Treatment of Primary Central Nervous System Lymphoma: From Chemotherapy to Small Molecules

2018 ◽  
pp. 604-615 ◽  
Author(s):  
Joe S. Mendez ◽  
Christian Grommes
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Small Molecules ◽  
Checkpoint Inhibitors ◽  
Central Nervous System Lymphoma ◽  
Phase Iii ◽  
High Dose ◽  
First Line ◽  
The Past ◽  
Systemic Spread

Primary central nervous system lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid (CSF) without evidence of systemic spread. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting. The prognosis of patients with PCNSL has improved during the past few decades with the introduction of high-dose methotrexate (HD-MTX), which now serves as the backbone of all first-line treatment regimens. Despite recent progress, results after treatment are durable in half of patients, and therapy can be associated with late neurotoxicity. Novel insights into the pathophysiology of PCNSL have identified the B-cell receptor (BCR) pathway as a key mechanism in the pathogenesis of PCNSL. The use of novel agents targeting components of the BCR pathway, namely the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, and immunomodulatory drugs (IMIDs) like lenalidomide and pomalidomide, has so far been limited to patients who have recurrent/refractory PCNSL with promising high response rates. Within the past 5 years, there has been a peak in clinical trials investigating small molecules and novel reagents in the recurrent/refractory setting, including immune checkpoint inhibitors, IMIDs, and BTK and PI3K/AKT/mTOR inhibitors.

AUTOLOGOUS STEM CELL TRANSPLANTATION with INTRAVENOUS BUSULFAN, CYCLOPHOSPHAMIDE, and ETOPOSIDE as First-LINE TREATMENT of PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA in a SINGLE CENTER.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1219-1219
Author(s):  
Dok Hyun Yoon ◽  
Dae Ro Choi ◽  
Byeong Seok Sohn ◽  
Shin Kim ◽  
Dae Ho Lee ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Induction Chemotherapy ◽  
Conditioning Regimen ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Line Treatment ◽  
First Line ◽  
First Line Treatment

Abstract Abstract 1219 Poster Board I-241 Background High-dose chemotherapy followed by autologous stem cell transplantation (ASCT) has been evaluated in several trials and has shown feasibility as first-line treatment of primary central nervous system lymphoma (PCNSL). However, the best conditioning regimen is still to be identified and high-dose chemotherapy of busulfan, cyclophosphamide, and etoposide (BuCyE) has not been tried although the regimen was shown to be effective for leukemia and systemic non-Hodgkin's lymphoma. Methods Between May 2005 and November 2008, 12 consecutive patients of PCNSL with pathologic diagnosis of diffuse large-B cell lymphoma were treated with the intent of upfront ASCT at Asan Medical Center, Seoul, Korea. We retrospectively analyzed the results of these patients. The treatment included induction chemotherapy of high-dose methotrexate/cytarabine (Abrey et al., JCO 21:4151, 2003), followed by BuCyE chemotherapy consisting of iv busulfan (3.2mg/kg from day -7 to day -5), iv cyclophosphamide (50mg/kg from day -3 to day -2), and etoposide (200mg/m2 every 12 hours from day -5 to day -4), and ASCT. Whole brain radiotherapy (WBRT) was reserved for patients who failed to achieve complete response (CR) after ASCT. Results Median age was 50 years (range, 33-65) and 9 were male. The test of cerebrospinal fluid (CSF) cytology came out to be positive for 3 patients. Eight patients achieved CR and 4 gained partial response (PR) after induction chemotherapy. All 12 patients managed to complete ASCT. Following ASCT, additional 2 patients gained CR, resulting in total number of 10 patients (83.3%). Patients who failed to reach CR were further treated with WBRT and 2 more patients achieved CR. Median duration of first CR was 12.8 months (95% confidence interval [CI], 4.6-20.9) at a median follow-up of 23.8 months (range, 8.8-50.7). Relapse of disease occurred in 7 patients (58.3%) and 5 of them were given salvage treatment (Table 1). Two patients could regain CR and sustained remission for more than 2 years. Two patients had died of disease at the time of analysis. Median event-free survival (EFS) from the first day of induction chemotherapy was 15.0 months (95% CI, 8.3-21.8) and median overall survival (OS) was not reached. The 2-year OS probability was 78.8% and 2-year EFS was 25.7%. No patient experienced veno-occlusive disease or treatment-related mortality (TRM). Three patients among those who were treated with WBRT or intrathecal chemotherapy developed leukoencephalopathy. Conclusion BuCyE chemotherapy might be an option of conditioning regimen for ASCT considering high CR rate of 83.3% and favorable toxicity profile in the treatment of PCNSL. However, high relapse rate of 58.3% suggests that more optimization of induction and conditioning chemotherapy is still required. Disclosures No relevant conflicts of interest to declare.

scholarly journals Treatment of secondary central nervous system involvement in systemic aggressive B cell lymphoma using R-MIADD chemotherapy: a single-center study

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yuchen Wu ◽  
Xuefei Sun ◽  
Xueyan Bai ◽  
Jun Qian ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Involvement ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
B Cell Lymphoma ◽  
High Dose ◽  
Cns Involvement ◽  
The Central Nervous System ◽  
Secondary Central Nervous System

