Chronic Lymphocytic Leukemia: Emilia-Romagna at the forefront with new targeted therapies

Chronic lymphocytic leukemia is the most common form of leukemia: it represents about 30% of all diagnoses. In Europe it affects almost 5 people out of 100,000 each year and, in Italy alone, in 2024, approximately 2,750 new cases are estimated. In Emilia-Romagna, we are talking about 185 diagnoses per year.

A chronic disease

It often manifests itself with symptoms such as tiredness, fever, swollen lymph nodes, anemia or a decrease in platelets, but it can also have a much more subtle impact, eroding the quality of life, especially in the elderly, who often also suffer from other pathologies. The disease has a chronic course: after an initial treatment, it can return. This is why it is essential to be able to count on effective therapies over time. Today, research offers new perspectives thanks to the European Commission's approval of Pirtobrutinib, a targeted therapy for adults with chronic lymphocytic leukemia already treated with a Btk inhibitor.

What happens in the body

“Chronic lymphocytic leukemia is a disease in which B lymphocytes grow uncontrollably in the blood, bone marrow and lymphatic tissues,” explains Professor Antonio Cuneo , Director of Hematology at the Ferrara University Hospital. “This increase reduces the space for healthy cells: red blood cells, white blood cells and platelets. This causes anemia and clotting problems, with bruising and bleeding in the most serious cases.”

An often casual diagnosis

Often the diagnosis comes unexpectedly, after routine checks or due to the appearance of swollen lymph nodes in the neck, armpits or groin. “In many cases the disease remains stable for years, without requiring immediate treatment. In these situations we adopt the 'watch and wait' strategy, that is, observing carefully and intervening only when symptoms appear,” adds Cuneo. Treatment begins when the lymph nodes or spleen increase significantly in size, or when hemoglobin or platelets decrease, with symptoms such as extreme tiredness or bleeding. This is why regular checkups are so important.

Increasingly personalized therapies

"In some patients the disease presents itself in a more aggressive form," Cuneo explains, "but management has improved a lot in recent years thanks to new treatments and greater personalization of care. Chemotherapy today, except in special cases, is no longer the first choice: biological therapies are more effective and better tolerated, without some of the more severe toxicities of the past, such as prolonged immunosuppression or the appearance of other tumors."

New perspectives

Having innovative drugs such as covalent Btk or Bcl-2 inhibitors has changed patients' lives. "Even those who need timely treatment can now lead a normal life," says Cuneo, "thanks to targeted therapies, to be performed in specialized centers such as those in Emilia-Romagna." Among these, Pirtobrutinib represents an important innovation: it is a non-covalent Btk inhibitor capable of recovering the response in patients who have already been treated, keeping the disease under control for a long time. In the Bruin CLL-321 study, it reduced the risk of progression or death by 46%, with an average time to the next treatment of about two years. "Pirtobrutinib is a therapy that fills an important gap for those who no longer respond to covalent Btk inhibitors," continues Cuneo. "Its targeted and selective mechanism of action allows us to overcome resistance and offer a new therapeutic opportunity."

The results of the clinical study

The European approval is based on data from the Bruin CLL-321 study, the first randomized Phase 3 study conducted exclusively in patients previously treated with a Btk inhibitor. Pirtobrutinib was shown to be superior to two comparator options: idelalisib + rituximab and bendamustine + rituximab. It prolonged progression-free survival (median PFS: 14 vs. 8.7 months), with benefits also confirmed in patients with high-risk mutations (TP53, 17p deletion, unmutated IGHV).

Improvements in control duration

In addition, the median time to subsequent treatment or death was 24 months versus 11 months in the control group, a 63% improvement. The safety profile was consistent with that observed in previous studies. The most common side effects were neutropenia, fatigue, diarrhea, anemia, rash, and bruising.

A new therapeutic horizon

“This new indication represents a real opportunity for patients who until now had few alternatives – comments Elias Khalil , General Manager of the Lilly Italy Hub –. We are committed to making this therapy available as quickly as possible to offer new solutions to patients with blood cancers”. Pirtobrutinib has already received a conditional marketing authorization for relapsed or refractory mantle cell lymphoma and applications are underway to extend the indications to other types of tumors worldwide.