Genomics, toxicity, and patient preferences represent key considerations for selecting the proper frontline therapeutic regimen for those with chronic lymphocytic leukemia (CLL), according to Talha Munir, MBChB, PhD.
In a conversation with CancerNetwork® at the European Hematology Association (EHA) 2026 Congress, Munir discussed how clinicians should approach the decision between continuous zanubrutinib (Brukinsa), fixed-duration venetoclax (Venclexta)-based therapy, or other agents in the frontline management of CLL. He spoke about these strategies in the context of a matching-adjusted indirect comparison (MAIC) analysis he presented at the meeting, which showed that zanubrutinib substantially improved progression-free survival compared with ibrutinib (Imbruvica) across different clinical trials.
No single factor, Munir said, should determine clinical decision-making in frontline CLL. A combination of elements, ranging from genomic markers like IGHV mutations to the presence of cardiac or infectious toxicities, may ultimately help clinicians and patients decide on treatment.
Munir is a consultant hematologist at Leeds Teaching Hospitals NHS Trust in the United Kingdom (UK) and the deputy chair of the UK National Cancer Research Institute CLL Study Group.
Transcript:
The first thing to say is that the options for [patients with] frontline CLL are a lot at this moment in time. Sometimes, one has to discuss all these options to the patient, so communicating that with our patients has become [fairly important]. What the trial data are showing to us now is that we can use fixed-duration therapy with very good effectiveness for a majority of the patients with frontline CLL, but it also depends on the comorbidity index of the patients and looking at the toxicity profile. All those factors need to be taken into the plan, and not one factor makes a decision for our patients.
For example, [patients with] IGHV-mutated CLL with no infectious comorbidity will benefit from venetoclax or obinutuzumab [Gazyva] therapy, and [they] may benefit from ibrutinib/venetoclax therapy as well. But at the same time, one has to remember that, essentially, these patients also do very well on continuous therapy, and all the data that are being shown at this moment in time is that these frequently are non-inferior data. When you’re deciding therapy, some of this will come down to the genomics of the disease. Sometimes, it will come down to patient preference. Sometimes, it is related to toxicity. For example, for a patient who’s getting a lot of infectious problems, I would not be too keen to give them obinutuzumab as a base therapy. If the patients are having cardiac issues, I would tend not to use a combination of a BTK inhibitor with venetoclax therapy.
These choices are dependent on the genomics, toxicity, and patient preferences. In terms of purely genomics, the [patients with] TP53-mutated [disease] would still benefit from continuous BTK inhibitor therapy, though we need to talk to them about fixed-duration therapy. In [patients without] IGHV mutations, my preference is usually a BTK inhibitor [and] BCL-2 inhibitor combination, and for [patients with] mutations, I usually use venetoclax and obinutuzumab. What we really should not be doing is giving chemoimmunotherapy to our patients.
Reference
Munir T, Jurczak W, Mohseninejad L, et al. Zanubrutinib vs ibrutinib in treatment-naive chronic lymphocytic leukemia (CLL): implications for interpreting fixed-duration treatment outcomes from CLL17. Presented at the European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract PS1718.
