Chemotherapy Alone as Initial Treatment for Primary CNS Lymphoma in Patients Older Than 60 Years: A Multicenter Phase II Study (26952) of the European Organization for Research and Treatment of Cancer Brain Tumor Group

2003 ◽  
Vol 21 (14) ◽  
pp. 2726-2731 ◽  
Author(s):  
K. Hoang-Xuan ◽  
L. Taillandier ◽  
O. Chinot ◽  
P. Soubeyran ◽  
U. Bogdhan ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Objective Response ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Karnofsky Performance Score ◽  
European Organization ◽  
Multicenter Phase

Purpose: To assess the efficacy and toxicity of chemotherapy alone in patients older than 60 years with primary CNS lymphoma. Patients and Methods: Fifty patients with a median age of 72 years and a median Karnofsky performance score (KPS) of 50 were eligible for this multicenter phase II study. The protocol consisted of high-dose methotrexate (MTX), lomustine, procarbazine, methylprednisolone, and intrathecal chemotherapy with MTX and cytarabine. The patients received one induction cycle; if objective response was achieved, five additional maintenance cycles were administered every 6 weeks. The median follow-up of patients was 3 years. Results: Twenty four patients (48%) achieved an objective response (compete response [CR], 42%; partial response, 6%), with a median duration of CR of 27 months (range, 3 to 47+ months). Overall median survival time was 14.3 months, and 1-year progression-free survival was 40% (95% confidence interval [CI], 26% to 53%). Myelosuppression was the most frequent side effect, with grade 3 to 4 neutropenia in 19% of patients. One patient died during chemotherapy, as a result of pulmonary embolism. Most patients improved or preserved their cognitive functions (47% and 45% of the patients, respectively) and KPS (36% and 52% of the patients, respectively) until relapse, whereas cognitive and KPS decline attributed to delayed treatment neurotoxicity occurred in 8% and 12% patients, respectively. Conclusion: In the elderly, this chemotherapy regimen compares favorably with radiotherapy (RT) alone and reduces considerably the risk of delayed neurotoxicity associated with combined chemoradiotherapy. Chemotherapy alone is an appropriate strategy in older patients to delay or avoid RT.

High-Dose Methotrexate-Based Chemotherapy Followed by Consolidating Radiotherapy in Non–AIDS-Related Primary Central Nervous System Lymphoma: European Organization for Research and Treatment of Cancer Lymphoma Group Phase II Trial 20962

2003 ◽  
Vol 21 (24) ◽  
pp. 4483-4488 ◽  
Author(s):  
Philip M.P. Poortmans ◽  
Hanneke C. Kluin-Nelemans ◽  
Hanny Haaxma-Reiche ◽  
Mars Van’t Veer ◽  
Mads Hansen ◽  
...  
Keyword(s):  
Response Rate ◽  
Objective Response ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
High Response Rate ◽  
Cns Lymphoma ◽  
High Dose ◽  
European Organization ◽  
Specialized Care ◽  
Intent To Treat

Purpose: To confirm the feasibility and estimate the efficacy of methotrexate (MTX), teniposide, carmustine, and methylprednisolone (MBVP) chemotherapy combined with radiotherapy (RT) for patients with non–AIDS-related primary CNS lymphoma (PCNSL) treated in a multicenter setting. Patients and Methods: Treatment consisted of two cycles of MBVP (MTX 3 g/m2 days 1 and 15, teniposide 100 mg/m2 days 2 and 3, carmustine 100 mg/m2 day 4, methylprednisolone 60 mg/m2 days 1 to 5, and two intrathecal injections of MTX 15 mg, cytarabine 40 mg, and hydrocortisone 25 mg) followed by 40 Gy of RT. Primary end points were response and safety of this regimen. Results: Twelve centers included 52 patients who were all analyzed on an intent-to-treat basis. Median follow-up of all patients was 27 months. One patient progressed and died before treatment, and five patients died during treatment. Four patients received RT after one cycle of chemotherapy, and 42 patients completed the entire treatment. Hematologic grade 3 and 4 toxicity was seen in 78% of patients for leukocytes and 24% of patients for platelets. The overall response rate of all 52 patients was 81%. Two patients who did not fulfill the criteria of objective response survived more than 1 year; one of them is still alive without disease. Eighteen patients died; 11 deaths were a result of tumor, five were probably treatment-related, one was caused by late leukoencephalopathy, and one was a result of intercurrent disease. Median estimated overall survival was 46 months. Conclusion: MBVP followed by RT for PCNSL has a high response rate. However, the 10% toxic death rate during treatment in a multicenter setting underlines the need for highly specialized care.

