scholarly journals ML-21 Tirabrutinib monotherapy for relapsed/refractory primary central nervous system lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii18-ii18
Author(s):  
Keiichi Kobayashi ◽  
Nobuyoshi Sasaki ◽  
Kuniaki Saito ◽  
Yuki Yamagishi ◽  
Yoshie Matsumoto ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Standard Of Care ◽  
Complete Response ◽  
Cell Receptor ◽  
Median Number ◽  
Grade 3

Abstract Backgrounds & purpose: Prognosis of patients with primary central nervous system lymphoma (PCNSL) remains poor despite multiagent immunochemotherapy, and standard of care for relapsed or refractory (r/r) PCNSL has not been established. Recent progresses on molecular genetics and biology of PCNSL have led to development of novel molecular targeted therapies, especially targeting Bruton’s tyrosine kinase (BTK), located in the B-cell receptor and Toll-like receptor signaling pathways. Tirabrutinb, a second generation BTK inhibitor, was approved for r/rPCNSL in March 2020 in Japan. Methods: Patients with r/rPCNSL treated with tirabrutinib since December 2017 were eligible for this retrospective study. Tirabrutinib was given orally at doses 320–480 mg/day daily until progression or unacceptable toxicity. Results: A total of 7 patients were enrolled (6 relapses, 1 refractory), 4 males, median age was 73 (range, 54–80 years), and median KPS was 70 (70–90). Three patients had received prior whole brain radiotherapy. Median number of prior therapies was 1 (1–2). Best overall response rate was 57.1%; 42.9% with a complete response (CR/CRu), 14.3% with a partial response (PR), while there were 3 PDs (42.9%). Four patients experienced PD and estimated median progression-free survival (mPFS) was 29.6 months. All patients were alive at the data cutoff with median follow up of 21.4 months (2–30.4). Common adverse events (AEs) include grade 4 neutropenia (n=1), grade 3 lymphopenia (n=3), and hepatic dysfunction (n=1). Toxic rash was observed in four patients (grade 3 in one, grade 2 in three) leading to discontinuation of tirabrutinib in two patients, while others continued on TIR with dose reduction and steroid use. The median time to rash presentation was 28 days (12–28). Conclusions: Tirabrutinib was well tolerated with frequent minor to moderate skin rash emerging within one month and active for r/rPCNSL. Long-term efficacy and safety profile need to be determined with a larger cohort.

scholarly journals RARE-51. RITUXIMAB, METHOTREXATE, BCNU, ETOPOSIDE, AND PREDNISONE (RMBVP) FOR THE TREATMENT OF RELAPSED/RECURRENT PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA: A RETROSPECTIVE SINGLE CENTER STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi232-vi232 ◽  
Author(s):  
Samantha Reiss ◽  
Prakirthi Yerram ◽  
Lisa Modelevsky ◽  
Christian Grommes
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Free Survival ◽  
Non Hodgkin Lymphoma ◽  
Single Center Study ◽  
Grade 3

