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

Bromberg, J.E.C.; Issa, S.; Holt, B. van der; Meulen, M. van der; Dirven, L.; Minnema, M.C.; ... ; Doorduijn, J.K. (2024)

Article / Letter to editor

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.

• health-related quality of life
• neurocognitive function
• PCNSL
• rituximab
• treatment

• All authors: Bromberg, J.E.C.; Issa, S.; Holt, B. van der; Meulen, M. van der; Dirven, L.; Minnema, M.C.; Seute, T.; Durian, M.; Cull, G.; Poel, M.W.M. van der; Stevens, W.B.C.; Zijlstra, J.M.; Brandsma, D.; Nijland, M.; Mason, K.D.; Beeker, A.; Abrahamse-Testroote, M.C.J.; Bent, M.J. van den; Jong, D. de; Doorduijn, J.K.
• Date: 2024-04-05
• Journal: Neuro-Oncology
• Volume: 26
• Issue: 4
• Pages: 724 - 734
• DOI: doi:10.1093/neuonc/noad224
• Link: https://academic.oup.com/neuro-oncology/article/26/4/724/7456676