ALBERT

Beschreibung: INTRODUCTION Primary central nervous system lymphoma (PCNSL) in patients (pts) over 65 years old have poorer outcome compared to younger cohorts, as comorbidities, baseline performance status and susceptibility to iatrogenic toxicity impede adequate drug delivery (Kasenda et al, Ann Oncol, 2015). Balancing toxicity against treatment benefits remains a challenge in this age group. Recent trials have attempted to rationalize treatment aiming for reduced toxicity whilst maintaining CNS penetration. Efficacy of additional agents, such as oral alkylators (Fritsch et al, Leukemia 2017) has also been demonstrated. Most clinical trial cohorts underrepresent elderly pts and thus analysis of real-world outcomes and therapeutic practice is warranted. METHODS Consecutively diagnosed pts between 01/10/12 and 01/10/17, ≥65 years old in 14 tertiary UK centres were analysed retrospectively. Radiological exclusion of systemic disease and histological diagnosis were mandatory. Pts receiving any form of 1st line treatment including palliative (whole-brain radiotherapy [WBRT]/oral chemotherapy), best supportive care (BSC) or clinical trial were included. Diagnostic and referral pathways were audited. Baseline patient characteristics and treatment received was recorded in order to document current UK practice. Pts. were stratified into 4 treatment groups: single agent MTX; MTX with oral alkylator; high-intensity HI-MTX (MTX/AraC and MATRix) or palliative intent treatment (WBRT/oral alkylator/BSC). The study primary outcome was overall response rate (ORR) after induction. Secondary outcomes were PFS and OS. Additional variables were MTX clearance and the relative dose intensity (RDI) of MTX normalised with a reference of 14mg/m2. UV/MVA for ORR and Cox-regression for PFS and OS were used for identification of baseline predictors of response and survival. RESULTS 244 pts were included in the analysis with median age 71yrs (range 65-91) and 123 (50%) male. LDH (Elevated:104, 42%) and ECOG performance score (PS) (3-4: 87, 36%) were the only prognostic markers recorded. Median time from presenting scan to treatment was 33 days (IQR 22-48). Demographic characteristics are summarised in table 1. 80% of pts (n=192) received MTX based chemotherapy. 68% of pts 〉70yr and 50% 〉75yr received 〉1 cycle of MTX. MTX median cumulative dose delivered was 10.6 g/m2 (range 1.5-21), median number of cycles was 4 (range 1-6). Dose reductions of MTX occurred in 53/176 pts. (30%). Median time to MTX clearance was 3 days (range 1-18) and median RDI was 0.75 (range 0.11-1.5). TRM for MTX treated pts was 7.2%. 112 pts received rituximab (46%; 11% pre-2015 vs. 64% post-2015). 73 pts. (38%) received 3 cycles of HI-MTX and underwent consolidation experienced comparable outcomes to younger trial cohorts. MTX combination chemotherapy and MTX dose intensity were the strongest predictors of survival whilst rituximab was not a covariate for response or survival despite an increase in its use. Maximising cumulative MTX dose, particularly within more intensive protocols, may translate into improved ORR and survival in older pts with PCNSL. Table. Table. Disclosures Kassam: AbbVie: Equity Ownership. Culligan:Merck Sharp & Dohme (MSD): Honoraria; Celgene: Other: Support to attend conferences; Daiichi-Sankyo: Other: Support to attend conferences; JAZZ: Honoraria; Abbvie: Other: Support to attend conferences; Takeda: Honoraria, Other: Support to attend conferences; Pfizer: Honoraria. McKay:Epizyme: Consultancy, Honoraria. Eyre:Roche: Consultancy; Janssen: Consultancy, Other: travel support; Gilead: Consultancy, Other: travel support; Abbvie: Consultancy, Other: travel support; Celgene: Other: travel support. Osborne:Roche: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Servier: Consultancy; MSD: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Honoraria, Speakers Bureau; Novartis: Other: Travel to conference. Yallop:Servier: Other: Travel funding; Pfizer: Consultancy. Fox:Janssen: Consultancy, Other: Personal fees and non-financial support, Speakers Bureau; AbbVie: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Other: Travel support, Speakers Bureau; Sunesis: Consultancy; Roche: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Other: Travel support, Research Funding, Speakers Bureau. Cwynarski:Roche: Consultancy, Other: Conferences/Travel support, Speakers Bureau; Autolus: Consultancy; Kite: Consultancy; Gilead: Consultancy, Other: Conferences/Travel support, Speakers Bureau; Janssen: Other: Conferences/Travel support.