Primary Central Nervous System Lymphoma: Results of a Pilot and Phase II Study of Systemic and Intraventricular Chemotherapy With Deferred Radiotherapy

2003 ◽  
Vol 21 (24) ◽  
pp. 4489-4495 ◽  
Author(s):  
Hendrik Pels ◽  
Ingo G.H. Schmidt-Wolf ◽  
Axel Glasmacher ◽  
Holger Schulz ◽  
Andreas Engert ◽  
...  
Keyword(s):  
Median Survival ◽  
Phase Ii ◽  
Response Rate ◽  
Phase Ii Study ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Response Duration ◽  
Cns Lymphoma ◽  
High Dose ◽  
Intraventricular Chemotherapy

Purpose: To evaluate response rate, response duration, overall survival (OS), and toxicity in primary CNS lymphoma (PCNSL) after systemic and intraventricular chemotherapy with deferred radiotherapy. Patients and Methods: From September 1995 to July 2001, 65 consecutive patients with PCNSL (median age, 62 years) were enrolled onto a pilot and phase II study evaluating chemotherapy without radiotherapy. A high-dose methotrexate (MTX; cycles 1, 2, 4, and 5) and cytarabine (ARA-C; cycles 3 and 6)–based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ARA-C. Results: Sixty-one of 65 patients were assessable for response. Of these, 37 patients (61%) achieved complete response, six (10%) achieved partial response, and 12 (19%) progressed under therapy. Six (9%) of 65 patients died because of treatment-related complications. Follow-up is 0 to 87 months (median, 26 months). The Kaplan-Meier estimates for median time to treatment failure (TTF) and median OS were 21 months and 50 months, respectively. For patients older than 60 years, median survival was 34 months, and the median TTF was 15 months. In patients younger than 61 years, median survival and median TTF have not been reached yet; the 5-year survival fraction is 75%. Systemic toxicity was mainly hematologic. Ommaya reservoir infection occurred in 12 patients (19%), and permanent cognitive dysfunction possibly as a result of treatment occurred in only two patients (3%). Conclusion: Primary chemotherapy based on high-dose MTX and ARA-C is highly efficient in PCNSL. Response rate and response duration in this series are comparable to the response rates and durations reported after combined radiotherapy and chemotherapy. Neurotoxicity was infrequent.

scholarly journals Phase II Trial of Temsirolimus for Relapsed/Refractory Primary CNS Lymphoma

2016 ◽  
Vol 34 (15) ◽  
pp. 1757-1763 ◽  
Author(s):  
Agnieszka Korfel ◽  
Uwe Schlegel ◽  
Ulrich Herrlinger ◽  
Martin Dreyling ◽  
Christian Schmidt ◽  
...  
Keyword(s):  
Phase Ii ◽  
Single Agent ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Weekly Dose

