High-dose chemotherapy with autologous stem cell transplant (HDC-ASCT) improves outcomes, when compared to conventional immunochemotherapy, in patients with newly diagnosed primary central nervous system (CNS) lymphoma, according to research presented at the International Conference on Malignant Lymphoma 2023.

“The progression-free survival and overall survival is significantly higher after high-dose chemotherapy and autologous stem cell transplant compared to conventional immunochemotherapy with R-DeVIC, despite similar response rates after consolidation,” said study presenter Gerald Illerhaus, MD, of Klinikum Stuttgart at Katharinenhospital in Germany.

These results come from the phase 3 MATRix trial (ClinicalTrials.gov Identifier: NCT02531841). The trial enrolled immunocompetent patients with newly diagnosed primary CNS lymphoma. Patients aged 66-70 years were only eligible if they had an ECOG performance status of 0-2. Younger patients could have any performance status.

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All patients received induction with 4 cycles of rituximab, methotrexate, cytarabine, and thiotepa (MATRix). Stem cell harvest occurred after cycle 2. Patients who had a partial response or greater were randomly assigned to receive 2 cycles of rituximab, dexamethasone, etoposide, ifosfamide, and carboplatin (R-DeVIC; n=115) or HDC-ASCT (chemotherapy consisted of carmustine or busulfan plus thiotepa; n=114).

Prior to consolidation, 40.0% of patients in the R-DeVIC arm and 39.5% of those in the HDC-ASCT arm had a complete response (CR) or unconfirmed CR (uCR). CR/uCR rates increased to 65.2% following R-DeVIC and 67.5% following HDC-ASCT.

“Despite the same remission rates, we see a big difference in progression-free survival of around 27%,” Dr Illerhaus noted.

The 3-year progression-free survival rate was 79% with HDC-ASCT and 52% with R-DeVIC (hazard ratio [HR], 0.396; 95% CI, 0.247-0.635; P =.0001).

Overall survival was significantly different between the arms as well, with a 54% reduction in the risk of death among patients treated with HDC-ASCT. The 3-year overall survival rate was 86% with HDC-ASCT and 71% with R-DeVIC (HR, 0.456; 95% CI, 0.255-0.810; P =.0075).

At a median follow-up of 45.3 months, the cumulative incidence of relapse was 41% with R-DeVIC and 16% with HDC-ASCT. The cumulative incidence of non-relapse mortality was 6.7% and 4.4%, respectively.

Neurocognitive evaluations showed improvements in both groups, with no difference in outcomes between the study arms, Dr Illerhaus said.

The incidence of grade 3-4 hematologic toxicities was higher in the HDC-ASCT arm than in the R-DeVIC arm. Patients in the HDC-ASCT arm also had higher rates of grade 3-4 infections (53% vs 14%) and grade 3-4 oral mucositis (55% vs 0%). Treatment-related deaths occurred in 3.4% of patients assigned to HDC-ASCT and 0% assigned to R-DeVIC.

“In order to reduce toxicity during induction therapy, a shorter induction therapy with R-MTX [rixuximab plus methotrexate] pretreatment followed by 2 cycles of MATRix is being tested in the randomized and ongoing OptiMATe trial [ClinicalTrials.gov Identifier: NCT04931368],” Dr Illerhaus said.

Disclosures: This research was supported Riemser and Roche. One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Illerhaus G, Ferreri A, Binder M, et al. Consolidative HCT-ASCT is superior to non-myeloablative chemo-immunotherapy in newly-diagnosed PCNSL – Updated results of the randomized phase III MATRIX/IELSG43 trial. ICML 2023. June 13-17, 2023. Abstract 15.

This article originally appeared on Cancer Therapy Advisor