A single centre study of the treatment of relapsed primary central nervous system lymphoma (PCNSL) with single agent temozolomide

2012 ◽  
Vol 19 (11) ◽  
pp. 1501-1505 ◽  
Author(s):  
S.F. Wong ◽  
H.K. Gan ◽  
L. Cher
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
Single Centre ◽  
Centre Study ◽  
Single Centre Study

scholarly journals Efficacy and Toxicity of Treatments for Primary Central System Lymphoma: Review of the Recent Literature

2019 ◽  
Vol 9 (1) ◽  
pp. 61-67
Author(s):  
Mohammad Jay ◽  
David. A. MacDonald
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Survival Benefit ◽  
Radiation Treatment ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Cell Transplant ◽  
Wide Range

Primary Central Nervous system lymphoma (PCNSL) is an uncommon type of central nervous system lymphoma, most commonly presenting as hemiparesis and headache. Currently, there is a wide range of treatments for PCNSL, consisting of various permutations between chemotherapy, radiation and autologous stem cell transplant (ASCT). Although the backbone of PCNSL treatment consists of High-dose Methotrexate (HD-MTX), the role of combination versus single agent chemotherapy, combined modality (chemotherapy + radiation) versus chemotherapy or radiation alone, and the use of consolidative ASCT are contested. Surgery does not have a role in the treatment of PCNSL although stereotactic biopsies tend to help with symptomatic relief. Radiation monotherapy is generally reserved for patients with contraindications to chemotherapy or as a palliative measure. Combined chemotherapy and radiation treatment has been shown to have a great efficacy, although its increased neurotoxicity compared to chemotherapy alone is a major drawback. A growing body of research is focused on comparing the efficacy of various chemotherapeutic regimens. Currently, the MATRix regimen comprising of HD-MTX(3.5g/m2)-cytarabine/rituximab/thiotepa is widely used. The additional survival benefit of ASCT is contested although its role in the treatment of refractory or relapsed PCNSL is generally agreed upon. Finally, intrathecal HD-MTX has been shown to have added survival benefit when added to the standard therapies. Further retrospective and prospective studies are required to compare the efficacy and toxicity of various treatment options, with a focus on different chemotherapeutic agents and ASCT.

scholarly journals Ibrutinib in patients with relapsed/refractory central nervous system lymphoma: A retrospective single‐centre analysis

2020 ◽  
Vol 190 (2) ◽  
Author(s):  
Eliza M. Lauer ◽  
Miguel Waterhouse ◽  
Moritz Braig ◽  
Jurik Mutter ◽  
Sabine Bleul ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
Single Centre

What Is The Optimal Dose Of Methotrexate In Primary Central Nervous System Lymphoma Treatment Regimens?

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3040-3040
Author(s):  
Samir Dalia ◽  
Samantha L Price ◽  
Peter Forsyth ◽  
Celeste M. Bello ◽  
Bijal D. Shah ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Total Dose ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
Chemotherapeutic Agents ◽  
High Dose ◽  
Significant Difference ◽  
Treatment Data ◽  
Dose Reductions

Abstract Introduction Primary central nervous system lymphoma (PCNSL) is a rare disorder with a poor prognosis. The mainstay of treatment is single agent or combination high dose (≥3.5g/m2) methotrexate (HDMTX) based regimens. There is no consensus as to which dose of HDMTX improves outcomes in patients with PCNSL but doses of MTX greater than 3 g/m2 intravenously achieve therapeutic cerebrospinal fluid (CSF) concentrations. Purpose To determine if there is an optimal or total dose of HDMTX in PCNSL therapies that results in improved progression free (PFS) or overall survival (OS). Methods Patients at Moffitt Cancer Center with PCNSL were identified using our institutional database between January 1, 2000 and September 30, 2011. Patients with complete treatment data who were treated with HDMTX were included in this study. HDMTX was defined as MTX at a dose ≥ 3.5g/m2. Patient demographics, clinical, and treatment data were collected and analyzed. Treatment information collected included the starting dose of HDMTX, IV rituximab use, MTX toxicity and clearance, cycles of MTX, and total amount of MTX administered (g/m2). Data were analyzed using descriptive statistics and the Kaplan-Meier (KM) method was used to estimate median PFS and OS using the log rank test. P value of <0.05 was considered significant. All data was analyzed using SPSS statistical software version 21.0. Results A total of 51 patients were identified (Table 1). Median PFS was 13months (0-33) and median OS 43months (29-57). The addition of IV rituximab or other chemotherapy failed to improve PFS or OS. HDMTX dose reductions or the total dose of HDMTX administered did not significantly impact PFS or OS. Similarly, when comparing dosing of HDMTX there was no significant difference in 8g/m2 versus 3.5g/m2 (PFS p=0.56, OS p=0.68), or between patients receiving 8g/m2 versus <8g/m2 (PFS p=0.77, OS p=0.6) (Figure 1). Patients receiving 8g/m2 versus those receiving <8g/m2 of HDMTX had similar baseline characteristics except for more liver function abnormalities in the 8g/m2 group. Conclusions Differences in initial dosing of HDMTX or total dose of HDMTX therapy did not influence outcomes in our patients with PCNSL. Dose reductions in HDMTX, addition of other chemotherapeutic agents, or rituximab were not associated with improved PFS or OS. An intriguing plateau was observed in OS in the 8gm/m2 arm despite similar PFS, suggesting that the receipt of novel therapies in the relapsed setting may contribute to OS. Multicenter collaborative clinical trials are needed to further assess the optimal initial dose of HDMTX to administer in PCNSL. Disclosures: No relevant conflicts of interest to declare.

