Primary CNS lymphoma: A review of clinicopathologic characteristics, therapy, and outcomes of 54 patients with primary CNS DLBCL.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2099-2099
Author(s):  
Nalini Hasija ◽  
Michael Jaglal ◽  
Vu Duong ◽  
Celeste M. Bello ◽  
Michael B. Tomblyn ◽  
...  

2099 Background: Primary central nervous system lymphoma (PCNSL) is a rare aggressive variant of diffuse large B cell lymphoma (DLBCL) with a poor prognosis. Optimal therapeutic strategies have not yet been defined. High dose methotrexate (HD MTX) is an effective chemotherapeutic agent with superior outcomes compared to historical studies using whole brain radiation therapy (WBRT). Purpose: To review clinicopathologic characteristics, therapy and outcomes of 54 patients (pts) with primary CNS DLBCL. Methods: This was a single center retrospective review of pts with confirmed diagnosis of primary CNS DLBCL from 1999 to 2009. Data was extracted from the Moffitt Cancer Center (MCC) electronic records. Baseline demographics, clinical, pathological and treatment data were collected and analyzed. Pts were stratified according to their treatment regimens including HD MTX (8g/m2) alone or in combinations and WBRT alone or in combination with CT. Descriptive statistical analyses were utilized. Chi square analysis and t- test were performed to compare categorical and continuous variables. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the groups. All data was analyzed using SPSS version 20.0 statistical software. Results: 54 pts who underwent CT and/or WBRT for PCNSL between 1999 and 2009 were identified. The age range at diagnosis was 19-85 years with median age of 63. 31 of 54 pts (57%) were ≥ 60 years old. Male to female ratio was 1.25 :1 (30:24). The median ECOG PS was 1. Only 2 pts had HIV. A majority of pts presented with motor deficits. The most common location of lymphoma was in the cerebral hemispheres. The median survival of the entire cohort was 42 months. 15 of 54 pts (23%) survived ≥ 60 months. In the cohort of pts that survived ≥ 60 months, a majority 11 of 15 (73%) received HD MTX. Pts treated with initial WBRT revealed inferior overall survival (OS) compared to pts treated with induction CT (OS 37 months vs. 50 months) (p=0.056). Conclusions: HD MTX was the most frequently utilized CT regimen in the cohort of pts surviving > 60 months. Administering WBRT as an initial modality was associated with worse outcomes in this retrospective analysis.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4858-4858
Author(s):  
Michael V. Jaglal ◽  
Bijal D. Shah ◽  
Jennifer L. Cultrera ◽  
Eduardo M. Sotomayor ◽  
Michael B Tomblyn ◽  
...  

