RARE-29. HIGH-DOSE METHOTREXATE (HD MTX)-BASED TREATMENTS OF PRIMARY CNS LYMPHOMA: OPTIMAL DOSE REVISITED - A RETROSPECTIVE ANALYSIS OF OUTCOMES IN TERTIARY MEDICAL CENTER

Standard treatment regimens for PCNSL typically combine HD MTX in various doses with other cytotoxic drugs, with or without WBRT. To evaluate efficacy and tolerability of different MTX doses in PCNSL. We screened records of PCNSL patients treated in TASMC between 2003-2015. A comparison of safety and effectiveness of various MTX doses (ranging from 1.5 to 8 gm/m2) for response rate, OS and PFS was performed using Cox Proportional Hazard Model. Fifty-three cases treated with HD MTX at first line were available for analysis. The median age was 65 (31-84) and median KPS was 80 (40-100). Eight of 53 patients received concurrent cytotoxic therapies with MTX, 22/53 patients received rituximab with MTX, and 5/53 patients received WBRT. Twenty-eight patients (52.8%) were treated with MTX at the dose of 8 gm/m2 (Cohort A); all other patients received lower MTX doses according to their age, KPS, renal function, and protocols used at the time of treatment (Cohort B). The median number of MTX cycles was 4 (1-11). In cohort A, 56% had CR, 22% had PR and 22% had PD. The proportion of CR, PR and PD in cohort B was 17%, 29% and 54%, respectively. OS and PFS in cohort A were 30 and 13.5 months, as compared to 5 and 2 months in cohort B. HRs for OS in cohorts B and A, adjusted for known prognostic factors and confounders, were 5.56 (1.33-23.27), 3.91 (1.6-9.57), and 4.44 (1.87-10.58) after 12, 36 and 60 months, respectively. HRs for PFS in the same cohorts were 2.32 (0.92-5.88), 2.69 (1.15-6.31), and 3.03 (1.3-7.05). Treatment with HD MTX at the dose of 8 g/m2improved response rates, OS and PFS in patients with PCNSL after 12, 36 and 60 months, compared with treatment at lower MTX doses.