At the 2024 Lymphoma, Leukemia & Myeloma Congress in New York, New York, Alexey Danilov, MD, PhD, City of Hope, Los Angeles, California, participated in a debate of optimal frontline therapies in which he argued in favor of utilizing frontline acalabrutinib for treating patients with chronic lymphocytic leukemia (CLL).

“In sum, I do think acalabrutinib single agent is a very good option for frontline therapy for patients with CLL due to its safety and ease of monitoring,” concluded Dr Danilov.

Transcript:

My name is Alexey Danilov. I'm a professor in the department of hematology and director of the lymphoma center at the City of Hope in Los Angeles, and I'm here at the Lymphoma, Leukemia, [and] Myeloma Congress [2024] in New York City.

I'm participating in a debate which reviews different options for patients with previously untreated chronic lymphocytic leukemia. There are 4 of us debating different sides, including acalabrutinib, which is me, zanubrutinib, venetoclax obinutuzumab, and acalabrutinib obinutuzumab combination. Those are the currently approved frontline therapies for chronic lymphocytic leukemia.

The main question that we often face and discuss with our patients whether to use selective Bruton tyrosine kinase (BTK) inhibitor-based therapies such as acalabrutinib, that I'm debating for, or time-limited therapies such as venetoclax, obinutuzumab, and both each is associated with certain pros and cons.

The different pro factors in favor of acalabrutinib is ease of administration, no reason to monitor for tumor lysis syndrome, very low frequency of follow-up visits and overall safety of this compound, which has now been approved for many years in therapy of CLL and has a fairly long follow-up demonstrating very high efficacy in general CLL population and patients with deletion 17P and in particular, in patients with deletion 17P, acalabrutinib is associated with high efficacy compared with time-limited therapy, which we know is only has about 4-year median progression-free survival.

There are certainly some side effects that we see with BTK inhibitors, both acalabrutinib and zanubrutinib, and that includes hypertension, although acalabrutinib seems to have less of that over time without a direct comparison in existence. This is all indirect, but also atrial fibrillation, which can happen with both drugs. It is for sure very difficult to advocate for acalabrutinib or zanubrutinib when you choose a selective BTK inhibitor just simply due to absence of a clinical trial, which compared the 2.

There's been some minimum inhibitory concentration (MIC) analysis performed in direct comparison analysis, but I would say that those need to be taken with a grain of salt, and I cannot really draw any practice change in conclusions based on that.

In sum, I do think acalabrutinib single agent is a very good option for frontline therapy for patients with CLL due to its safety and ease of monitoring.

Source:

Danilov A. Debate: CLL: Debating Therapeutic Strategies. Presented at Lymphoma, Leukemia & Myeloma Congress; October 16-19, 2024. New York, NY.