Abstract Abstract 4858 Background Primary central nervous system lymphoma (PCNSL) is a rare aggressive variant of diffuse large B cell lymphoma (DLBCL) with a poor prognosis. Optimal therapeutic strategies have not been defined yet in primary CNS lymphoma. High dose Methotrexate (HD MTX) is an effective chemotherapeutic agent with superior outcomes compared to historical studies using whole brain radiation therapy (WBRT). The combination of HD MTX with WBRT showed improved response rates compared to chemotherapy (CT) alone, but was associated with greater risk of neurotoxicity in patients >60 years old. Purpose To review clinicopathologic characteristics, therapy and outcomes of 59 patients with primary CNS DLBCL without HIV. Methods This was a single center retrospective review of pts with confirmed diagnosis of primary CNS DLBCL from 1999 to 2012. Data was extracted from the Moffitt Cancer Center (MCC) electronic records. Baseline demographics, clinical, pathological and treatment data were collected and analyzed. Patients were stratified according to their treatment regimens including HD MTX (3g/m2) alone or in combinations and WBRT alone or in combination with CT. Descriptive statistical analyses were utilized. Chi square analysis and t- test were performed to compare categorical and continuous variables. Kaplan-Meier method was used to estimate OS and log rank test was used to compare the groups. All data was analyzed using SPSS version 19.0 statistical software. Results 59 patients who underwent CT and/or WBRT for PCNSL between 1999 and 2012 were identified. The age range at diagnosis was 17–85 years with median age of 64. 35 of 59 patients (59%) were ≥ 60 years old. Male to female ratio was 1.27:1 (33:26). The median ECOG PS was 1. A majority of patients presented with motor deficits, 29 out of 59. The most common location of lymphoma was in the cerebral hemispheres. The median survival of the entire cohort was 37 months. 18 of 59 pts (25%) survived ≥ 60 months. In the cohort of pts that survived ≥ 60 months, a majority 16 of 18 (89%) received HD MTX. Patients treated with initial WBRT and chemotherapy revealed inferior overall survival (OS) compare to patients treated with induction chemotherapy alone (OS 37 months vs. 66 months) (p=0.011). Patients over the age of 60 had worse outcomes compared to patients who were less than the age of 60 (OS 33 months versus 70 months) (p=0.023). Conclusions HD MTX was the most frequently utilized CT regimen in the cohort of patients surviving > 60 months. Administering WBRT combined with chemotherapy was associated with worse outcomes in this retrospective analysis. Patients with primary CNS lymphoma who are older than 60 have worse outcomes in this retrospective analysis compared to patients younger than 60. Disclosures: Sokol: Celgene: Honoraria, Speakers Bureau.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 16-17
Author(s):  
Cesar Gentille Sanchez ◽  
Ethan Burns ◽  
Ibrahim Muhsen ◽  
Humaira Sarfraz ◽  
Carlo Guerrero ◽  
...  

Introduction Primary Central Nervous System Lymphoma (PCNSL) is a rare form of extra-nodal non-Hodgkin Lymphoma (NHL), with diffuse large B-cell Lymphoma (DLBCL) reported in 90% of cases. Secondary CNS lymphoma (SCNSL) may occur as an isolated recurrence of previously diagnosed NHL or occur simultaneously as a manifestation of systemic disease. Comparative data on survival in treated PCNSL and SCNSL in the real-world setting is lacking. We present a retrospective analysis of outcomes in PCNSL and SCNSL patients treated at the Houston Methodist Cancer Center. Methods We retrospectively identified patients with a diagnosis of PCNSL or SCNSL from 2015 to 2020. Data collected included age, race, sex, diagnosis (PCNSL, SCNSL), histology and immunohistochemistry, treatment type (chemotherapy, radiation), transplant rates as well as outcomes (alive/dead). Responses were classified as complete response (CR), partial response (PR), stable disease (SD) and progressive disease (PD). Survival was analyzed using Kaplan-Meier methodology, and log-rank tests were used to compare survival distributions. P < 0.05 was considered statistically significant. Results There were 50 patients with CNS lymphoma identified between 2015 and 2020; 68% were PCNSL. Out of 43 with available pathology, 2 patients were T-cell lymphomas and 41 DLBCL. Out of the DLBCL cases, 95% of cases expressed CD20 while close to 60% were positive for MUM1, bcl-2 and bcl-6. Less than 15% of cases were positive for CD10. CD30 was positive in 17% of cases. Cerebral hemispheres (76%) was the most common organ involved, followed by ocular (8%), intraventricular space (6%) and cerebellum (6%). Median age at diagnosis was 67 years; male to female ratio was 1.27. Caucasian (62%) and Hispanic (24%) were most common ethnicities. Epstein-Barr Virus was positive in 14% of patients (5 in PCNSL and 2 in SCNSL). One patient with SCNSL had human immunodeficiency virus. The median follow-up time was 9.1 months. Multiagent chemotherapy including high dose methotrexate (MTX), cytarabine and rituximab was given to 48% of the patients while 32% received high dose MTX alone plus rituximab. From the latter group, five out of sixteen patients received temozolomide. Other regimens were used in 6% of the cases. Median dose of MTX in a multiagent chemotherapy regimen was 2.5gr/m2 and 2.25gr/m2 when used alone or with temozolomide. Median number of cycles given was 3. Radiation therapy alone was given to 8% of cases. Three patients did not receive treatment. For patients with PCNSL, overall response rate (ORR) was 82.8% (CR 65.5%, PR 13.8%, SD 3.4%). ORRs were similar between multiagent chemotherapy and methotrexate alone (+/- temozolomide) with 86.7% and 83.3% respectively. ORR for SCNSL was 57.1% (CR 35.7%, PR 21.4%); only 1 patient was treated with MTX alone. Further lines of therapy were required in 9.3% of patients. Consolidation with whole brain radiation was given in 22% of the cases (29.4% for PCNSL and 6.3% for SCNSL). Autologous stem cell transplant was performed in 10% of the patients (2 PCNSL, 3 SCNSL). Overall survival for patients with PCNSL was 74.8 months and 10.1 months for SCNSL (p=0.0444) (Figure 1). Survival was not significant between patients receiving multiagent chemotherapy and MTX alone or in combination with temozolomide (3-year OS 57.3% vs 73.4%, p= 0.5652) (Figure 2). Conclusion Most patients diagnosed with PCNSL are non-germinal center DLBCL. Median MTX dose was lower than 3gr/m2 with excellent ORR of over 80% in PCNSL. Response rates were lower in SCNSL and in general, patients with PCNSL had better outcomes. Survival did not differ significantly between regimens, suggesting that a lower intensity therapy may perform similarly to multiagent chemotherapy. These results need to be confirmed by prospective studies. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-16
Author(s):  
Khe Hoang-Xuan ◽  
Roch Houot ◽  
Carole Soussain ◽  
Marie Blonski ◽  
Anna Schmitt ◽  
...  