Abstract BACKGROUND Primary Central Nervous System Lymphoma (PCNSL) is an aggressive rare non-Hodgkin lymphoma. Prognosis is particularly poor for relapsed/recurrent (R/R) patients with no established treatment modality. Methotrexate/BCNU/Teniposide/Prednisone with or without rituximab has efficacy in newly diagnosed PCNSL. Here, we report efficacy and toxicity of RMBVP for the treatment of R/R PCNSL. METHODS This retrospective study at MSKCC included PCNSLs treated with MBVP for R/R disease between 5/2009 and 5/2019. Methotrexate (3.5 g/m2; day 1 and 15), etoposide (100 mg/m2; day 2), BCNU (100 mg/m2; day 3), prednisone (60 mg/m2/day; day 1–5) and rituximab (500 mg/m2; day 0 and 14) were given in 28-day cycles. Granulocyte colony-stimulating factor support was given for 5 days in between doses of chemotherapy. RESULTS Thirty patients received MBVP; 27 (90%) received RMBVP with a median of 2 cycles given (0.5–5). Median age was 66 years (23–81); median KPS was 70 (30–90); 14 (46.7%) were women. Median prior lines of therapy were 2 (1–5); all received prior methotrexate. Median time from last treatment was 1 month (0–88.3; 21 (70%) < 12 months). Of twenty-nine evaluable patients for response, 23 (76.7%) had a response (9 complete response (CR) (30%), 5 CR-unconfirmed (16.7%), 8 partial response (26.7%), 1 stable disease (3%)). At a median follow up of 14.2 months, median progression free survival (PFS) was 15.6 months and median overall survival was not reached. Median PFS was poorer for patients with < 12 months since last chemotherapy, 10.1 vs 60.6 months. Rates of serious (grade 3 or 4) neutropenia, anemia, thrombocytopenia and transaminitis were 20%, 20%, 16.7%, and 16.7%, respectively. One patient experienced grade 3 nephrotoxicity. No treatment related mortalities occurred. CONCLUSIONS RMBVP is a tolerable treatment option for R/R PCNSL, particularly in those with recurrent disease.

scholarly journals INNV-21. EFFECTIVE REGIMEN OF HIGH-DOSE METHOTREXATE PLUS TEMOZOLOMIDE FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA: A SINGLE-CENTER RETROSPECTIVE STUDY

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii120-ii121
Author(s):  
Jun-ping Zhang ◽  
Jing-jing Ge ◽  
Cheng Li ◽  
Shao-pei Qi ◽  
Feng-jun Xue ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Retrospective Study ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Dose Methotrexate ◽  
Better Than

Abstract OBJECTIVE To evaluate the efficacy and safety of high-dose methotrexate combined with temozolomide in the treatment of newly diagnosed primary central nervous system lymphoma. METHODS A retrospective study was performed to analyze the clinical data of patients with primary central nervous system lymphoma treated with high-dose methotrexate plus temozolomide in the Department of Neuro-oncology, Capital Medical University, Sanbo Brain Hospital from May 2010 to December 2018. RESULTS A total of 41 patients were identified. Median age was 57 years (range, 27–76 years). The maximal extent of surgery was total resection in 6, partial resection in 8, and biopsy in 27 patients. Of the 35 patients with evaluable lesions, 32 achieved complete response (CR) and 3 achieved partial response. CR rate was 91.4%. The median follow-up time was 36.5 months (range, 4.9–115.4 months). After treatment, the median progression-free survival (PFS) was 45.1 months. PFS rate at 1, 2, 5 years were 85.4%, 70.1% and 43.8%, respectively. The OS rate at 1, 2, 5 years were 92.7%, 82.4% and 66.5%, respectively. The median PFS of patients younger than 65 years was better than that of patients ≥65 years (98.8 months vs 27.9 months, p=0.039). There was no association between efficacy and extent of resection (p=0.836). After disease progression, 6 of the 21 patients received radiotherapy. There was no statistical difference in OS between the patients with or without radiotherapy (36.9 months vs 28.4 months). The main severe adverse events were myelosuppression (36.6%) and elevated transaminase (34.1%). Three patients were discontinued due to drug-related toxicities. CONCLUSIONS High-dose methotrexate combined with temozolomide is effective in the treatment of primary central nervous system lymphoma, with a low incidence of severe adverse reactions. This efficacy may be better than the historical control of methotrexate alone or methotrexate plus rituximab.

