Rituximab is associated with improved survival for aggressive B cell CNS lymphoma

Gregory, Gareth P.; Arumugaswamy, Ashwini; Leung, Teresa; Chan, Kah Lok; Abikhair, Melody; Tam, Constantine S.; Bajel, Ashish; Cher, Lawrence; Grigg, Andrew; Ritchie, David; Opat, Stephen

doi:10.1093/neuonc/not032

Cited by 62 publications

(31 citation statements)

References 27 publications

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“…In contrast to our results, a few retrospective studies have noted improved outcome in patients with PCNSL treated with combined rituximab and MTX‐based therapy . However, due to differing treatment schedules, doses delivered and patient heterogeneity, drawing comparisons is challenging.…”

Section: Discussioncontrasting

confidence: 99%

“…While their findings appear superior to our results (CR 37% for the rituximab arm, six month PFS 44%), this may again largely reflect differing treatment protocols and baseline patient demographics. A retrospective multicentre study from Australia compared patients receiving chemo‐immunotherapy ( n = 18) versus chemotherapy alone ( n = 99), and found that the inclusion of rituximab was associated with a better median OS (not reached versus 40 months, P = 0.023) . However, chemotherapy delivered included varying doses of HDMTX used (2 to 8 g/m 2 ), the incorporation of cytarabine in some patients and the higher dose of rituximab administered (500 mg/m 2 ).…”

Section: Discussionmentioning

confidence: 99%

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Rituximab with high‐dose methotrexate in primary central nervous system lymphoma

et al. 2015

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The addition of rituximab (R) to chemotherapy improves outcomes in patients with systemic B-cell nonHodgkin lymphomas, but the impact in patients with primary central nervous system lymphoma (PCNSL) receiving high-dose methotrexate (HDMTX) is unknown. Patients diagnosed with PCNSL at the British Columbia Cancer Agency (BCCA) between 2000 and 2013 were treated with 1 cycle of HDMTX 8 g/m 2 every 2 weeks, to best response or 10 cycles. After 2006, rituximab 375 mg/m 2 was given every 2 weeks with HDMTX for a total of 4 doses. 49 (66%) patients received HDMTX alone and 25 (34%) HDMTX1R, with a median of 5 (range 1-10) HDMTX cycles, and no difference between groups. The median follow-up was 5 years: 8.8 years (range 3.15-13.5 years) HDMTX and 1.9 years (range 0.5-7 years) HDMTX1R. The 5-year PFS was 17%, with no difference between groups (HR: 0.75, 95% CI: 0.41-1.35; P 5 0.33). The 5-year OS was 38%, with no difference between the groups OS (HR: 0.73, 95% CI: 0.35-1.52; P 5 0.39). In this retrospective study comparing two subgroups of patients treated in different eras, the addition of R to HDMTX did not appear to improve outcomes in PCNSL, possibly consistent with its known poor CNS penetration. It is possible that with a larger sample size, longer follow-up, or different rituximab dosing/schedule, the addition of rituximab may lead to a statistically significant improvement in outcomes. Prospective randomized trials currently in progress will more definitively estimate the impact of the addition of rituximab to HDMTX-based chemotherapy for PCNSL.

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rituximab with high‐dose methotrexate in primary central nervous system lymphoma

et al. 2015

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“…Our study represents the largest retrospective series, outside of clinical trials, that evaluates the utility of rituximab as an adjunct to cytotoxic therapy in PCNSL, showing similar results to most retrospective series of improved outcomes in PCNSL (Holdhoff et al , ; Birnbaum et al , ; Gregory et al , ). Doses of MTX and/or rituximab, use of additional cytotoxics and number of cycles were variable across these studies.…”

Section: Discussionsupporting

confidence: 69%

Impact of treatment variability on survival in immuno‐competent and immuno‐compromised patients with primary central nervous lymphoma

et al. 2017

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Patients with primary central nervous system lymphoma (PCNSL) treated in the 'real-world' setting do not represent those treated on clinical trials and might not be treated similarly. We studied characteristics and variability in care for 113 newly diagnosed PCNSL patients treated at 5 institutions in the Chicago area between 2000 and 2012. In 111 patients, single modality therapy with a high dose methotrexate (HD-MTX) regimen +/- rituximab, was most commonly employed (n = 65), and 34 underwent radiotherapy (+/- systemic therapy). Fifty-eight of 108 patients received rituximab. Twenty-nine of 110 patients (26%) received intrathecal chemotherapy (ITC). Overall response rate was 80% (47% complete responses). With a median follow-up of 18·7 months, median overall survival (OS) was 65·2 months. In univariate analysis, HD-MTX (median OS 72·7 vs. 2·7 months, P < 0·001) and rituximab (median not reached versus 28·4 months, P = 0·005) impacted OS favourably. This significance was sustained regardless of immune status and in multivariate analysis. Whole brain radiotherapy (WBRT) resulted in a trend for improved OS as compared with systemic therapy alone (P = 0·09), while ITC did not impact survival. Clinical practice has evolved to exclude WBRT and ITC while incorporating rituximab with clinical outcomes comparable in immuno-competent/compromised patients and similar to those achieved in recent clinical trials.

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“…6 nature of the published studies. 13,14 Ongoing large prospective trials, such as the NCT01011920 and NTR2427, should help to establish the role of additional rituximab for PCNSL treatment. 15 Unfortunately, although patients initially respond to treatment, relapse is not uncommon.…”

Section: Discussionmentioning

confidence: 99%

Primary Central Nervous System Anaplastic Large Cell Lymphoma is an Unusual Brain Tumour

Papadatos-Pastos¹,

Hall²,

Pettengell³

et al. 2014

European Oncology &Amp; Haematology

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We present a case of a 64-year-old man who was diagnosed with a primary anaplastic large cell lymphoma of the central nervous system (PCNSAL). He had received radical chemotherapy and radiotherapy for a non-small cell lung cancer (NSCLC) in the past. There is no known association between NSCLC and PCNSAL. We describe the diagnostic and therapeutic challenges associated with these rare intracranial lymphomas and highlight the potential role of newer biological agents in patients with anaplastic lymphoma kinase (ALK-1) positive PCNSAL.

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Rituximab is associated with improved survival for aggressive B cell CNS lymphoma

Abstract: In this retrospective analysis, the addition of rituximab to high-dose methotrexate-based chemotherapy in patients with aggressive B cell CNS lymphoma was associated with improved overall survival. Further studies are underway to prospectively validate these findings.

Cited by 62 publications

References 27 publications

Rituximab with high‐dose methotrexate in primary central nervous system lymphoma

Rituximab with high‐dose methotrexate in primary central nervous system lymphoma

Impact of treatment variability on survival in immuno‐competent and immuno‐compromised patients with primary central nervous lymphoma

Primary Central Nervous System Anaplastic Large Cell Lymphoma is an Unusual Brain Tumour

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