Purpose In this phase II study (NCT00942747), temsirolimus was tested in patients with relapsed or refractory primary CNS lymphoma (PCNSL). Patients and Methods Immunocompetent adults with histologically confirmed PCNSL after experiencing high-dose methotrexate-based chemotherapy failure who were not eligible for or had experienced high-dose chemotherapy with autologous stem-cell transplant failure were included. The first cohort (n = 6) received 25 mg temsirolimus intravenously once per week. All consecutive patients received 75 mg intravenously once per week. Results Thirty-seven eligible patients (median age, 70 years) were included whose median time since their last treatment was 3.9 months (range, 0.1 to 14.6 months). Complete response was seen in five patients (13.5%), complete response unconfirmed in three (8%), and partial response in 12 (32.4%) for an overall response rate of 54%. Median progression-free survival was 2.1 months (95% CI, 1.1 to 3.0 months). The most frequent Common Toxicity Criteria ≥ 3° adverse event was hyperglycemia in 11 (29.7%) patients, thrombocytopenia in eight (21.6%), infection in seven (19%), anemia in four (10.8%), and rash in three (8.1%). Fourteen blood/CSF pairs were collected in nine patients (10 pairs in five patients in the 25-mg cohort and four pairs in four patients in the 75-mg cohort). The mean maximum blood concentration was 292 ng/mL for temsirolimus and 37.2 ng/mL for its metabolite sirolimus in the 25-mg cohort and 484 ng/mL and 91.1 ng/mL, respectively, in the 75-mg cohort. Temsirolimus CSF concentration was 2 ng/mL in one patient in the 75-mg cohort; in all others, no drug was found in their CSF. Conclusion Single-agent temsirolimus at a weekly dose of 75 mg was found to be active in relapsed/refractory patients with PCNSL; however, responses were usually short lived.

Combined Immunochemotherapy With Reduced Whole-Brain Radiotherapy for Newly Diagnosed Primary CNS Lymphoma

2007 ◽  
Vol 25 (30) ◽  
pp. 4730-4735 ◽  
Author(s):  
Gaurav D. Shah ◽  
Joachim Yahalom ◽  
Denise D. Correa ◽  
Rose K. Lai ◽  
Jeffrey J. Raizer ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Karnofsky Performance Score ◽  
Whole Brain ◽  
Reduced Dose ◽  
Brain Radiotherapy

Purpose Our goals were to evaluate the safety of adding rituximab to methotrexate (MTX)-based chemotherapy for primary CNS lymphoma, determine whether additional cycles of induction chemotherapy improve the complete response (CR) rate, and examine effectiveness and toxicity of reduced-dose whole-brain radiotherapy (WBRT) after CR. Patients and Methods Thirty patients (17 women; median age, 57 years; median Karnofsky performance score, 70) were treated with five to seven cycles of induction chemotherapy (rituximab, MTX, procarbazine, and vincristine [R-MPV]) as follows: day 1, rituximab 500 mg/m2; day 2, MTX 3.5 gm/m2 and vincristine 1.4 mg/m2. Procarbazine 100 mg/m2/d was administered for 7 days with odd-numbered cycles. Patients achieving CR received dose-reduced WBRT (23.4 Gy), and all others received standard WBRT (45 Gy). Two cycles of high-dose cytarabine were administered after WBRT. CSF levels of rituximab were assessed in selected patients, and prospective neurocognitive evaluations were performed. Results With a median follow-up of 37 months, 2-year overall and progression-free survival was 67% and 57%, respectively. Forty-four percent of patients achieved a CR after five or fewer cycles, and 78% after seven cycles. The overall response rate was 93%. Nineteen of 21 CR patients received the planned 23.4 Gy WBRT. The most commonly observed grade 3 to 4 toxicities included neutropenia (43%), thrombocytopenia (36%), and leukopenia (23%). No treatment-related neurotoxicity has been observed. Conclusion The addition of rituximab to MPV increased the risk of significant neutropenia requiring routine growth factor support. Additional cycles of R-MPV nearly doubled the CR rate. Reduced-dose WBRT was not associated with neurocognitive decline, and disease control to date is excellent.

Immuno-Chemotherapy with Rituximab, Methotrexate, Lomustine, and Procarbazine for the Treatment of Primary CNS Lymphoma in Patients >65 Years.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3712-3712
Author(s):  
Kristina Fritsch ◽  
Benjamin Kasenda ◽  
Anna Markert ◽  
Jürgen Finke ◽  
Gerald Illerhaus
Keyword(s):  
Elderly Patients ◽  
Conflicts Of Interest ◽  
Alkylating Agents ◽  
Objective Response ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Karnofsky Performance Score

