Frontline and Subsequent Therapies for Chronic Lymphocytic Leukemia

Choosing BTK Inhibitors Versus Venetoclax as First-Line CLL Therapy

Nilanjan Ghosh, MD, PhD, discusses when a Bruton’s tyrosine kinase inhibitor would be preferred over a BCL-2 inhibitor as first-line therapy for patients with chronic lymphocytic leukemia.

Nilanjan Ghosh, MD, PhD, chief of lymphomas at Atrium Health Levine Cancer Institute, discusses when a Bruton’s tyrosine kinase (BTK) inhibitor would be preferred over a BCL-2 inhibitor as first-line therapy for patients with chronic lymphocytic leukemia (CLL).

The BCL-2 inhibitor venetoclax (Venclexta) plus the anti-CD20 agent obinutuzumab (Gazyva) is a recommended first-line option for patients with CLL, as are the BTK inhibitors ibrutinib (Imbruvica) and acalabrutinib (Calquence) plus obinutuzumab. According to Ghosh, a BTK inhibitor is preferred over venetoclax in patients with a deletion 17p or TP53 mutation due to lower risk of relapse. Venetoclax is administered for a fixed duration of 24 months, while BTK inhibitors can be given indefinitely.

Another concern Ghosh considers for patients receiving venetoclax is the risk of tumor lysis syndrome (TLS), which is mitigated by a 5-week step-up dosing. Older patients, those with renal dysfunction, or those with bulky disease may be at greater risk from TLS. Managing TLS risk may also be difficult for patients who live far from the treatment center.

A head-to-head trial (NCT02477696) showed that acalabrutinib was associated with less cardiotoxicity than ibrutinib, including a 9.4% rate of atrial fibrillation versus 16% with ibrutinib, and fewer discontinuations due to adverse events. Ghosh says this would be a reason to choose acalabrutinib for patients with cardiac comorbidities.

TRANSCRIPTION:

0:08 | So if I'm if I'm thinking of using a BTK inhibitor—acalabrutinib or ibrutinib—over venetoclax and obinutuzumab, that's mainly in [patients with] deletion 17p, or patients with a TP53 mutation, where I may be a little more worried about defined-time duration therapy, and more comfortable using indefinite BTK inhibition.

Also, in patients who have renal dysfunction, they may have problems with the step-up dosing with the venetoclax even though we do the step-up dosing, tumor lysis risk, and problems in patients who have significantly impaired renal function or advanced age, and also for patients who live far from the center, and perhaps who have very bulky disease, that would be very bulky disease would also put them at high risk of TLS with venetoclax, it's still doable, for sure, but it's just a little bit harder. And so, in those patients, I typically prefer using a BTK inhibitor.

And then, in terms of acalabrutinib over ibrutinib, perhaps patients with cardiac comorbidities; there was a head-to-head study showing lower risk of atrial fibrillation with acalabrutinib over ibrutinib. So, if I'm thinking of somebody who has cardiac comorbidities, [acalabrutinib] comes more in terms of a favorable profile in those patients.