Ibrutinib in combination with rituximab, methotrexate, vincristine, and procarbazine for newly diagnosed primary CNS lymphoma

BACKGROUND: High-dose methotrexate-based chemotherapy is the mainstay of treatment of primary central nervous system lymphoma (PCNSL). Only ∼60% of patients achieve a complete response to first-line therapy with frequent relapses. The Bruton's tyrosine kinase inhibitor ibrutinib has shown promising antitumor activity in recurrent/refractory PCNSL. METHODS: The goal of the current single-center phase 2 trial was to explore whether the addition of ibrutinib to the combination of rituximab, methotrexate, procarbazine, and vincristine (R-MVP/i) increases complete response rate (CCR). RESULTS: Thirty newly diagnosed PCNSLs were enrolled; median age 69 (range 41-79), median Eastern Cooperative Oncology Group (ECOG) = 1. Twenty-nine patients completed R-MVP/i, 1 withdrew consent after 2 cycles. A complete response (CR)/complete response unconfirmed (CRu) was achieved in 29 patients and a partial response in 1 for a CRR of 29/30 (97%, 95% CI: 83.3%, 99.8%). Treatment was well tolerated with no grade 5 toxicity observed. Eight patients experienced 13 grade 4 toxicities (lymphopenia [n = 3], neutropenia [n = 4], thrombocytopenia [n = 3], and white cell count decrease [n = 3]). The most common toxicities were thrombocytopenia, anemia, lymphopenia, and liver enzyme elevations. No Aspergillus or Pneumocystis infections occurred. No refractory disease was observed. For the 29 patients completing the trial, 19 received consolidation with cytarabine (Ara-C), 8 autologous stem cell transplant, 1 rituximab maintenance, and 1 was observed without maintenance or consolidation. At a median follow-up of 25.1 months (range 3.3-49.2), the median progression-free (PFS) and overall survival were not reached with a 2-year PFS of 84.2% (95% CI: 62.7%-93.9%). CONCLUSIONS: R-MVP/i was well tolerated and associated with excellent disease control and survival.