Expert Andrew Lipsky, MD, reviews a patient case of relapsed/refractory chronic lymphocytic leukemia managed with BTK inhibition in the second-line setting.
Andrew H. Lipsky, MD: Hi, I’m Andrew Lipsky. I’m an assistant professor of medicine at Columbia University [in New York, New York]. It’s my pleasure to be with you for this Targeted Oncology™ Case-Based Peer Perspectives. I’ll be discussing the case of a 72-year-old man with relapsed/refractory chronic lymphocytic leukemia [CLL]. We have a 72-year-old man who presented initially with an asymptomatic lymphocytosis that was identified 4 years ago. Initially he was monitored, and after 2 years he developed anemia, night sweats, and splenomegaly. The diagnosis of chronic lymphocytic leukemia was made, and the decision was made to pursue first-line treatment with venetoclax and obinutuzumab.
Thirteen months after completing therapy, the patient was ECOG 1. He developed palpable splenomegaly and had a recurrence of lymphadenopathy. The largest lymph node was 4.2 cm x 2.8 cm. When looking at his comorbidities, it was notable for a history of coronary artery disease. He also had a high cardiovascular risk due to having a NSTEMI [non-ST-elevation myocardial infarction] treated with stents. For his medications, he’s on a statin, takes amlodipine, and is on aspirin and Plavix (clopidogrel).
When we worked up his CLL, he had leukocytosis with a white blood cell count of 34,000 per mm3 and an absolute lymphocyte count of 21,000 per μL. He’s anemic, with a hemoglobin of 9.3 g/dL, and thrombocytopenic with platelets of 78 per mm3. When sending his CLL prognostic studies, he now has a complex karyotype with 4 specific abnormalities on CLL karyotype. His FISH [fluorescence in situ hybridization] shows the presence of a deletion 11q without a deletion 17p. His IGHV, which was checked initially, was unmutated. Upon repeat testing for TP53 aberrancy, he now has an unmutated TP53. His largest lymph node is 4.2 cm. On the basis of recurrent lymphadenopathy and recurrent anemia, the decision was made to start treatment with a BTK [Bruton tyrosine kinase] inhibitor. He was initiated on zanubrutinib.
This is a patient who [received] the CLL14 [trial] regimen in the first line. That’s the combination of venetoclax and obinutuzumab. The patient was presumably treated with a good initial response to that regimen but now has disease relapse. Disease relapse is evident from rising lymphocytosis, new anemia, and new lymph nodes on physical exam. This can often be seen after the CLL14 regimen.
What’s particularly interesting about this case is that the patient got only 13 months of the regimen after completing treatment. The 5-year PFS [progression-free survival] for the CLL14 regimen is around 62%. This patient is clearly in need of additional therapy for symptomatic CLL, and the option to re-treat with venetoclax sometimes could be considered in someone who got a lot of mileage out of it. This isn’t that much mileage, so the decision to treat with a BTK inhibitor is absolutely reasonable. We know from the ALPINE study that relapsed/refractory patients treated with zanubrutinib can have excellent outcomes and even superior outcomes when it comes to progression-free survival vs a first-generation BTK inhibitor like ibrutinib.
All CLL is addicted to the B-cell receptor activation pathway, and BTK is a proximal kinase in that pathway. Inhibition of that kinase blocks the signal from getting to the nucleus that results in survival of the CLL cell and the prevention of apoptosis. It’s a potent strategy to turn off that initial signal that the CLL cell is addicted to.
Transcript edited for clarity.