Dr Nowakowski on the Significance of the TakeAim Lymphoma Trial in PCNSL

Grzegorz S. Nowakowski, MD, consultant, Division of Hematology, Department of Internal Medicine, enterprise deputy director, Clinical Research, professor, oncology, medicine, Mayo Clinic Comprehensive Cancer Center, discusses the potential clinical implications of findings from the part B expansion cohort of the phase 1/2 TakeAim Lymphoma trial (NCT03328078), which is investigating the combination of the IRAK4 inhibitor emavusertib (CA-4948) and the BTK inhibitor ibrutinib (Imbruvica) in patients with relapsed or refractory primary central nervous system lymphoma (PCNSL).

The potential positive results from part B of the ongoing TakeAim Lymphoma trial on dual IRAK4 and BTK inhibition hold significant promise for the management of PCNSL and other B-cell malignancies, Nowakowski begins. With the development of BTK inhibitors in PCNSL, an agent such as emavusertib that synergizes with this class of drugs could rapidly enhance treatment strategies, he notes. If the activity signals that have been seen so far in the trial are sustained, emavusertib plus ibrutinib may move into the frontline setting for patients with PCNSL, he says.

Although the TakeAim Lymphoma trial targets a critical unmet need for patients with PCNSL, the dual inhibition of IRAK4 and BTK could play a crucial role in the management of other B-cell malignancies, including for patients who are refractory to BTK inhibitors, according to Nowakowski. He encourages oncologists to refer eligible patients to centers conducting the TakeAim Lymphoma study or enroll them to the trial if it is available at their institution. The potential for the broader application of emavusertib beyond PCNSL is significant, and this trial could influence the future use of BTK inhibitors across hematologic malignancies, he emphasizes. Expanding clinical investigations of emavusertib plus ibrutinib in patients with BTK inhibitor–refractory mantle cell lymphoma, chronic lymphocytic leukemia, and other B-cell lymphomas, will be essential to overcome resistance seen with available BTK inhibitors, he concludes.