Strategies to avoid adverse events (AEs) with novel therapies include the use of time-limited venetoclax-based regimens and second-generation Bruton tyrosine kinase (BTK) inhibitors, which have a lower risk of certain AEs (eg, atrial fibrillation, bleeding, and hypertension). However, when I consider the serious toxicities associated with the use of BTK inhibitors that can result in a patient discontinuing treatment, I think that it is also important to make our patients with CLL aware of the less serious—albeit annoying—toxicities, including arthralgia, diarrhea, mouth sores, and cramps that are never grade 3/4 in severity but are nevertheless bothersome to patients.

It is important to support patients by letting them know that the side effects that they are experiencing will usually dissipate over the first few months of treatment and by encouraging them to stick it out. For example, if a patient with CLL develops mouth sores that cause pain when eating or drinking, they may consider discontinuing treatment, given the prospect of a long-term side-effect burden. It is rewarding when a patient appreciates your counseling about the transient nature of AEs, and this support helps get them through the first few months of treatment.

Dose reduction can also be useful in patients with CLL who develop toxicities, and that is my first inclination, rather than changing drugs; however, dose reduction does not work in every patient. There are some patients in whom I have reduced their doses and there was no question that the frequency of that side effect decreased, and then there are others in whom the dose reduction did not make a difference. Also, there is no established threshold dose below which you will not see a particular side effect. Dose reduction is less common these days, with the availability of alternative agents in the same class. I think that more people are likely to say something like, “Let’s just switch over to another agent.” In my experience, the majority of patients who discontinued ibrutinib for toxicity, for example, were able to tolerate acalabrutinib. While dose reduction is an option that I use, I suspect that it is probably easier for many physicians to just shift treatments because of the availability of acalabrutinib. But, certainly, dose reduction is tried and true.