What to Consider Before Prescribing a BTK Inhibitor Such as Calquence for CLL Patients

BTK Inhibitors — From Minor Side Effects to Serious Risks

• Second-generation BTK inhibitors such as acalabrutinib (brand name: Calquence) are generally safer than first-generation drugs, but they can still have side effects
• Even less serious side effects could affect patient adherence to treatment
• Bleeding and other more serious adverse effects require careful consideration when prescribing

Bruton kinase (BTK) inhibitors have only emerged in recent years, but already they have become an established therapy for chronic lymphocytic leukemia (CLL) and other hematologic malignancies. Second-generation BTK inhibitors such as acalabrutinib (brand name: Calquence) tend to have a better safety profile than the first-generation drugs, but side effects are still a concern.

Adverse effects typically fall into two categories: less serious but more chronic events such as headaches, hypertension, rash, fatigue, and diarrhea; and less frequent but more concerning side effects such as atrial fibrillation or bleeding.

The first group of side effects, though less serious, can have significant effects on patients’ quality of life and adherence to treatment. “We don’t want patients starting to skip treatment because they are trying to avoid a side effect or decrease the dose, because we know that in BTK inhibitors, intermittent or interrupted treatment can lead to resistance clone selection,” Dr. Sikander Ailawadhi, hematologist-oncologist and professor of medicine at Mayo Clinic in Jacksonville, Fla., tells SurvivorNet Connect.

The higher risk side effects require more careful consideration and a few extra steps — for example avoiding the use of BTK inhibitors with blood thinners such as aspirin and warfarin, and stopping these drugs before surgery to prevent excessive bleeding.

The good news is that any side effects that do occur tend to appear soon after patients start taking the drug. “If an adverse event has not shown up within the first several months, it is less likely that a new adverse event will show up down the road,” Dr. Ailawadhi says.