Author(s): Martinez-Calle N.; Kell M.; Cwynarski K.; Gibb A.; Cummin T.; Kassam S.; Yallop D.; Fabbri A.; Calimeri T.; Ferreri A.J.M.; Ambrosetti A.; Orsucci L.; Smith J.; Linton K.; Holl H.-G.; Kasenda B.; Davies A.; Schorb E.; Illerhaus G.; Fox C.
Source: British Journal of Haematology; Apr 2018; vol. 181 ; p. 80
Publication Date: Apr 2018
Publication Type(s): Conference Abstract
Available at British journal of haematology – from Wiley Online Library Full Collection
Abstract:Introduction: Current treatment of newly diagnosed primary CNS lymphoma (PCNSL) in the UK is based on the randomized IELSG32 trial, which demonstrated that MATRix regimen (methotrexate [MTX], cytarabine [AraC], thiotepa, rituximab) followed by consolidation significantly improved survival. However, IELSG32 was restricted to patients younger than 70 yrs with ECOG <=2 (and <65 yrs PS <= 3) and thus, the real-world PCNSL population might differ from that of the trial. Therefore, a real world evaluation of this treatment strategy is desired. We conducted a multicentre study of clinical outcomes in PCNSL patients treated with MATRix in routine practice. Methods: Retrospective review of newly diagnosed PCNSL patients treated with MATRix regimen (6 UK and 7 European tertiary cen-tres), off trial, between 2010-2017. Patients who received at least 1 MATRix cycle were included. Study endpoints were theoretical eligibility for IELSG32 trial, treatment delivery, rate of (serious) adverse events and infections, remission status after MATRix therapy, progression free survival (PFS) and overall survival (OS). Results: Of 114 patients, 44% were female, with a median age of 60 years (28-76). Median KPS was 60% (30-100), 25/114 had ECOG >= 3. Thirty-six patients (32%) would not have met IELSG32 trial criteria: performance status n = 10; age n = 15; inadequate organ function n = 10; previous malignancy n = 3; HIV infection n = 2. Treatment delivery was 82% (377/456 planned cycles), of which 154 (41%) were dose reduced. Reasons for dose reduction were mainly PS (29%) and haematological toxicity (38%). 74 patients (65%) completed all 4 courses, but 100% dose intensity across all 4 cycles was only delivered in 32/114 patients. 67/114 patients (59%) underwent consolidation treatment (HDT-ASCT: 53pts; WBRT: 12pts; TMZ: 2pts). There were 8 deaths during treatment, 4 were attributable to infection. Treatment was interrupted in another 32 patients due to: Grade 3-4 infections n = 12; non-haematological toxicities n = 7; disease progression n = 8; poor PS n = 3. In total, 63% of patients experienced an infectious episode during treatment of which 97% were deemed severe, however infections were only reported in 101/377 cycles (27%). After MATRix induction, 98 patients were evaluable. Overall response rate was 89.7% (51% PR, 38% CR). Early MRI assessment (before cycle 3) was available in 90% of patients (103/114), showing chemosensitive disease in 91% of cases (83pts PR/11pts CR). ORR after completing all first line treatment (ITT analysis) was 75% (86/114) with a CR rate of 50% (57/114). Twenty-five patients were consolidated in PR, of whom 14 (56%) achieved CR, 7 progressed and 5 remained disease-free. With a median follow-up of 16 months (2-69 months), median OS was not reached and median PFS was 42 months (CI 95% 11-73). 2-year OS and PFS were 67% and 69% respectively. Conclusions: Amongst a real-world population of MATRix-treated PCNSL patients, one third would have been ineligible for the IELSG32 trial. Notwithstanding an older and less-fit cohort, treatment delivery was high; incidence of infections per cycle was low and TRM almost identical to the IELSG32 cohort. CR rates after MATrix appeared lower than those in IELSG32, however we observed a higher ASCT rate and comparable survival outcomes to the trial. These data validate feasibility and efficacy of a MATRix-like approach for real world newly diagnosed PCNSL patients.