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.


2017 ◽  
Vol 4 (1) ◽  
pp. 46-59 ◽  
Author(s):  
Agnieszka Korfel ◽  
Uwe Schlegel ◽  
Derek R. Johnson ◽  
Timothy J. Kaufmann ◽  
Caterina Giannini ◽  
...  

Abstract Primary CNS lymphoma (PCNSL) is a rare diffuse large B-cell lymphoma originating within the central nervous system. The overall incidence of PCNSL is rising, particularly in the elderly population. Immunosuppression is a strong risk factor, but most patients with this tumor are apparently immunocompetent. Diagnosis of PCNSL can be challenging. Non-invasive or minimally invasive tests such as ophthalmological evaluation and spinal fluid analysis may be useful, but the majority of patients require tumor biopsy for definitive diagnosis. Our knowledge concerning optimum treatment of PCNSL is fragmentary due to paucity of adequately sized trials. Most patients are now initially treated with high-dose-methotrexate-based chemotherapy alone, as the addition of whole-brain radiotherapy at standard doses has not been shown to increase survival and does increase the risk of neurological toxicity. Ongoing trials are addressing issues such as the roles of reduced-dose radiotherapy, the addition of the CD20 antibody rituximab to chemotherapy, high-dose chemotherapy followed by autologous stem cell transplantation, and maintenance therapy in the primary management of PCNSL.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1365-1365
Author(s):  
Agnieszka Korfel ◽  
Philipp Kiewe ◽  
Lars Fischer ◽  
Peter Mertus ◽  
Eckhard Thiel