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.

scholarly journals RARE-29. PRIMARY CENTRAL NERVOUS SYSTEM NON-HODGKIN LYMPHOMA IN AN 11-YEAR-OLD BOY: A CASE REPORT

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii448-iii448
Author(s):  
Jorge Luis Ramírez-Melo ◽  
Regina M Navarro-Martin del Campo ◽  
Manuel D Martinez-Albarran ◽  
Fernando Sánchez-Zubieta ◽  
Ana L Orozco-Alvarado ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Hodgkin Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Complete Response ◽  
High Dose ◽  
Illustrative Case ◽  
Tumor Biopsy ◽  
Non Hodgkin Lymphoma ◽  
The Right

Abstract BACKGROUND Primary central nervous system lymphoma (PCNSL) are very rare in children. CLINICAL CASE: An 11-year-old male presented with a 2 months history with myoclonic movements in the upper right limb, and a sudden frontal headache, gait disturbance due to right hemiparesis and an ipsilateral convulsive episode. Upon admission he had critical condition, with hypertensive skull syndrome, Glasgow of 12, Karnofsky 40%, right hemiparesis, swallowing disorder, facial paralysis, and loss of photo motor reflex and unilateral amaurosis. A CT and MRI showed a huge tumor mass in the left tempo-parietal region, infiltrating the white matter and shifting the midline. A Tumor biopsy was done, and reported diffuse small cell non-Hodgkin lymphoma of high-grade, Burkitt type. Systemic lymphoma workup was negative. He received six cycles of chemotherapy based on high dose methotrexate, rituximab and triple intrathecal.After the second cycle an ophthalmologic evaluation was done, and found infiltration to the right retina, for which 6 cycles of intra vitreous chemotherapy with methotrexate were applied, he showed an excellent response, and recovered all his neurological functions except that right hemianopia persist. Control MRI showed partial response at 2nd cycle and complete response after the 4th cycle. No Radiation was performed. CONCLUSION This report highlights the fact that pediatric PCNSL may be effectively treated by a combination of HDMTX and rituximab-based chemoimmunotherapy without irradiation. Lack of awareness of this rare entity may lead to extense resections of brain, and potential permanent secuelae that were avoided in this illustrative case.

scholarly journals Primary Central Nervous System Lymphoma in Elderly Patients: Management and Perspectives

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3479
Author(s):  
Andrea Morales-Martinez ◽  
Fernando Lozano-Sanchez ◽  
Alberto Duran-Peña ◽  
Khe Hoang-Xuan ◽  
Caroline Houillier
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Elderly Patients ◽  
Treatment Strategies ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
Current Treatment ◽  
Cns Lymphoma ◽  
High Dose ◽  
Consolidation Phase

The management of elderly patients suffering from primary central nervous system (CNS) lymphoma, who represent a rapidly growing population, is challenging. Despite the advances made in PCNSL treatment, the prognosis in older patients remains unsatisfactory. The high risk of systemic and CNS toxicity induced by a high-dose chemotherapy regimen and radiation therapy, respectively, limits the use of consolidation phase treatments in elderly patients and contributes to the poor outcome of these patients. Here, we review the current treatment strategies and ongoing trials proposed for elderly PCNSL patients.

scholarly journals Patients with Primary Central Nervous System Lymphoma Not Eligible for Clinical Trials: Prognostic Factors, Treatment and Outcome

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2934
Author(s):  
Sabine Seidel ◽  
Michelle Margold ◽  
Thomas Kowalski ◽  
Alexander Baraniskin ◽  
Roland Schroers ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Clinical Trials ◽  
Nervous System ◽  
Prognostic Factors ◽  
Central Nervous System Lymphoma ◽  
Initial Response ◽  
Early Response ◽  
Multicenter Trial ◽  
High Dose ◽  
Therapeutic Trials

Patients with primary central nervous system lymphoma (PCNSL) not fulfilling inclusion criteria for clinical trials represent an underreported population. Thirty-four consecutive PCNSL patients seen at our center between 2005 and 2019 with exclusion criteria for therapeutic trials were analyzed (non-study patients) and compared with patients from the G-PCNSL-SG-1 (German PCNSL Study Group 1) study (study patients), the largest prospective multicenter trial on PCNSL, comprising 551 patients. Median follow up was 68 months (range 1–141) in non-study patients and 51 months (1–105) in study patients. Twenty-seven/34 (79.4%) non-study patients received high dose methotrexate (HDMTX), while seven/34 (20.6%) with a glomerular filtration rate (GFR) < 50 mL/min did not. Median overall survival (OS) was six months (95% confidence interval [CI] 0–21 months) in those 34 non-study patients. The 27 non-study patients treated with HDMTX were compared with 526/551 G-PCNSL-SG-1 study patients who had received HDMTX as well. Median OS was 20 months (95% CI 0–45)/21 months (95% CI 18–25) in 27 non-study/526 study patients (p = 0.766). Favorable prognostic factors in non-study patients were young age, application of HDMTX and early response on magnet resonance imaging (MRI). If HDMTX-based chemotherapy can be applied, long-term disease control is possible even in patients not qualifying for clinical trials. Initial response on early MRI might be useful for decision on treatment continuation.

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