TOPLINE

In patients with untreated primary central nervous system (CNS) lymphoma, consolidative high-dose chemotherapy with autologous stem cell transplantation (ASCT) significantly improved progression-free survival and overall survival compared with consolidative nonmyeloablative chemotherapy among those who achieved at least a partial response to induction. However, adverse events were higher in the high-dose chemotherapy–ASCT group.

METHODOLOGY

• Treatment with high-dose chemotherapy-ASCT after high-dose methotrexate-based induction (MATRix) has shown efficacy in patients with primary CNS lymphoma but can cause substantial toxicity. Additionally, its benefit over nonmyeloablative chemoimmunotherapy remains uncertain.
• To compare thiotepa-based high-dose chemotherapy-ASCT with nonmyeloablative chemoimmunotherapy consolidation, researchers conducted a phase 3 trial involving immunocompetent patients aged 18-70 years with untreated B-cell primary CNS lymphoma between July 2014 and August 2019.
• Overall, 346 patients received four cycles of MATRix (rituximab, methotrexate, cytarabine, and thiotepa) every 21 days, with stem cell harvest after cycle 2. Patients with at least a partial response (n = 230) were then randomly assigned to receive either two cycles of rituximab plus dexamethasone, etoposide, ifosfamide, and carboplatin (R-DeVIC) every 21 days or high-dose chemotherapy-ASCT conditioned with carmustine and thiotepa.
• The primary endpoint was progression-free survival, assessed in the full analysis set of 229 patients (R-DeVIC group: n = 115; median age, 60 years; high-dose chemotherapy-ASCT group: n = 114; median age, 58 years). The median follow-up duration was 45.3 months.
• Secondary endpoints were overall survival, complete response 60 days after randomization, duration of response (reported as cumulative incidence of relapse), quality of life using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire, and safety endpoints.

TAKEAWAY

• High-dose chemotherapy-ASCT significantly improved progression-free survival compared with R-DeVIC consolidation (hazard ratio [HR], 0.43; P = .0003); the median progression-free survival could not be determined in the high-dose chemotherapy-ASCT group and was 39 months in the R-DeVIC group, with the 36-month survival rate being 78% vs 51%.
• High-dose chemotherapy-ASCT significantly improved overall survival (HR, 0.46; P = .0075); the 3-year overall survival rate was 86% vs 71% in the high-dose chemotherapy-ASCT group vs the R-DeVIC group.
• The cumulative incidence rates of relapse at 36 months were significantly lower in the high-dose chemotherapy-ASCT group (19% vs 45%; subdistribution HR, 0.40). Complete response rates 60 days after randomization were similar between the groups: 69% vs 65% in the high-dose chemotherapy-ASCT group vs the R-DeVIC group (HR, 1.22).
• Patient-reported global health status improved slightly more over time with high-dose chemotherapy-ASCT; however, overall variability in the quality-of-life data was high. Adverse events were more frequent with high-dose chemotherapy-ASCT than with R-DeVIC (mean, 14.6 vs 9.3 events per patient); during induction, 58% of all patients experienced at least one serious adverse event, and 5% had a fatal serious adverse event, most commonly infection.

IN PRACTICE

The study, exploring the challenging setting of untreated primary CNS lymphoma, “provides important high-level evidence for the superiority of high-dose chemotherapy-ASCT” in the patient group responsive to MATRix induction, the authors of the study wrote.

SOURCE

The study, led by Gerald Illerhaus, MD, Stem-Cell Transplantation and Palliative Care, Tumorzentrum Eva Mayr-Stih, Klinikum Stuttgart, Stuttgart, Germany, was published online in The Lancet.

LIMITATIONS

Results applied only to the responders to induction therapy, limiting generalizability to the full cohort. The open-label design and investigator discretion in determining high-dose chemotherapy-ASCT eligibility may have introduced bias. In addition, the study was conducted in western Europe, which may limit generalizability to broader populations.

DISCLOSURES

The study received support from the German Federal Ministry of Research, Technology and Space; the Swiss Cancer Research Foundation; and RIEMSER Pharma. Illerhaus disclosed receiving research funding from RIEMSER Pharma and the German Federal Ministry of Research, Technology and Space; funding from Bristol Myers Squibb; honoraria for lecture fees from Johnson & Johnson, Roche, Kite, and Amgen; travel support from Johnson & Johnson, Roche, and Gilead Sciences; and participation on advisory boards for Bristol Myers Squibb, Roche, and Kite. Full disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.