Abstract Background This is a retrospective, long-term single-center analysis of immunocompetent patients with PCNSL treated at our institution. Methods All 72 consecutive patients diagnosed with PCNSL between January 1994 and February 2005 were scheduled to receive high-dose methotrexate (HDMTX; 1.5–4 g/m2) based chemotherapy. Results The median age of the patients was 62 years, the median Karnofsky performance status (KPS) was 70%. Twelve patients did not receive HDMTX based chemotherapy due to poor physical condition or renal insufficiency. Of 60 patients treated with HDMTX based chemotherapy, 9 were followed by whole brain irradiation (WBI). Of 54 patients evaluable for response 35 (65%) responded (52% CR and 13% PR), and 19 (35%) did not. At a median follow-up of 58.7 months, median progression-free survival (PFS) was 9 months, and median overall survival (OAS) was 41.4 months. Eight patients have survived 60 months or longer (median age 48, range 19–76; median KPS 80, range 40–100), 5 of whom relapsed after primary therapy at a median of 5 months (range, 3–39.7) after initial diagnosis. According to the Memorial Sloan-Kettering Cancer Center (MSKCC) prognosis score, patients could be divided into three groups with significantly different OAS: 52.9 months for patients younger than 50 years, 42.4 months for patients ≥50 years and with KPS ≥70, and 5.2 months for patients ≥50 years and KPS <70 (p=0.009; log-rank test). Eleven of 17 patients alive without cerebral lymphoma after 27–84 months tested exhibited clinical deficits attributable to late neurotoxicity. Conclusions This study providing long-term data shows that a relatively moderate HDMTX-based chemotherapy can result in prolonged survival and probably cure even in older and early relapsing patients. However, the probability of late neurotoxicity with prolonged survival is considerable. The comparison of our results to other retrospective studies underscore the importance of treating PCNSL patients preferably at experienced institutions. The MSKCC score proved useful to predict survival.


2017 ◽  
Vol 06 (04) ◽  
pp. 165-168 ◽  
Author(s):  
Rudresha H. A. ◽  
Tamojit Chaudhuri ◽  
Kuntegowdanahalli C Lakshmaiah ◽  
Govind Babu ◽  
K. N. Lokesh ◽  
...  

Abstract Background: Primary central nervous system lymphoma (PCNSL) is a rare form of aggressive extranodal non-Hodgkin's lymphoma which occurs in both immunocompromised and immunocompetent patients. It has an overall poor prognosis in spite of a multimodality treatment approach including chemotherapy and radiotherapy. This study attempts to further delineate the clinicopathological, immunohistochemical, and radiological profile of PCNSL at Kidwai Memorial Institute of Oncology, Karnataka, India. Materials and Methods: All the pathologically confirmed PCNSL cases between January 2010 and June 2016, at our center, were analyzed retrospectively. The influence of potential prognostic parameters on overall survival (OS) was investigated by log-rank test and Cox regression analysis. Results: Of the 26 PCNSL patients, 17 (65.3%) were males. Median age at diagnosis was 42.5 years. None of the patients had HIV or Epstein-Barr virus positivity and only four patients (15.4%) had B-symptoms. The most common location in the brain was cerebral hemispheres in 15 patients (57%) and 10 patients (38.5%) had multiple intracranial lesions. Histologically, all were diffuse large B-cell lymphomas, except one case of anaplastic large cell lymphoma. Immunohistochemically, 18 patients (69%) had MUM 1 positivity and 20 cases (77%) belonged to nongerminal center subtype. DeAngelis protocol was followed in 24 patients (92%), and among this cohort, Memorial Sloan Kettering Cancer Center Class 1 (n = 17) and Class 2 (n = 7) patients had a median OS of 25 months and 11 months, respectively. Conclusion: None of the potential prognostic factors had a statistically significant influence on OS in our patients. High-dose methotrexate combined with radiation is an effective therapeutic approach. However, further prospective studies with a large number of patients are needed to identify more effective primary chemotherapy regimens to further improve the treatment outcome.


2020 ◽  
Vol 4 (15) ◽  
pp. 3648-3658
Author(s):  
Andrés J. M. Ferreri ◽  
Teresa Calimeri ◽  
Maurilio Ponzoni ◽  
Flavio Curnis ◽  
Gian Marco Conte ◽  
...  

