Phase III MATRix/IELSG43 trial: HCT–ASCT vs non-myeloablative R-DeVIC consolidation in PCNSL

Results from the randomized, international, phase III MATRix/IELSG43 trial (NCT02531841) evaluating high-dose chemotherapy (HCT) with carmustine or busulfan + thiotepa followed by autologous stem cell transplantation (HCT–ASCT) vs non-myeloablative rituximab + dexamethasone + etoposide + ifosfamide + carboplatin (R-DeVIC) as consolidation therapy in 229 immunocompetent patients with newly diagnosed B-cell primary central nervous system lymphoma (PCNSL). Patients with at least a partial response to four cycles of induction with rituximab + high-dose cytarabine + thiotepa + high-dose methotrexate (MATRix) were randomly assigned (1:1) to R-DeVIC or HCT–ASCT. Results were published in The Lancet by Illerhaus et al. The primary end point was progression-free survival (PFS).

Key data: At a median follow-up of 45.3 months, 3-year PFS was significantly higher in the HCT–ASCT group vs the R-DeVIC group (78% vs 51%; hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.27–0.68; p = 0.0003). Median overall survival (OS) was not reached in either group but was prolonged with HCT-ASCT vs R-DeVIC (HR, 0.46; 95% CI, 0.26–0.81; p = 0.0075). The 3-year OS was 86% with HCT–ASCT vs 71% with R-DeVIC. The mean number of adverse events per patient was higher in the HCT–ASCT group vs the R-DeVIC group (14.6 vs 9.3). Fatal serious adverse events following consolidation treatment occurred in two patients in the R-DeVIC group and in five patients in the HCT–ASCT group.

Key learning: In the largest randomized trial in untreated PCNSL to date, thiotepa-based HCT–ASCT significantly improved PFS and OS compared with non-myeloablative R-DeVIC consolidation following MATRix induction, supporting HCT–ASCT as the potential preferred consolidation strategy for treatment-responsive patients. Limitations include the open-label design, potential selection bias in HCT–ASCT eligibility assessment, and a study population restricted to Western Europe.