scholarly journals LINC-33. MULTIMODALITY MANAGEMENT OF PAEDIATRIC PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA- UPDATED EXPERIENCE FROM A REGIONAL CANCER CENTRE IN NORTH INDIA

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii385-iii385
Author(s):  
Ahitagni Biswas ◽  
Swarnaditya Roy ◽  
Yousra KN ◽  
Sameer Bakhshi ◽  
Vaishali Suri ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
North India ◽  
High Dose ◽  
Ocular Involvement ◽  
Csf Cytology ◽  
Whole Brain ◽  
Female Ratio

Abstract Paediatric primary central nervous system lymphoma(PCNSL) constitutes 1% of all PCNSLs. Data pertaining to paediatric PCNSL (2016–19) was abstracted by retrospective chart review. We identified 7 paediatric patients with PCNSL. None had congenital or acquired immunodeficiency. The median age at presentation was 13 years. The male to female ratio was 4:3. The median ECOG performance status was 2. On neuro-imaging, 3 patients had solitary and 4 patients had multiple lesions. CSF cytology showed atypical cells in 1 patient. None had ocular involvement. Systemic lymphoma work-up was negative in all. Biopsy and resection of tumour were done in 4 patients each. Histopathology revealed DLBCL in 6 and B-cell NHL in 1 patient. All patients underwent induction chemotherapy (median-5 cycles)- modified DeAngelis protocol (IV Methotrexate-2.5g/m2,IT Methotrexate-12 mg,Vincristine,Procarbazine and Rituximab-375mg/m2 every 2 weeks) in 6 and single agent Methotrexate -3.5g/m2 every 3 weeks in 1 patient. Severe haematological toxicities included grade 3 neutropenia, leucopenia and febrile neutropenia in 2,1 and 1 patient respectively. Radiotherapy(RT) was administered in all-whole brain RT(36-45Gy/20-25fractions/4-5weeks) in 6 patients and craniospinal RT(36Gy/18fractions/3.5weeks) followed by whole brain RT(9Gy/5fractions/1week) in 1 patient(with positive CSF cytology). Subsequently consolidation chemotherapy with 2 cycles of Cytarabine(3g/m2 IV D1-2 every 3 weeks) was administered in 5 patients. After a median follow-up of 14 months(mean-18.2 months), all patients are in complete radiological remission. Paediatric PCNSL is a rare tumour entity and multimodality management with high dose Methotrexate and Rituximab based chemo-immunotherapy and cranial radiotherapy leads to excellent early clinical outcome.

scholarly journals Real-World Outcomes of Older Patients with Primary Central Nervous System Lymphoma (PCNSL): Methotrexate Dose Intensity and Combination with Cytarabine Correlate with Response and Survival

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 572-572
Author(s):  
Nicolas Martinez-Calle ◽  
Edward Poynton ◽  
Alia Alchawaf ◽  
Shireen Kassam ◽  
Matthew Horan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Central Nervous System ◽  
Nervous System ◽  
Median Time ◽  
Real World ◽  
Research Funding ◽  
Single Agent ◽  
Dose Intensity ◽  
Central Nervous System Lymphoma ◽  
Support Research

