ML-08 THE ROLE OF MAINTENANCE HIGH-DOSE METHOTREXATE CHEMOTHERAPY IN ELDERLY PRIMARY CNS LYMPHOMA PATIENTS

Abstract BACKGROUND The addition of high-dose methotrexate (HD-MTX)-based chemotherapy to whole brain irradiation (WBRT) has improved the prognosis of primary central nervous system lymphoma (PCNSL). However, the high neurotoxicity rates observed, especially in the elderly, raised interest in chemotherapy-only treatments. Withholding radiotherapy substantially decreases the risk of neurotoxicity, however, disease control may be compromised. In the elderly who cannot tolerate WBRT as a consolidation, maintenance treatment may serve as a feasible approach after an initial response. We treated ePCNSL with induction immunochemotherapy, maintenance chemotherapy with HD-MTX and deferred WBRT. Here, we retrospectively investigated the prognosis for ePCNSL that became CR after the induction chemotherapy. MATERIAL AND METHODS Newly diagnosed ePCNSL (median age: 74 years) received biweekly rituximab/HD-MTX for 6 cycles (induction) followed by monthly rituximab/HD-MTX for 2 cycles (consolidation) and then were treated differently according to the radiological response. With CR patients, HD-MTX was continued with every 3 months (maintenance) for 2 years. Patients who did not obtain consent for maintenance therapy were followed up. For PD patients, immunochemotherapy was interrupted and WBRT initiated immediately. Patients with PR and SD were treated with alternative chemotherapy with temozolomide and/or stereotactic radiotherapy or WBRT. RESULTS The median PFS was 24.6 months and median OS was 27 months for the entire cohort. Of the 42 ePCNSL, 26 had CR after induction and consolidation, of which 18 cases were carried out maintenance (M+) and 8 cases were followed up (M-). Median PFS was 73 months in the M+ group and 24.5 months in the M- group. Median OS is 102.2months versus 27.6 months, respectively. Both mPFS (P= 0.0125) and mOS (P =0.0015) were significantly prolonged by maintenance therapy. CONCLUSION It was suggested that maintenance treatment with HD-MTX may improve the prognosis for ePCNSL that reached complete response after induction therapy.

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P14.113 The role of maintenance high-dose methotrexate chemotherapy in elderly primary CNS lymphoma patients with complete response to induction immunochemotherapy

Neuro-Oncology ◽

10.1093/neuonc/noz126.348 ◽

2019 ◽

Vol 21 (Supplement_3) ◽

pp. iii95-iii95

Author(s):

K Mishima ◽

M Shirahata ◽

J Adachi ◽

T Suzuki ◽

T Fujimaki ◽

...

Keyword(s):

Maintenance Therapy ◽

Maintenance Treatment ◽

Primary Cns Lymphoma ◽

Central Nervous System Lymphoma ◽

Complete Response ◽

The Elderly ◽

Cns Lymphoma ◽

High Dose ◽

High Dose Methotrexate ◽

Dose Methotrexate

Abstract BACKGROUND The addition of high-dose methotrexate (HD-MTX)-based chemotherapy to whole brain irradiation (WBRT) has improved the prognosis of primary central nervous system lymphoma (PCNSL). However, the high neurotoxicity rates observed, especially in the elderly, raised interest in chemotherapy-only treatments. Withholding radiotherapy substantially decreases the risk of neurotoxicity, however, disease control may be compromised. Therefore, developing a novel treatment for the elderly PCNSL patients (ePCNSL) is crucial. In the elderly who cannot tolerate WBRT as a consolidation, maintenance treatment may serve as a feasible approach after an initial response. We treated ePCNSL with induction immunochemotherapy with rituximab (RIT) and HD-MTX, maintenance chemotherapy with HD-MTX and deferred WBRT. Here, we retrospectively investigated the prognosis for ePCNSL that became CR after the induction chemotherapy. MATERIAL AND METHODS Newly diagnosed ePCNSL (median age: 74 years) received biweekly RIT/ HD-MTX (375 mg/m2/dose; 3.5g/m2/dose) for 6 cycles (induction) followed by monthly RIT/MTX for 2 cycles (consolidation) and then were treated differently according to the radiological response. With CR patients, HD-MTX was continued with every 3 months (maintenance) for 2 years. Patients who did not obtain consent for maintenance therapy were followed up. RESULTS Of the 42 ePCNSL (median age 74 years), 26 had CR after induction and consolidation, of which 18 cases were carried out maintenance (M +) and 8 cases were followed up (M-). The median age was 74 and 76, respectively. Median progression-free survival (mPFS) was 73 months in the M+ group and 24.6 months in the M- group. Median overall survival (mOS) is 92.5 months versus 27.6 months, respectively. Both mPFS (P= 0.025) and mOS (P =0.0003) were significantly prolonged by maintenance therapy. In addition, ePCNSL with tumors involvement of deep brain structure had a poor prognosis. CONCLUSION It was suggested that maintenance treatment with HD-MTX may improve the prognosis for ePCNSL that reached complete response after induction therapy.

