would you recommend for this patient?

A.
Add rituximab back to venetoclax monotherapy
B.
Add ibrutinib to venetoclax
C.
Switch to zanubrutinib
D.
Switch to pirtobrutinib
E.
Switch to PI3K inhibitor–based therapy (eg, idelalisib + rituximab)

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A Cancer Conversation: Optimizing the Care of Patients With CLL Through a Deeper Understanding of BTK Inhibitor Resistance

Matthew S Davids, MD, MMSc

Lindsey Roeker, MD

Activity

Introduction

How many people with CLL do you provide care for in a typical month?

How often do de novo BTK inhibitor resistance mutations occur in patients with CLL?

Based on recent matching-adjusted indirect comparison (MAIC) data from phase III trials, which of the following accurately describes landmark 2- and 3-year progression-free survival (PFS) and hypertension (HTN) rates with acalabrutinib vs zanubrutinib for CLL?

In your current practice, what would you recommend for this patient?