Abstract INTRODUCTION Primary central nervous system lymphoma (PCNSL) in patients (pts) over 65 years old have poorer outcome compared to younger cohorts, as comorbidities, baseline performance status and susceptibility to iatrogenic toxicity impede adequate drug delivery (Kasenda et al, Ann Oncol, 2015). Balancing toxicity against treatment benefits remains a challenge in this age group. Recent trials have attempted to rationalize treatment aiming for reduced toxicity whilst maintaining CNS penetration. Efficacy of additional agents, such as oral alkylators (Fritsch et al, Leukemia 2017) has also been demonstrated. Most clinical trial cohorts underrepresent elderly pts and thus analysis of real-world outcomes and therapeutic practice is warranted. METHODS Consecutively diagnosed pts between 01/10/12 and 01/10/17, ≥65 years old in 14 tertiary UK centres were analysed retrospectively. Radiological exclusion of systemic disease and histological diagnosis were mandatory. Pts receiving any form of 1st line treatment including palliative (whole-brain radiotherapy [WBRT]/oral chemotherapy), best supportive care (BSC) or clinical trial were included. Diagnostic and referral pathways were audited. Baseline patient characteristics and treatment received was recorded in order to document current UK practice. Pts. were stratified into 4 treatment groups: single agent MTX; MTX with oral alkylator; high-intensity HI-MTX (MTX/AraC and MATRix) or palliative intent treatment (WBRT/oral alkylator/BSC). The study primary outcome was overall response rate (ORR) after induction. Secondary outcomes were PFS and OS. Additional variables were MTX clearance and the relative dose intensity (RDI) of MTX normalised with a reference of 14mg/m2. UV/MVA for ORR and Cox-regression for PFS and OS were used for identification of baseline predictors of response and survival. RESULTS 244 pts were included in the analysis with median age 71yrs (range 65-91) and 123 (50%) male. LDH (Elevated:104, 42%) and ECOG performance score (PS) (3-4: 87, 36%) were the only prognostic markers recorded. Median time from presenting scan to treatment was 33 days (IQR 22-48). Demographic characteristics are summarised in table 1. 80% of pts (n=192) received MTX based chemotherapy. 68% of pts >70yr and 50% >75yr received >1 cycle of MTX. MTX median cumulative dose delivered was 10.6 g/m2 (range 1.5-21), median number of cycles was 4 (range 1-6). Dose reductions of MTX occurred in 53/176 pts. (30%). Median time to MTX clearance was 3 days (range 1-18) and median RDI was 0.75 (range 0.11-1.5). TRM for MTX treated pts was 7.2%. 112 pts received rituximab (46%; 11% pre-2015 vs. 64% post-2015). 73 pts. (38%) received <2 cycles of treatment, reasons for dropout were progression (49/73), chemotherapy-related adverse events (13/73) and unknown (11/66); median OS for these pts was 4.1 months. 66 pts received consolidation (15 WBRT, 36 ASCT and 13 oral alkylator) with a median age of 69 (range 65-84). Median OS in this group was 64 months. ORR after induction was 63%. HI-MTX (HR 3.4; CI 95% 1.5 - 7.6; p=0.003) was independently associated with superior ORR compared to HD-MTX alone (Table 1). Median follow up for survival was 25 months. 2-yr PFS and OS were both 39%, median OS after progression was 80 days. MTX RDI (HR 0.18; p<0.001) was the only independent covariate for PFS. Treatment allocation to HI-MTX (HR 0.47; p=0.02), MTX RDI (HR 0.23; p=0.001) and complete response following induction (HR 0.29; p=0.001) were covariates for OS. 52 pts (21%) received upfront palliative treatment and compared to MTX cohort, were older (median 76y vs. 70y), had a poorer PS (ECOG 3-4: 62% vs. 28%) and higher incidence of impaired renal function (GFR < 60ml/min: 15% vs. 5%). CONCLUSION MTX can be delivered to the majority of pts >70 years with manageable TRM rates. Notably, early treatment discontinuation was relatively frequent with outcomes in this group comparable to palliative care. By contrast, pts who completed >3 cycles of HI-MTX and underwent consolidation experienced comparable outcomes to younger trial cohorts. MTX combination chemotherapy and MTX dose intensity were the strongest predictors of survival whilst rituximab was not a covariate for response or survival despite an increase in its use. Maximising cumulative MTX dose, particularly within more intensive protocols, may translate into improved ORR and survival in older pts with PCNSL. Table. Table. Disclosures Kassam: AbbVie: Equity Ownership. Culligan:Merck Sharp & Dohme (MSD): Honoraria; Celgene: Other: Support to attend conferences; Daiichi-Sankyo: Other: Support to attend conferences; JAZZ: Honoraria; Abbvie: Other: Support to attend conferences; Takeda: Honoraria, Other: Support to attend conferences; Pfizer: Honoraria. McKay:Epizyme: Consultancy, Honoraria. Eyre:Roche: Consultancy; Janssen: Consultancy, Other: travel support; Gilead: Consultancy, Other: travel support; Abbvie: Consultancy, Other: travel support; Celgene: Other: travel support. Osborne:Roche: Consultancy, Honoraria, Speakers Bureau; Pfizer: Honoraria, Speakers Bureau; Servier: Consultancy; MSD: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Honoraria, Speakers Bureau; Novartis: Other: Travel to conference. Yallop:Servier: Other: Travel funding; Pfizer: Consultancy. Fox:Janssen: Consultancy, Other: Personal fees and non-financial support, Speakers Bureau; AbbVie: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; Celgene: Consultancy, Other: Travel support, Speakers Bureau; Sunesis: Consultancy; Roche: Consultancy, Other: Travel support, Research Funding, Speakers Bureau; Gilead: Consultancy, Other: Travel support, Research Funding, Speakers Bureau. Cwynarski:Roche: Consultancy, Other: Conferences/Travel support, Speakers Bureau; Autolus: Consultancy; Kite: Consultancy; Gilead: Consultancy, Other: Conferences/Travel support, Speakers Bureau; Janssen: Other: Conferences/Travel support.

