P15.06 Efficacy and prognostic factors of combined immunochemotherapy R-MPV-A with reduced or deferred radiotherapy for patients with primary CNS lymphoma

Backgrounds: R-MPV-A (rituximab plus high-dose (HD) methotrexate (MTX), procarbazine, vincristine followed by high-dose cytarabine) is an active regimen for primary central nervous system lymphoma (PCNSL). A high complete response (CR) rate by the R-MPV induction phase may allow reduction or abbreviation of neurotoxic whole brain radiotherapy (WBRT) with yet favorable outcome. Here we report our single institution experience of R-MPV-A therapy for patients with newly-diagnosed PCNSL to evaluate its efficacy, toxicity, preservation of neurocognitive function and white mater change, along with potential prognostic factors compared with those treated with HD-MTX alone in the previous era. Methods: Thirty-two cases with newly diagnosed PCNSL treated with R-MPV-A since 2012 with more than 6 months from the diagnosis were eligible. There were 19 males and 13 females, mean age was 69.3 yo (range 34-90, 53% were 70 or older), and median KPS was 70 (30-90). R-MPV was applied for 5 to 8 cycles. CR cases received either 24 Gy WBRT (< 70 yo) or no WBRT (>=70), followed by HD-cytarabine for 2 cycles. KPS, MMSE, and Fazekas score were recorded longitudinally. Known clinical factors and molecular factors including MGMT promoter methylation and MYD88 mutation, and expression of mismatch repair (MMR) proteins were also analyzed. Results: Most (88%) cases received 5 or more cycles of R-MPV and WBRT was dose-reduced or omitted in 85% of cases as planned. CR/CRu to R-MPV was achieved in 77%, while there were only 7 (22%) progressions and 4 (13%) deaths with median follow-up for 24.6 months (3.5-58). These outcomes were significantly better than those with previously used HD-MTX monotherapy plus WBRT where CR/CRu rate was 18% with mPFS 9.9 m and mOS 45.2 m. KPS improved in 73% and was maintained in 24, while MMSE and Fazekas score were improved or maintained in 20/23 (87%) and 21/26 (81%), respectively. KPS and MMSE scores dropped only at disease progression. No cases with WBRT omission experienced worsening of Fazekas score except for one with progression. Univariate analysis for PFS reveals single lesion (p=0.010), resection (vs. biopsy, p=0.015), age (=24, p=0.025), methylated MGMT (p=0.056), high expression of MSH6 (p=0.047), and Bcl-2 (p=0.036) as favorable factors. MYD88 L265P mutation status was not associated with PFS. Conclusions: R-MPV-A confers a high CR rate even in elderly patients with improvement and preservation of daily activity, neurocognitive and radiological status. MGMT and MSH6 status might predict outcome after R-MPV-A therapy. Further exploration may be needed for prognostic factors.