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Clinical Trial
. 2024 Apr 5;26(4):724-734.
doi: 10.1093/neuonc/noad224.

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  1 , Samar Issa  2 , Bronno van der Holt  3   4 , Matthijs van der Meulen  5 , Linda Dirven  6   7 , Monique C Minnema  8 , Tatjana Seute  9 , Marc Durian  10 , Gavin Cull  11   12 , Marjolein W M van der Poel  13 , Wendy B C Stevens  14 , Josee M Zijlstra  15 , Dieta Brandsma  16 , Marcel Nijland  17 , Kylie D Mason  18 , Aart Beeker  19 , Martine C J Abrahamse-Testroote  3 , Martin J van den Bent  1 , Daphne de Jong  20 , Jeanette K Doorduijn  4
Affiliations
Clinical Trial

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 et al. Neuro Oncol. .

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.

Keywords: PCNSL; health-related quality of life; neurocognitive function; rituximab; treatment.

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Conflict of interest statement

J.E.C.B. reports financial support for trial management, travel expenses, and receiving Rituximab free of charge from Roche during the conduct of the study, consulting fees from Gilead and lecture fees from Novartis, and institutional funding of educational symposia from Roche and TEVA; M.J.B. reports consulting fees from Roche; J.K.D. reports financial support for trial management, travel expenses, and receiving Rituximab free of charge from Roche during the conduct of the study and lecture fees from Roche; M.N. reports research grants from Roche, Takeda, BMS, and Abbvie, and consulting fees from AbbVie; D.B. reports a research grant from the Dutch Cancer Society and from Gilead Sciences and lecture fees fee from Lilly Pharmaceuticals. S.I., M.vd.M., L.D., B.vd.H., M.C.M., T.S., M.D., G.C., M.vd.P., W.B.S., J.M.Z., D.B., K.D.M., A.B., M.T., and D.d.J. have declared no conflicts of interest.

Figures

Figure 1.
Figure 1.
Survival Curves. (A) Event-Free and (B) Overall Survival (C and D) Overall Survival by Age Group (≤60 years, >60 years) and (E and F) WHO Performance Status (0–1, 2–3)
Figure 2.
Figure 2.
Changes in Neurocognitive Function Over Time. Mean z-Scores (95% CI) Over Time for the Neurocognitive Domains (A) Information Processing Speed, (B) Memory, (C) Attention/Executive functioning and (D) Motor speed (Group-Level Analysis). Percentage of Patients with a Clinically Relevant Change (ie Change in z-Score > 1) in Neurocognitive Functioning Over Time as Compared to the Baseline Score, (E) Information Processing Speed, (F) Memory, (G) Attention/Executive Functioning, and (H) Motor Speed (Individual Level Analysis). For Each Time Point, the Number of Patients Included in the Analysis is Shown CT, chemotherapy; RT, radiotherapy; m, months; FU, follow-up.
Figure 3.
Figure 3.
Changes in HRQoL Scores Over Time. Mean (95% CI) HRQoL Scores Over Time for the Scales for (A) Global Health Status, (B) Social Functioning, (C) Role Functioning, (D) Fatigue, and (E) Motor Dysfunction (Group-Level Analysis). Percentage of Patients with a Clinically Relevant Change (ie Change of ≥10 Points) in HRQoL Scores Over Time as Compared to the Baseline Score, Separately for (F) Global Health Status, (G) Social Functioning, (H) Role Functioning, (I) Fatigue, and (J) Motor Dysfunction (Individual Level Analysis). For Each Time Point, the Number of Patients Included in the Analysis is Shown CT, chemotherapy; RT, radiotherapy; m, months; FU, follow-up.
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