Managing CLL Treatment Side Effects
- BTK inhibitors (Bruton tyrosine kinase inhibitors) are generally well-tolerated treatments for chronic lymphocytic leukemia (CLL), with most patients experiencing only mild, manageable side effects such as minor GI issues, skin changes, easy bruising, or a petechial rash.
- “The good news is that they’re extremely well tolerated, and it’s actually pretty rare to see significant side effects in patients,” says Dr. Kieron Dunleavy with MedStar Georgetown University Hospital at the Georgetown Lombardi Comprehensive Cancer Center in Washington, D.C.
- Rare but important risks — including bleeding concerns around surgery, occasional atrial fibrillation, and a modest increase in infections — mean patients should stay in close communication with their care team while on these therapies.
BTK inhibitors work by blocking a BTK enzyme in a signaling pathway that CLL and SLL cells rely on.
Read MoreThe Most Common, Minor Side Effects
Many patients starting a BTK inhibitor experience only minor issues, Dr. Dunleavy says, which can include:- Mild gastrointestinal symptoms
- Skin-related side effects
- Easy bruising
- A skin finding called a petechial rash — tiny red or purple spots that can result from mild abnormalities in platelet function caused by these drugs
Bleeding Risk and Surgery
Since BTK inhibitors can affect platelet function, they can modestly increase the risk of bleeding in some patients. This is an important consideration for anyone who has an upcoming surgery or procedure.
“When you’re on these drugs and if you have to go for surgery, it’s always important to check with your hematologists and oncologists about how long you need to keep off the drug before you have surgery,” Dr. Dunleavy advises.
Care teams generally recommend a temporary pause in treatment around the time of a procedure, and the exact timing should always be determined with your treating physician.
Atrial Fibrillation: A Less Common but Serious Side Effect
One of the more serious side effects linked to BTK inhibitors is atrial fibrillation, an irregular and often rapid heart rhythm. Dr. Dunleavy notes that this side effect occurs only rarely and appears to be becoming less common as the drug class evolves.
“That is a side effect that looks like it’s much more prominent in the early BTK inhibitors,” he explains. “And as the BTK inhibitors advance and we have newer generations of BTK inhibitors, we’re seeing less atrial fibrillation.”
Infection Risk
Like many novel targeted cancer therapies, BTK inhibitors are associated with a modestly increased risk of certain infections, although Dr. Dunleavy notes that serious infections are not common. “We do know that when you’re on these types of agents, just like a lot of the novel therapies that we use, there is a slightly increased risk of getting certain infections,” he says.
Expert Resources for CLL Patients
Two Generations of BTK Inhibitors
The first BTK inhibitor to reach the clinic was ibrutinib (Imbruvica), followed by additional drugs in the same category. These earlier drugs are known as covalent BTK inhibitors, meaning they bind permanently to the BTK enzyme. They remain widely used and highly effective in CLL and SLL.
More recently, a second type of BTK inhibitor — a non-covalent (or reversible) BTK inhibitor — has entered the treatment landscape. The first drug of this type approved for CLL/SLL is pirtobrutinib, sold under the brand name Jaypirca. Since it binds to BTK differently than the covalent drugs, it can remain effective even after a patient’s disease has stopped responding to an earlier-generation BTK inhibitor.
What This Means for Patients
Most people tolerate BTK inhibitors well, and serious complications are the exception rather than the rule. Still, because these drugs can affect the heart, the blood’s clotting ability, and infection risk, ongoing monitoring — including regular blood counts and check-ins with your care team — is an important part of staying on these therapies safely.
Patients should always report new or unusual symptoms, including irregular heartbeat, unusual bruising or bleeding, or signs of infection, to their oncology team promptly.
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