High-dose chemotherapy followed by autologous stem cell transplant (HDC-ASCT) improves outcomes, compared with chemoimmunotherapy, in previously untreated patients with primary central nervous system lymphoma (PCNSL), according to research presented at the 2022 ASH Annual Meeting.
In a phase 3 trial, HDC-ASCT improved progression-free survival (PFS) and overall survival (OS) when compared with rituximab plus dexamethasone, etoposide, ifosfamide, and carboplatin (R-DeVIC).
“This is the largest randomized, multicenter phase 3 trial investigating the impact of high-dose chemotherapy in untreated patients with primary CNS lymphoma not older than 70 years,” said study presenter Gerald Illerhaus, MD, of Klinikum Stuttgart in Germany.
The trial (ClinicalTrials.gov Identifier: NCT02531841) included 346 adults with newly diagnosed PCNSL. The patients received 4 cycles of induction with rituximab, methotrexate, cytarabine, and thiotepa (MATRix). Stem cells were harvested after cycle 2.
There were 229 patients who achieved at least a partial response to induction and were randomly assigned to receive R-DeVIC (n=115) or HDC-ASCT (n=114). The chemotherapy used in the ASCT arm was carmustine or busulfan plus thiotepa.
The median age was 59.9 years (range, 21-70) in the R-DeVIC arm and 58.5 years (range, 24-69) in the HDT-ASCT arm. Women were in the minority in both arms (46.1% and 43.0%, respectively), and nearly all patients had diffuse large B-cell lymphoma histology (98.2% and 97.4%, respectively).
The median follow-up was 45.3 months. In the R-DeVIC arm, the complete response (CR) rate was 40% before consolidation and 65.2% after consolidation. In the HDC-ASCT arm, the CR rate was 39.5% before consolidation and 67.5% after.
The 3-year PFS rate was significantly higher in the HDC-ASCT arm than in the R-DeVIC arm — 79% and 53%, respectively (hazard ratio [HR], 0.405; 95% CI 0.252-0.650; P =.0002).
HDC-ASCT was also associated with a 54% reduction in the risk of death. The 3-year OS rate was 86% with HDC-ASCT and 71% with R-DeVIC (HR, 0.456; 95% CI, 0.256-0.812; P =.0077).
“Progression-free survival and overall survival is significantly higher after high-dose chemotherapy compared to conventional immunochemotherapy with R-DeVIC, despite similar remission rates after consolidation,” Dr Illerhaus noted.
Grade 3-4 toxicities were more frequent in the HDC-ASCT arm than in the R-DeVIC arm, with the most common being neutropenia (75% vs 56%), thrombocytopenia (95% vs 83%), anemia (75% vs 69%), febrile neutropenia (63% vs 15%), infections (53% vs 14%), and oral mucositis (55% vs 0%).
Treatment-related deaths occurred in 3.4% of patients in the HDC-ASCT arm and 0% in the R-DeVIC arm. There was no difference in neurotoxicity between the arms.
Dr Illerhaus noted that the randomized OptiMATe trial (ClinicalTrials.gov Identifier: NCT04931368) is evaluating shorter induction with the MATRix regimen to reduce toxicity.
Disclosures: Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Illerhaus G, Ferreri AJM, Binder M, 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). Presented at ASH 2022. December 10-13, 2022. Abstract LBA-3.