Dr Grommes on the Addition of Ibrutinib to R-MPV Induction in Newly Diagnosed PCNSL

"We were happy to see that 100% of patients had a response, and 97% actually achieved a CR or unconfirmed CR. Moreover, the regimen demonstrated strong durability, with the 2-year PFS rate exceeding 80%.”

Christian Grommes, MD, a neuro-oncologist and associate attending physician at Memorial Sloan Kettering Cancer Center, presented key findings from a phase 2 trial (NCT02315326) evaluating the addition of ibrutinib (Imbruvica) to the R-MVP regimen, comprising rituximab (Rituxan), methotrexate, vincristine, and procarbazine, in patients with newly diagnosed primary central nervous system lymphoma (PCNSL).

Results were presented at the 2025 Society for Neuro-Oncology Annual Meeting. Regarding safety, the treatment was found to be very well tolerated. There is typically concern that ibrutinib can cause atrial fibrillation or potentially fatal fungal infections like pneumocystis or Aspergillus, especially in the elderly patient population, but the study did not see these anticipated severe toxicities, Gromess noted. Only 2 patients developed atrial fibrillation, and there were no pneumocystis or aspergillus infections. Furthermore, no major hemorrhagic events, such as septal hematomas or hemorrhages, were observed, which was highly reassuring, he said.

Grommes noted that the dosing strategy—which avoided overlap between ibrutinib and methotrexate because patients received methotrexate in the hospital and started ibrutinib upon returning home—might have contributed to the favorable toxicity profile.

The regimen was also highly active, with all patients achieving a response. Complete responses (CRs) or unconfirmed CRs were achieved by 97% of patients. Moreover, the regimen demonstrated strong durability, with a 2-year progression-free survival (PFS) rate exceeding 80%. Of note, this high 2-year PFS rate was observed regardless of whether consolidation included a transplant, which was utilized in approximately 50% of the patient cohort. Grommes concluded by reasserting that this is a highly active regimen, although its role in the treatment paradigm still needs to be confirmed.