High-dose methotrexate combined with procarbazine and CCNU for primary CNS lymphoma in the elderly: results of a prospective pilot and phase II study

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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High-dose methotrexate for primary CNS lymphoma in the elderly

Neuro-Oncology ◽

10.1215/15228517-2-1-40 ◽

2000 ◽

Vol 2 (1) ◽

pp. 40-44 ◽

Cited By ~ 28

Author(s):

S. Ng

Keyword(s):

Primary Cns Lymphoma ◽

The Elderly ◽

Cns Lymphoma ◽

High Dose ◽

High Dose Methotrexate ◽

Dose Methotrexate

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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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Faculty Opinions recommendation of High-dose cytarabine plus high-dose methotrexate versus high-dose methotrexate alone in patients with primary CNS lymphoma: a randomised phase 2 trial.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1382969.855068 ◽

2010 ◽

Author(s):

Tali Siegal

Keyword(s):

Primary Cns Lymphoma ◽

Cns Lymphoma ◽

High Dose ◽

High Dose Methotrexate ◽

Phase 2 ◽

Phase 2 Trial ◽

Dose Methotrexate ◽

High Dose Cytarabine

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Treatment of HIV-associated primary CNS lymphoma with antiretroviral therapy, rituximab, and high-dose methotrexate

Blood ◽

10.1182/blood.2020006048 ◽

2020 ◽

Vol 136 (19) ◽

pp. 2229-2232

Author(s):

Kathryn Lurain ◽

Thomas S. Uldrick ◽

Ramya Ramaswami ◽

Mark N. Polizzotto ◽

Priscila H. Goncalves ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Primary Cns Lymphoma ◽

Cns Lymphoma ◽

High Dose ◽

High Dose Methotrexate ◽

Dose Methotrexate

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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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