Abstract Abstract 3712 Poster Board III-648 Introduction Primary central nervous system lymphoma (PCNSL) is an aggressive extranodal non-Hodgkin lymphoma (NHL) confined to the CNS and/or eyes at presentation. PCNSL have a poor prognosis dispite good initial response to steroids and whole brain irradiation (WBRT). Addition of high-dose methotrexate (MTX) to therapy has improved the prognosis of patients with PCNSL, resulting in median survival rates of up to 60 months (mo). However, most patients eventually relapse. Surviving patients, particularly elderly treated with combined radio-chemotherapy are at substantial risk of developing leukoencephalopathy. We developed a protocol with high-dose MTX combined with the lipophilic alkylating agents procarbacine and lomustine and the anti-CD20 monoclonal antibody rituximab (R-MPL protocol), especially adapted for elderly patients with PCNSL. Here we report the results of 28 patients treated with combined immuno-chemotherapy with R-MPL protocol within a monocentric study. Methods Patients ≥65 yrs with PCNSL were treated with up to 3 cycles of R-MPL protocol: rituximab (375mg/m2 d-6, 1, 15, 29), MTX (3g/m2 d2, 16, 30), procarbazine (60 mg/m2 p.o., d1-10) and lomustine (110 mg/m2 p.o., d1). Cycles were repeated d42. Inclusion criterias were age ≥65 yrs and biopsy proven PCNSL. There was no lower limit of Karnofsky Performance Score. Results 28 patients (median age 75 yrs., range 65-83 yrs.) received R-MPL protocol. 2 patients died, one due to pulmonary embolism 2 weeks after initiation of treatment, the other had a perforation of the sigmoid and both were not evaluable for response. Objective response was seen in 25 of 26 patients (96,2%) with 19 CR and 6 PR. In 5 patients, MTX was not tolerated after 1 (n=4) and 2 (n=1) applications due to cholestatic hepatitis (n=1) and renal impairment (n=4). 2 patients with refractory disease could successfully be salvaged with AraC/thiotepa (n=1) and HDT and ASCT (n=1), respectively. 5 patients experienced relapse and could not be salvaged. After a median follow-up of 26 mo (range 2-35) 10 patients (35,7 %) are alive and disease-free. By intend-to-treat-analysis the 12-mo and 24-mo is 69% and 52% respectively. Severe leukoencephalopathy has not been observed. Most recent follow-up data will be presented in detail. Conclusion The immuno-chemotherapy protocol presented here is safe and shows high efficacy in treating elderly patients with PCNSL. A prospective phase-II trial will be initiated. Disclosures: No relevant conflicts of interest to declare.

scholarly journals HDMTX-based polychemotherapy including intraventricular therapy in elderly patients with primary CNS lymphoma: a single center series

2020 ◽  
Vol 13 ◽  
pp. 175628642095108
Author(s):  
Sabine Seidel ◽  
Thomas Kowalski ◽  
Michelle Margold ◽  
Alexander Baraniskin ◽  
Roland Schroers ◽  
...  
Keyword(s):  
Complete Remission ◽  
Elderly Patients ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Cerebrospinal Fluid Leak ◽  
Ommaya Reservoir ◽  
Cns Lymphoma ◽  
High Dose ◽  
Karnofsky Performance Score

Background: To investigate outcome and toxicity of high-dose systemic methotrexate (HDMTX)-based polychemotherapy and intracerebroventricular (ICV) chemotherapy via an Ommaya reservoir in elderly patients with primary central nervous system lymphoma (PCNSL). Methods: We performed a retrospective analysis on patients ⩾65 years with first diagnosis of PCNSL admitted to our center between January 2015 and December 2019. These patients were treated with a standardized chemotherapy protocol in case of absent contraindications for HDMTX-based chemotherapy. The protocol contained induction therapy with systemic rituximab, methotrexate and ifosfamide and consolidation treatment with systemic cytarabine (AraC) and ICV methotrexate, prednisolone and AraC. Results: Of a total of 46 patients seen in this period, 3 did not qualify for HDMTX. Thus, 43 patients were included in this analysis. Median age was 74 years (range 65–86), median Karnofsky performance score was 50 (range 20–90). Of the 43 patients, 32 (74.4%) completed treatment including ICV therapy. Complete remission/complete remission unconfirmed was achieved in 26 of 43 patients (60.5%), partial response (PR) in 3 (7%); 5 (11.6%) had progressive disease, and 3 (7.0%) died due to treatment-related complications; in the remaining 6 (14.0%) therapy could not be completed. Median progression free survival was 16 months (95% confidence interval 8–24 months) and median overall survival had not been reached after a median follow up of 23 months (range 1–52 months); the 75th percentile survival time was 12 months. No Ommaya reservoir infection was observed. Complications of ICV treatment were pericatheter leucencephalopathy in two patients and surgical scar dehiscence with cerebrospinal fluid leak in one patient. Conclusion: Toxicity of HDMTX plus ICV chemotherapy for elderly patients with PCNSL was manageable and outcome was excellent for patients treated with this protocol.