Abstract Rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) is the standard treatment of diffuse large B-cell lymphoma (DLBCL). Primary DLBCL of the central nervous system (CNS) (primary central nervous system lymphoma [PCNSL]) is an exception because of the low CNS bioavailability of related drugs. NGR–human tumor necrosis factor (NGR-hTNF) targets CD13+ vessels, enhances vascular permeability and CNS access of anticancer drugs, and provides the rationale for the treatment of PCNSL with R-CHOP. Herein, we report activity and safety of R-CHOP preceded by NGR-hTNF in patients with PCNSL relapsed/refractory to high-dose methotrexate-based chemotherapy enrolled in a phase 2 trial. Overall response rate (ORR) was the primary endpoint. A sample size of 28 patients was considered necessary to demonstrate improvement from 30% to 50% ORR. NGR-hTNF/R-CHOP would be declared active if ≥12 responses were recorded. Treatment was well tolerated; there were no cases of unexpected toxicities, dose reductions or interruptions. NGR-hTNF/R-CHOP was active, with confirmed tumor response in 21 patients (75%; 95% confidence interval, 59%-91%), which was complete in 11. Seventeen of the 21 patients with response to treatment received consolidation (ASCT, WBRT, and/or lenalidomide maintenance). At a median follow-up of 21 (range, 14-31) months, 5 patients remained relapse-free and 6 were alive. The activity of NGR-hTNF/R-CHOP is in line with the expression of CD13 in both pericytes and endothelial cells of tumor vessels. High plasma levels of chromogranin A, an NGR-hTNF inhibitor, were associated with proton pump inhibitor use and a lower remission rate, suggesting that these drugs should be avoided during TNF-based therapy. Further research on this innovative approach to CNS lymphomas is warranted. The trial was registered as EudraCT: 2014-001532-11.


2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuchen Wu ◽  
Xuefei Sun ◽  
Xueyan Bai ◽  
Jun Qian ◽  
Hong Zhu ◽  
...  

Abstract Background Secondary central nervous system lymphoma (SCNSL) is defined as lymphoma involvement within the central nervous system (CNS) that originated elsewhere, or a CNS relapse of systemic lymphoma. Prognosis of SCNSL is poor and the most appropriate treatment is still undetermined. Methods We conducted a retrospective study to assess the feasibility of an R-MIADD (rituximab, high-dose methotrexate, ifosfamide, cytarabine, liposomal formulation of doxorubicin, and dexamethasone) regimen for SCNSL patients. Results Nineteen patients with newly diagnosed CNS lesions were selected, with a median age of 58 (range 20 to 72) years. Out of 19 patients, 11 (57.9%) achieved complete remission (CR) and 2 (10.5%) achieved partial remission (PR); the overall response rate was 68.4%. The median progression-free survival after CNS involvement was 28.0 months (95% confidence interval 11.0–44.9), and the median overall survival after CNS involvement was 34.5 months. Treatment-related death occurred in one patient (5.3%). Conclusions These single-centered data underscore the feasibility of an R-MIADD regimen as the induction therapy of SCNSL, further investigation is warranted.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junyao Yu ◽  
Huaping Du ◽  
Xueshi Ye ◽  
Lifei Zhang ◽  
Haowen Xiao

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.


2019 ◽  
Vol 7 ◽  
pp. 232470961989354
Author(s):  
Gliceida M. Galarza Fortuna ◽  
Kathrin Dvir ◽  
Christopher Febres-Aldana ◽  
Michael Schwartz ◽  
Ana Maria Medina

Primary central nervous system (CNS) lymphoma (PCNSL) is an uncommon extranodal non-Hodgkin lymphoma often presenting as a single brain lesion within the CNS. On histopathological evaluation of PCNSL a positive CD10, which is frequently observed in systemic diffuse large B-cell lymphoma, is present in approximately 10% of PCNSL. We describe a case of CD10-positive PCNSL presenting with multiple posterior fossa enhancing lesions in an immunocompetent older woman with a history of breast cancer successfully treated by the RTOG 0227 protocol consisting of pre-irradiation chemotherapy with high-dose methotrexate, rituximab, and temozolomide for 6 cycles, followed by low-dose whole-brain radiation and post-irradiation temozolomide.


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