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High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials

Scientific Reports ◽

10.1038/s41598-020-80724-0 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Junyao Yu ◽

Huaping Du ◽

Xueshi Ye ◽

Lifei Zhang ◽

Haowen Xiao

Keyword(s):

Meta Analysis ◽

Primary Cns Lymphoma ◽

Central Nervous System Lymphoma ◽

Progression Free Survival ◽

Complete Response ◽

Cns Lymphoma ◽

High Dose ◽

High Dose Methotrexate ◽

Newly Diagnosed ◽

Dose Methotrexate

AbstractWith the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.

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Treatment of primary CNS lymphoma with induction high-dose methotrexate, temozolomide, rituximab followed by consolidation cytarabine/etoposide: A pilot study with biomarker analysis

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7595 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 7595-7595 ◽

Cited By ~ 1

Author(s):

S. Issa ◽

J. Hwang ◽

J. Karch ◽

J. Fridlyand ◽

M. Prados ◽

...

Keyword(s):

Induction Therapy ◽

Primary Cns Lymphoma ◽

Cns Lymphoma ◽

High Dose ◽

High Dose Methotrexate ◽

Whole Brain Irradiation ◽

Whole Brain ◽

Brain Irradiation ◽

Dose Methotrexate ◽

Biomarker Analysis

7595 Background: There is currently no consensus on the optimal treatment for patients diagnosed with primary CNS lymphoma (PCNSL). Between 2001–2004, UCSF PCNSL patients were treated with combination high-dose methotrexate, temozolomide, rituximab (MTR) as induction therapy. Patients in CR with this regimen were treated with high-dose cytarabine plus etoposide as consolidation. The purposes of this study were: (1) Pilot analysis to determine the safety and efficacy of intensive methotrexate-based induction therapy followed by high-dose consolidation with elimination of whole brain irradiation; (2) Analysis of molecular markers in PCNSL which predict sensitivity to chemotherapy and outcome. Methods: 21 untreated, CD20 +, immunocompetent PCNSL patients were treated with combination methotrexate (8 gm/m²), temozolomide (150 mg/m²/day)and rituximab (375 mg/m²). Patients in CR received consolidation cytarabine (2 g/ m² x 8 doses) plus etoposide (40 mg/kg over 96 hours). IHC analysis of potential biomarkers predictive of outcome was performed on paraffin sections from these patients. Candidate markers for validation were selected by gene expression analysis of an independent, multicenter dataset of 20 cases. Results: Mean age was 58.6 y (range 40–81). Median KPS was 60. MTR and cytarabine/etoposide consolidation was well-tolerated with no treatment-related mortality or evidence for neurotoxicity. One case of post-remission cytopenia occurred after consolidation and resolved spontaneously. Eleven patients (52.4%) attained CR with induction; eight received consolidation; three patients in CR deferred consolidation. Median PFS was 11.5 months. Median OS for all 21 patients has not yet been reached with median follow-up of 27.5 months. Expression of the apoptotic regulator DAP-1 by lymphoma cells as determined by IHC was associated with improved PFS (p<0.028) and OS (p<0.021). Conclusions: Combination MTR followed by intensive consolidation appears to be well tolerated in PCNSL. PFS appears at least similar to regimens that contain whole brain irradiation. A larger phase II study has been initiated to evaluate this regimen in a multicenter setting. [Table: see text]

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Treatment outcomes of patients with primary central nervous system lymphoma: Single center experience from south India.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e13010 ◽

2013 ◽

Vol 31 (15_suppl) ◽

pp. e13010-e13010

Author(s):

Krishna Mohan V T Mallavarapu ◽

Santa Ayyagari ◽

Senthil Jagannathan Rajappa ◽

Krishnam Raju Alluri ◽

Sudha Murthy S

Keyword(s):

Overall Survival ◽

Treatment Outcomes ◽

Treatment Protocol ◽

Primary Cns Lymphoma ◽

Central Nervous System Lymphoma ◽

Cns Lymphoma ◽

High Dose ◽

High Dose Methotrexate ◽

Single Center Experience ◽

Dose Methotrexate

e13010 Background: Primary CNS Lymphoma (PCNSL) is a rare neoplasm of the brain accounting for 1-2% of all brain tumours. Incidence and histopathologic features of PCNSL in India has been reported; however, reports on therapy outcomes of the disease are lacking. We report treatment outcomes of patients with PCNSL at our institute. Methods: Case records of all patients treated for PCNSL between 2008 and 2012 were retrospectively analysed. Epidemiologic details, treatments given, progression free and overall survival were calculated. Patients who completed at least high dose methotrexate (1.5 gram/ m2) for 5 courses with or without RT were included for analysis. Overall survival (OS) was defined as time from diagnosis till death/lost to follow up. Results: A total of seventeen patients were analysed. The median age at diagnosis was 58 years and M: F ratio was 1.14:1. Thirteen out of seventeen patients were eligible for analysis; six could complete the total treatment protocol which included methotrexate, vincristine, procarbazine, Dexamethasone, Radiation therapy followed by high dose cytarabine. Median overall survival was 20 months (range 2-54 months). Among those who completed the protocol, median survival at 21 months was not reached with 66% survival. Conclusions: Treatment of PCNSL with at least high dose methotrexate with or without whole brain radiation offers moderate results. Completion of treatment protocol is associated with better overall survival.

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