Breaking New Ground: The Promise of Nemtabrutinib in Treating Relapsed Follicular Lymphoma

Bruton tyrosine kinase (BTK) inhibitors are a type of medicine that can treat follicular lymphoma by targeting and eliminating cancerous B cells. They bind to the BTK protein on the surface of the lymphoma cells, which is essential for their growth and survival. This prevents the abnormal B cells from multiplying and spreading, which stops cancer growth. Read more about BTK inhibitors for follicular lymphoma.

BTK inhibitors have proven effective in patients whose disease has stopped responding to treatment or returns after some time in remission. At the latest American Society of Hematology (ASH) congress, new data was presented on nemtabrutinib (MK-1026, Merck Sharp & Dohme), a novel BTK inhibitor.

What We Know About Nemtabrutinib

Nemtabrutinib is an orally available inhibitor of Bruton's tyrosine kinase (BTK) that is effective against malignant B cells that overexpress BTK. It is a once-daily, potent, non-covalent, reversible inhibitor of BTK that can also bind to other B-cell receptor-relevant kinases, potentially increasing its potency against lymphoma cells.

Nemtabrutinib is being studied for several types of lymphoma and chronic lymphocytic leukemia (CLL). Here, we will review the latest information about its potential as a treatment for follicular lymphoma from the Phase 2 BELLWAVE-003 (NCT04728893) study.

The BELLWAVE-003 Study

This study aimed to assess if nemtabrutinib is safe and works against follicular lymphoma cells and other types of blood cancer, including leukemia. This was studied in terms of the number of patients who responded to treatment, for how long, and whether patients lived longer after receiving nemtabrutinib. In this article, we’ll review the results only in patients with follicular lymphoma.

Although Early, Efficacy Results Look Promising 

This study included 36 patients, with a median age of 58, who had previously received chemoimmunotherapy treatment. The great majority had also been treated with lenalidomide. Once enrolled in the study, they received 65 mg of nemtabrutinib once daily for as long as they were benefiting from it.

Some patients are still on therapy, but after six months since the study started, 41% of them have responded to nemtabrutinib, including two patients who have been on treatment for 10 months. However, 20 patients have already left the study due to side effects or the progression of the disease.

It’s too early to draw any conclusions about survival benefits, but 6 months after the study started, all patients were still alive.

Side Effects Experienced Were Expected and Manageable

Investigators highlighted that the most common side effect was a decrease in white blood cells (neutrophils), which was observed in 25% of patients treated. However, the overall safety of nemtabrutinib was as expected from previous studies.

Other key findings regarding side effects were: 

• Despite most patients (86%) experiencing some sort of side effect, just 1 had to modify the dosing, and 3 discontinued the study

• No patients died due to side effects

• In addition to low neutrophil counts, 19% of patients had a decreased number of platelets, and 8% had low red blood cells (anemia)

• No atrial fibrillation or other arrhythmia was observed

Conclusion

“Nemtabrutinib demonstrated promising antitumor activity in a heavily refractory population of patients with FL post chemoimmunotherapy and immunomodulatory therapy”, shared Dr. Wojciech Jurczak from Maria Sklodowska-Curie National Research Institute of Oncology in Poland.

This study is ongoing and still enrolling participants. If you want to explore this and other clinical trials currently looking for patients with follicular lymphoma, you can check our Clinical Trial Finder below:

Clinical Trials for Follicular Lymphoma Patients

Source: 

• Nemtabrutinib, a Noncovalent Reversible BTK Inhibitor in Relapsed or Refractory Follicular Lymphoma: Results from the Phase 2 Bellwave-003 Study