CTNI-49. IBRUTINIB IN COMBINATION WITH RITUXIMAB, METHOTREXATE (MTX), VINCRISTINE, AND PROCARBAZINE (R-MPV/I) FOR NEWLY DIAGNOSED PRIMARY CNS LYMPHOMA (PCNSL)

Abstract BACKGROUND The R-MVP regimen results in a 66% complete response rate (CRR) in newly diagnosed PCNSL. The Bruton’s tyrosine kinase inhibitor ibrutinib showed single-agent activity in recurrent PCNSL. This phase 2 trial explored the combination of ibrutinib and R-MVP in newly diagnosed PCNSL. METHODS Eligible patients had newly diagnosed PCNSL, age≥18, ECOG≤2, and normal end-organ function. Treatment was administered over four 28-day cycles. Rituximab 500mg/m2 was given on Day 0 + 14, MTX 3.5g/m2 Day 1 + 15, vincristine 1.4mg/m2 Day 1 + 15 cycles 1-2, and procarbazine 100mg/m2/day Day 1-7 of each cycle. Ibrutinib 560mg/day was given Days 5-14 and 19-28 each cycle. Enrollment was allowed after 1-2 prior doses of methotrexate. The primary endpoint was CRR at end of induction The combination was considers promising if CRR (CR+CRu (if>95% reduction)) reached 80% (24 out of 30 patients) (90% power with a significance of 0.05). Secondary endpoints included safety and tolerability, median progression-free survival (PFS), and overall survival (OS). Consolidation was determined by the investigator. RESULTS Accrual is complete (n=30, median age 69 [range 41-79], median ECOG=1), 25 patients completed R-MPV/i, 1 withdrew consent after 2 R-MVP/i cycles and 4 are still receiving treatment. A CR was achieved in 25 and a PR in 1 for a CRR of 25/30 (83%) thus far. Treatment was well tolerated with 23 of 26 (88%) receiving 8 doses of MTX, 2 (8%) 7 doses and 1 (4%) 5 doses. No refractory disease was observed thus far. For the 25 completing R-MVP/i, 16 received Ara-C consolidation, 7 ASCT, and 1 rituximab maintenance. At a median follow up of 24 months (range 1-47), the median PFS and OS was not reached with a 2-year and 3-year PFS of 83.2%. CONCLUSIONS R-MPV/i induction regimen resulted in improved complete response rates and met the primary endpoint.