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

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.

First Results of the Acsé Pembrolizumab Phase II in the Primary CNS Lymphoma (PCNSL) Cohort

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Khe Hoang-Xuan ◽  
Roch Houot ◽  
Carole Soussain ◽  
Marie Blonski ◽  
Anna Schmitt ◽  
...  
Keyword(s):  
Objective Response ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Cns Lymphoma ◽  
High Dose ◽  
Moderate Activity ◽  
Multicentric Study ◽  
First Results ◽  
Duration Of Response

Background: AcSé Pembrolizumab is a Phase 2, open-label, single-arm, multi-cohort, multicentric study investigating the efficacy and safety of pembrolizumab monotherapy in patients with advanced rare cancers (NCT03012620). Here, we report the first results of Pembrolizumab in the cohort of Primary Central Nervous System Lymphoma (PCNSL). Methods: Main inclusion criteria were: relapsed or refractory PCNSL after one or several lines of treatment including high dose Methotrexate based chemotherapy, pathologically confirmed diffuse large B cell lymphoma, age>18, HIV negative, concurrent steroid medication at a dose no greater than prednisone 20 mg/day or equivalent. Patients received pembrolizumab 200 mg IV as a 30-minute infusion on Day 1 of every 21-day cycles for a maximum of 2 years. The primary endpoint was the confirmed objective response rate according to IPCG at 84 day after the start of treatment. Secondary endpoints included best response (ORR), duration of response, progression-free survival (PFS), overall survival (OS), and safety. Analysis used all enrolled patients. Results: 50 patients suffering from PCNSL, including 9 primary vitreoretinal lymphoma (PVRL) were included from July, 2017 to October, 2019. Median age was 72 years (range: 43 to 83), Median PS (ECOG) was 1 (range 0-1). The median number of cycles was 4 (range 1-35). At 84 days from start of treatment, 6 patients responded (4 CR+2PR). Overall, 3 patients whose response was not assessed were considered as failures, and the rates of ORR (CR+PR), stable disease (SD), progressive disease (PD) were 26% (13/50, 8 CR + 5 PR), 10% (5/50), 58% (29/50), respectively. ORR was 29% (12/41) and 11% (1/9) in primary cerebral lymphoma and PVRL respectively. After a median follow-up of 6.7 months (range 0.2-27.4), median PFS was 2.6 months, with 6-month PFS of 29.8% and 6-month OS of 60.4%. In responders, median duration of response was estimated at 10 months (95%CI, 2.7 to 12.5). Grade III and IV toxicities related to the drug were observed in 4 patients (8%) and one patient (2%) respectively. No related toxic death was reported. Conclusion: Pembrolizumab shows moderate activity in relapsed/ refractory PCNSL with acceptable toxicity, supporting further studies evaluating its use in combination therapies. Disclosures Hoang-Xuan: BTG: Consultancy, Research Funding. Houot:Bristol-Myers Squibb: Honoraria; MSD: Honoraria; Gilead: Honoraria; Kite: Honoraria; Roche: Honoraria; Novartis: Honoraria; Janssen: Honoraria; Celgene: Honoraria. Schmitt:Celgene: Membership on an entity's Board of Directors or advisory committees; Roche, Janssen: Honoraria. Ahle:Roche: Honoraria; Novartis: Honoraria; Biogene: Honoraria; Abbvie: Honoraria; Sanofi: Honoraria. Bories:Abbvie: Consultancy; Celgen: Consultancy; Gilead: Consultancy; BMS: Honoraria; Novartis: Honoraria. Houillier:BTG: Consultancy.

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