At Karolinska Institutet in Stockholm, Maria Andersson spent years combing through the medical records and blood work of chronic lymphocytic leukemia patients treated with BTK inhibitors—drugs like ibrutinib, acalabrutinib, and zanubrutinib that have transformed outcomes for thousands of people worldwide. What she found was encouraging and complicated in equal measure: these targeted therapies keep the cancer under control for long periods, but they reshape the immune system in ways that don't fully bounce back, even as patients benefit from the treatment itself.
BTK inhibitors represent a watershed moment in CLL treatment. Rather than poisoning the whole body, these drugs interfere with specific signals that leukemia cells need to survive and multiply. They work well enough that many patients can skip chemotherapy's devastating side effects. But because treatment is usually continuous—sometimes indefinitely—understanding what these drugs do to the immune system matters profoundly.
Andersson's doctoral thesis examined four studies spanning both clinical and biological aspects of treatment. The results painted a nuanced picture. Side effects like atrial fibrillation and bleeding are common during long-term ibrutinib use in real-world clinical practice, and these complications are the most frequent reason patients reduce doses or stop treatment altogether. That's important information for people making decisions about their own care.
The immune system findings were particularly striking. Patients treated with BTK inhibitors produced fewer antibodies after repeated COVID-19 vaccinations—a concerning sign for protection against infection. Yet other parts of the immune system told a different story: T cells, another crucial component of immunity, were better preserved than expected. The fuller picture, however, was sobering. Treatment affects the immune system over time, and it does not fully return to a normal state, even after the drugs are stopped.
Not everything was troubling. Some patients were able to take planned breaks from treatment and still respond again when therapy was restarted—a finding that opens possibilities for reducing long-term exposure to side effects.
For doctors and patients navigating CLL together, Andersson's work suggests a path forward that's neither one-size-fits-all nor overly cautious. By understanding long-term side effects, vaccine responses, and incomplete immune recovery, clinicians can monitor patients more carefully, prevent complications, and choose treatment strategies tailored to individual circumstances. The emerging message is that controlling the leukemia itself is only part of the equation. Equally important is how treatment affects infection risk, a patient's ability to stay on medication, and quality of life over years or decades.
Andersson, who continues working as a hematologist while conducting research, is pursuing questions born directly from her encounters with patients. Those conversations—where people ask about what happens to their bodies under long-term treatment—are now informing the next phase of her work. She hopes to lead clinical studies that push this personalized approach further, turning clinical questions into evidence that helps the next generation of CLL patients make informed choices about their own care.