Survival, neurocognitive function, and health-related quality of life outcomes after rituximab-methotrexate, BCNU, teniposide, and prednisolone for primary CNS lymphoma: Final results of the HOVON 105/ALLG NHL 24 study

Jacoline E. C. Bromberg*, Samar Issa, Bronno van der Holt, Matthijs van der Meulen, Linda Dirven, Monique C. Minnema, Tatjana Seute, Marc Durian, Gavin Cull, Marjolein W. M. van der Poel, Wendy B. C. Stevens, Josee M. Zijlstra, Dieta Brandsma, Marcel Nijland, Kylie D. Mason, Aart Beeker, Martine C. J. Abrahamse-Testroote, Martin J. van den Bent, Daphne de Jong, Jeanette K. Doorduijn

*Corresponding author for this work

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Abstract

Background. Studies on the efficacy of rituximab in primary CNS lymphoma (PCNSL) reported conflicting results. Our international randomized phase 3 study showed that the addition of rituximab to high-dose methotrexate, BCNU, teniposide, and prednisolone (MBVP) in PCNSL was not efficacious in the short term. Here we present long-term results after a median follow-up of 82.3 months. Methods. One hundred and ninety-nine eligible newly diagnosed, nonimmunocompromised patients with PCNSL aged 18–70 years with WHO performance status 0–3 was randomized between treatment with MBVP chemotherapy with or without rituximab, followed by high-dose cytarabine consolidation in responding patients, and reduced-dose WBRT in patients aged ≤ 60 years. Event-free survival was the primary endpoint. Overall survival rate, neurocognitive functioning (NCF), and health-related quality of life (HRQoL) were additionally assessed, with the IPCG test battery, EORTC QLQ-C30 and QLQ-BN20 questionnaires, respectively. Results. For event-free survival, the hazard ratio was 0.85, 95% CI 0.61–1.18, P = .33. Overall survival rate at 5 years for MBVP and R-MBVP was 49% (39–59) and 53% (43–63) respectively. In total, 64 patients died in the MBVP arm and 55 in the R-MBVP arm, of which 69% were due to PCNSL. At the group level, all domains of NCF and HRQoL improved to a clinically relevant extent after treatment initiation, and remained stable thereafter up to 60 months of follow-up, except for motor speed which deteriorated between 24 and 60 months. Although fatigue improved initially, high levels persisted in the long term. Conclusions. Long-term follow-up confirms the lack of added value of rituximab in addition to MBVP and HD-cytarabine for PCNSL.

Original languageEnglish
Pages (from-to)724-734
Number of pages11
JournalNeuro-Oncology
Volume26
Issue number4
Early online date1 Dec 2023
DOIs
Publication statusPublished - 1 Apr 2024

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