HMN 2026: How Chronic leukemia treatment may affect immunity long-term

Treatment with so-called BTK inhibitors has improved the prognosis for people with chronic lymphocytic leukemia (CLL). At the same time, these drugs affect the immune system and may cause side effects over time, according to a new doctoral thesis from Karolinska Institutet.

In recent years, treatment for chronic lymphocytic leukemia has changed with the introduction of drugs known as BTK inhibitors. These are targeted therapies that interfere with signals that leukemia cells need to survive and multiply. The group includes drugs such as ibrutinib, acalabrutinib and zanubrutinib. Treatment can often keep the disease under control for long periods, but it is usually given continuously, making side effects and long-term effects important to understand.

In her doctoral thesis, Maria Andersson, Ph.D. student at the Department of Oncology-Pathology, has investigated how treatment with BTK inhibitors affects people with CLL, with a particular focus on side effects, the immune system and long-term outcomes. The work is based on four studies examining both clinical and biological aspects of treatment.

We asked Andersson to describe her research in more detail.

What are the most important findings?

“We found that side effects such as atrial fibrillation and bleeding are common during long-term treatment with ibrutinib in routine clinical practice, and that side effects are the most common reason for dose reductions or treatment discontinuation.

“We also found that patients treated with BTK inhibitors produced fewer antibodies after repeated COVID-19 vaccinations, while another part of the immune system, the T cells, appeared to be better preserved. At the same time, our analyses showed that treatment affects the immune system over time and that it does not fully return to a normal state.

In addition, we found that some patients were able to take planned breaks from treatment and still respond again when treatment was restarted.”

How can this knowledge help people with chronic lymphocytic leukemia?

“These results may help support a more nuanced and individualized treatment of patients with CLL. By improving our understanding of long-term side effects, reduced vaccine responses and incomplete immune recovery, we may over time become better at monitoring patients, preventing complications and choosing the most appropriate treatment strategy.

The findings also indicate that it is not always sufficient to assess how well the leukemia itself is controlled. We also need to understand how treatment affects the immune system, protection against infections and the patient’s ability to remain on treatment over time. This may in the future contribute to safer and more tailored treatment for people with CLL.”

What are your future ambitions?

“After my thesis defense, I want to continue combining my clinical work as a hematologist with research. In my meetings with patients, questions often arise that I want to understand better, and research provides an opportunity to explore these further. I am particularly interested in clinical studies and would like to work in the future as an investigator and principal investigator.”

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