Chemotherapy for primary central nervous system lymphoma

2006 ◽  
Vol 21 (5) ◽  
pp. 1-8 ◽  
Author(s):  
Antonio M. P. Omuro ◽  
Lauren E. Abrey
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Randomized Trials ◽  
Single Agent ◽  
Central Nervous System Lymphoma ◽  
High Dose ◽  
Dose Methotrexate ◽  
Intensified Chemotherapy ◽  
Relapse Rates

✓Chemotherapy, with or without radiotherapy, is the mainstay of treatment for primary central nervous system lymphoma (PCNSL). High-dose methotrexate (MTX) is the most effective drug available to treat these lesions, and it is used in doses of 1 to 8 g/m2, either as a single agent or in combination with other drugs such as corticosteroid agents, cytarabine, procarbazine, vincristine, carmustine, lomustine, thiotepa, cyclophosphamide, temozolomide, and rituximab. To date, an overwhelming number of different regimens in which high-dose MTX is used have been reported. Given the lack of randomized trials, however, the optimal treatment remains controversial. Varying methodology makes the comparison of available studies extremely difficult, yet some common themes can be found throughout the literature. Treatment paradigms vary considerably according to the patient's age. Most studies support the use of chemotherapy-only treatments for elderly patients (> 60 years), given the high risks of neurotoxicity associated with radiotherapy. Nevertheless, the prognosis remains poor regardless of the chemotherapy chosen, and less toxic regimens might be preferable for such elderly patients. Conversely, in younger patients (< 60 years), there is growing evidence that commonly used chemotherapy-only regimens are associated with increased relapse rates that may not justify deferral of radiotherapy. Thus, a significant focus of research has been the development of intensified chemotherapy regimens that could replace radiotherapy. In this article, the authors discuss the principles guiding the use of chemotherapy for PCNSL, and critically review the available literature, including the most recent trials.

Ibrutinib-based combination therapy exhibited therapeutic benefit in newly diagnosed primary central nervous system lymphoma.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2556-2556
Author(s):  
Feili Chen ◽  
Diwen Pang ◽  
Hanguo Guo ◽  
Qiuxiang Ou ◽  
Xue Wu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Combination Therapy ◽  
De Novo ◽  
Single Agent ◽  
Objective Response ◽  
Central Nervous System Lymphoma ◽  
High Dose ◽  
Induction Phase ◽  
Newly Diagnosed

2556 Background: Ibrutinib has shown single-agent activity in relapse/refractory (R/R) primary central nervous system lymphoma (PCNSL), and the high dose methotrexate (HD-MTX) has been the backbone of treatment of de-novo PCNSLs. Combination therapy of HD-MTX and ibrutinib has recently shown activity in R/R PCNSLs. Methods: Eleven newly diagnosed PCNSL patients who underwent combination therapy of HD-MTX and ibrutinib were analyzed for treatment response and safety profile. HD-MTX was given at 3.5 g/m2 every 2 weeks for a total of 8 doses. Ibrutinib was held on days of HD-MTX infusion until HD-MTX clearance. Single-agent daily ibrutinib was administered continuously after completion of induction therapy until disease progression, intolerable toxicity, or death. Patients’ clinicopathologic characteristics were retrospectively reviewed and genomic traits were further analyzed. Results: Nine out of 11 patients have completed the induction phase of ibrutinib-based combination therapy and received ibrutinib maintenance in addition to two patients whose disease progressed during the therapy. An objective response rate (ORR) of 82% (9/11) was observed, including 7 patients with complete response (CR, 64%) and 2 patients with partial response (PR, 18%). The median progression-free survival (PFS) was 7.4 months while the median overall survival (OS) was not reached. The combination therapy of HD-MTX and ibrutinib was well tolerated and has acceptable safety. In addition, the presence of ctDNA in cerebrospinal fluid (CSF) samples closely correlated with tumor response. Sustained tumor responses were associated with the clearance of ctDNA from the CSF. Conclusions: Combination of ibrutinib and HD-MTX has acceptable safety and has demonstrated anti-tumor activity in newly diagnosed de-novo PCNSL patients. The detection of ctDNA in CSF is feasible for monitoring tumor burden in PCNSL patients.

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