Dr Jurczak on the Role of Nemtabrutinib in R/R Follicular Lymphoma Management

“We think that nemtabrutinib [could be an] alternative therapeutic option in a heavily pretreated follicular lymphoma population. It’s a very [interesting] compound to be combined with other drugs, regarding its low [rate of associated] toxicity and excellent [tolerability profile].”

Wojciech Jurczak, MD, PhD, hematologist/oncologist, head, Department of Clinical Oncology, Maria Skłodowska-Curie Institute of Oncology, discusses the role of nemtabrutinib (ARQ-53), a noncovalent, reversible BTK inhibitor, in the treatment of patients with relapsed or refractory follicular lymphoma. These insights were presented at the 2024 ASH Annual Meeting.

Jurczak highlights that in the phase 2 BELLWAVE-003 trial (NCT04728893), nemtabrutinib demonstrated promising antitumor activity in this heavily pretreated population, with an objective response rate of 41% (95% CI, 24%-61%), including 1 complete response and 11 partial responses. He notes that 21% of patients achieved stable disease. The median duration of response was 5.8 months (95% CI, 1.5-not reached [NR]), and most patients experienced marked reductions in tumor volume, according to Jurczak.

Survival outcomes from BELLWAVE-003 further underscore nemtabrutinib’s potential, Jurczak continues. The median progression-free survival was 5.5 months (95% CI, 2.8-NR), with 34% of patients progression free at 6 months. Although the median overall survival (OS) was NR (95% CI, 10.4 months-NR), the 6-month OS rate was 100%. These findings indicate durable clinical benefit with nemtabrutinib in this population, despite the advanced disease status of the enrolled patients, Jurczak says.

The safety profile of nemtabrutinib was consistent with previous data on BTK inhibitors, Jurczak shares. Treatment-related adverse effects (TRAEs) were reported in 69% of patients, with grade 3/4 TRAEs occurring in 31% of patients. Common AEs with the investigational agent included neutropenia (25%), anemia (19%), and constipation (11%). He emphasizes that these AEs were manageable, and dose reductions or discontinuations due to AEs were infrequent.

Jurczak highlights that nemtabrutinib’s manageable toxicity profile and reversible mechanism of action make it a viable therapeutic option for patients with follicular lymphoma who have exhausted other treatment options. He notes that its favorable safety profile positions it as a potential candidate for combination regimens in future studies.

Ongoing research is exploring how nemtabrutinib can be integrated into treatment strategies for follicular lymphoma, Jurczak concludes. He stresses the need for further investigations to confirm its efficacy and to evaluate its utility in combination with other therapies to improve patient outcomes in this challenging disease setting.