High-dose chemotherapy plus ASCT superior to standard immuno-chemotherapy in primary CNS lymphoma 

Consolidation high-dose chemotherapy followed by autologous stem cell transplantation (HCT/ASCT) significantly improved overall survival (OS) and progression-free survival (PFS) compared with consolidation non-myeloablative immuno-chemotherapy in patients with primary CNS lymphoma.

The phase 3 MATRix/IELSG43 trial (NCT02531841) included immunocompetent patients with newly diagnosed primary CNS lymphoma to receive 4 cycles of MATRIx immuno-chemotherapy. Hereafter, responders (n=230) were randomised 1:1 to receive 2 cycles of consolidation R-DeVIC immuno-chemotherapy or HCT/ASCT. The chemotherapy regimen consisted of carmustine and thiotepa or busulfan and thiotepa. Prof. Gerald Illerhaus (Klinikum Stuttgart, Germany) presented the PFS results, the primary endpoint of this trial [1].

After a median follow-up of 45.3 months, the PFS was significantly longer in the HCT/ASCT arm than in the R-DeVIC arm (HR 0.41; 95% CI 0.25–0.65; P=0.0002), with corresponding 3-year PFS rates of 79% and 53%. Likewise, OS was improved in the HCT/ASCT arm compared with the R-DeVIC arm (HR 0.46; 95% CI 0.26–0.81; P=0.0077). The 3-year OS rates were 86% and 71%, respectively.

Haematological adverse events (AEs) of grade 3 and 4 appeared to occur more often in the HCT/ASCT arm than in the R-DeVIC arm: neutropenia (75% vs 56%), thrombocytopenia (95% vs 83%), and anaemia (75% vs 69%). Also, grade 3 and 4 infections (53% vs 14%) and oral mucositis (55% vs 0%) were more prevalent in the HCT/ASCT arm.

The current phase 3 trial showed that HCT/ASCT results in improved PFS and OS rates compared with R-DeVIC therapy in patients with newly diagnosed primary CNS lymphoma. In order to reduce adverse events during the induction phase, a shorter induction therapy with R-MTX pre-treatment and 2 cycles of MATRix is currently being investigated in the OptiMATe trial (NCT04931368).

1. Illerhaus G, et al. Effects on Survival of Non-Myeloablative Chemoimmunotherapy Compared to High-Dose Chemotherapy Followed By Autologous Stem Cell Transplantation (HDC-ASCT) As Consolidation Therapy in Patients with Primary CNS Lymphoma - Results of an International Randomized Phase III Trial (MATRix/IELSG43). Late-Breaking Abstract 3, ASH 64^th Annual Meeting, 10–13 December 2022, New Orleans, LA, USA.

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Posted on 20 February 202318 March 2024