A new drug (nemtabrutinib) from the class of BTK inhibitors for the treatment of chronic lymphocytic leukemia (CLL and SLL)

Chronic lymphocytic leukemia (CLL) is a disease affecting a specific subtype of white blood cells (B lymphocytes). CLL is the most common form of leukemia in Western countries. It is closely related to small lymphocytic lymphoma (SLL), so the two conditions are often grouped together. The disease can affect people of various age groups, although the median age of onset is 70 years. Treatment for CLL/SLL is usually not started until patients show symptoms of the disease. Prior to that, CLL can be monitored so that intervention can occur if the condition worsens. Typically, CLL and SLL progress very slowly. The choice of medication depends on the patient’s overall health, other relevant medical conditions, and genetic alterations in the CLL cells. Treatment has evolved; instead of the former standard of chemoimmunotherapy, targeted inhibitors of specific structures on or within the cells are now frequently used. This causes the malignant cells to die in a targeted manner; fortunately, side effects on other cells are usually minimal. This can significantly improve the prognosis for patients. A class of drugs now used as standard therapy are so-called BTK inhibitors (Bruton’s tyrosine kinase inhibitors), which specifically target a structure in the malignant cells, thereby leading to cell death. BTK inhibitors are already being used as first-line therapy.

In the BELLWAVE-011 study, a new drug from the BTK inhibitor class, nemtabrutinib, is being compared with the approved BTK inhibitors ibrutinib and acalabrutinib. Patients are randomly assigned to two groups. In one group, they receive nemtabrutinib, which has so far only been studied in clinical trials; in the other, they receive the current first-line therapy with ibrutinib or acalabrutinib, depending on the choice made by the medical staff. Treatment continues until disease progression or discontinuation due to severe side effects. The effectiveness of the treatment will be evaluated for approximately just under 3 years after the start of therapy. Researchers hope that the new drug, nemtabrutinib, will cause fewer side effects and be at least as effective as ibrutinib or acalabrutinib—or even more effective. Follow-up will continue for approximately 104 months (8.5 years).

Women and men aged 18 and older with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) are eligible to participate in the study if their disease is active and they require treatment for it. Patients must not have received any prior systemic treatment for CLL or SLL and must not have received radiation therapy within 2 weeks prior to the start of the study. In addition, they should be in good physical condition (ECOG 0–2). Certain organ diseases, such as active liver inflammation (viral hepatitis B or C) or HIV, may be grounds for exclusion from the study.