Researchers, led by Marion Alcantara, PhD, of Institut Curie in Saint-Cloud, France, examined ibrutinib, a Bruton’s tyrosine kinase (BTK) inhibitor, or lenalidomide, an immunomodulatory drug, in combination with standard high-dose methotrexate-based chemotherapy in patients with newly diagnosed primary central nervous system lymphoma (PCNSL). Their goal was to establish phase II dose recommendations, based on their phase Ib data on dose-limiting toxicities. They presented the results of their analysis at the 2023 American Society of Clinical Oncology Annual Meeting.
The study included 26 patients aged 18 to 60 years who were newly diagnosed with PCNSL. They were randomized to receive four 28-day cycles of either ibrutinib (n=13) or lenalidomide (n=13) in combination with R-MPV (rituximab, methotrexate, procarbazine, vincristine, and prednisone). Patients who responded then received consolidation treatment of intensive chemotherapy and autologous hematopoietic stem cell transplantation.
Four dose-limiting toxicities occurred. In the ibrutinib group, one patient had grade 5 aspergillosis and pneumocystosis. In the lenalidomide group, one patient had a grade 4 catheter-related infection, and two had grade 3 elevated alanine aminotransferase. Additional serious adverse events in the lenalidomide and ibrutinib groups, respectively, included Lyell’s syndrome (n=1 and 0), hepatic cytolysis (n=5 and 4), neutropenia (n=3 and 3), thrombocytopenia (n=0 and 2), anemia (n=0 and 2), lymphocytopenia (n=2 and 0), and sepsis (n=0 and 5).
After four cycles, three patients in the ibrutinib group had a complete response, and seven had a partial response. In the lenalidomide arm, six had a complete response, and four had a partial response. Based on the analysis, the authors recommended ibrutinib and lenalidomide doses of 560 mg and 15 mg, respectively, in combination with R-MPV.
“Targeted induction immunochemotherapy with ibrutinib or lenalidomide and R-MPV is feasible for newly diagnosed PCNSL and shows promising response rates,” the authors concluded. “Adverse events should be monitored carefully.” Enrollment for phase II is underway.
Reference
Alcantara M, Chevrier M, Jardin F, et al. Final analysis of the phase IB part of the LOC-R01 trial, a non-comparative randomized phase IB/II study of escalating doses of lenalidomide and ibrutinib in association with R-MPV for patients with a newly diagnosed primary central nervous system lymphoma (PCNSL). Abstract #7566. Presented at the 2023 American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, Illinois.