Myeloablative versus non-myeloablative consolidative chemotherapy for newly diagnosed primary central nervous system lymphoma: Results of induction therapy in Alliance 51101.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 8042-8042
Author(s):  
Tracy Batchelor ◽  
Sharmila Giri ◽  
Amy S. Ruppert ◽  
Nancy L. Bartlett ◽  
Eric D. Hsi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Induction Therapy ◽  
Significant Proportion ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Whole Brain Radiation ◽  
Myeloablative Chemotherapy ◽  
Grade 3 ◽  
Dose Modifications

8042 Background: Optimal consolidative therapy for primary central nervous system lymphoma (PCNSL) is not defined. Avoidance of whole brain radiation may reduce risk of neurotoxicity. Non-radiation consolidative options include myeloablative chemotherapy followed by autologous stem cell transplantation (HDT/ASCT) or non-myeloablative chemotherapy. Methods: This is a randomized phase 2, National Clinical Trials Network study of induction methotrexate (MTX) (8 g/m2days 1, 15), temozolomide (TMZ) (150-200 mg/m2 D7-11), and rituximab (RTX) (C1 D3, 10, 17, 24 and C2 D3, 10) in four 28-day cycles followed by one cycle of cytarabine (ARA-C) (2 g/m2 BID, D1, 2) (MTRA). Following induction, patients (pts) received consolidation with thiotepa (5 mg/kg BID, D -5, -4) plus carmustine (400 mg/m2, day -6) and ASCT (Arm A) or one cycle of ARA-C (2 g/m2 BID, D1-4) plus infusional etoposide (40 mg/kg over 96h) (Arm B). The primary endpoint was median progression-free survival (PFS), designed to compare consolidation regimens. This report describes the results of the 5 cycles of induction therapy. Results: 113 pts (median age 61 years, range 33-75) were randomized (Arm A: 57, Arm B: 56) across 27 centers. 108 eligible pts who received induction therapy were evaluated. 36 pts (33.3%) did not proceed to consolidation, mainly due to disease progression (17), pt withdrawal (8), or adverse events including death (6). Grade 3 or 4 febrile neutropenia occurred in 12 pts (11.1%) during induction. Dose modifications of MTX were required in 75% of pts and 63.3% of cycles, mainly due to renal adjustments. Dose delays of MTX were required in 52.8% of pts and 22.2% of cycles. Overall response rate (CR, CRu, PR) at the end of induction was 65.7% (95% CI, 56%, 74.6%). Conclusions: While MTRA is feasible and active a significant proportion of pts did not receive consolidation, supporting the need to develop more effective induction strategies. Clinical trial information: NCT01511562 .

scholarly journals ML-02 MULTIAGENT IMMUNOCHEMOTHERAPY, R-MPV-A, FOR PATIENTS WITH SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii32-ii32
Author(s):  
Motoo Nagane ◽  
Keiichi Kobayashi ◽  
Kuniaki Saito ◽  
Daisuke Shimada ◽  
Yoshie Matsumoto ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Response Rate ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
University Hospital ◽  
High Dose ◽  
Serious Adverse Events

Abstract BACKGROUNDS Standard of care (SOC) for primary central nervous system lymphoma (PCNSL) has been induction therapy with high-dose methotrexate (MTX)-based multiagent immunochemotherapies followed by consolidation, and we have shown that one such regimen, R-MPV-A have superior efficacy over HD-MTX alone with whole brain radiotherapy (WBRT). While SOC for secondary CNS involvement of systemic diffuse large B-cell lymphoma (DLBCL)(SCNSL) has not been established. Here we report the outcome of R-MPV-A for patients with SCNSL. PATIENTS AND METHODS Fifteen patients with SCNSL treated with R-MPV-A from January 2014 to January 2019 in Kyorin University Hospital were eligible. Prior treatment for systemic DLBCL was mostly R-CHOP. Response and survival outcomes were evaluated. RESULTS Median age was 68.0 y (55–84), male/female 6/9, median KPS 70 (40–90), histopathological confirmation was achieved in 12 patients (80%; biopsy 11). RMPV (rituximab+MTX+procarbazine+vincristine) 3 cycles in 3, 4–7 cycles in 6, 8 cycles in 5. WBRT and cytarabine were delivered in 6 and 9 patients, respectively. R-MPV resulted in 6 CRs/CRus, 5 PRs, 1 SD, and 2 PDs (Response rate 73%). R-MPV-A including consolidation led to 9 CRs/CRus, 2 PRs, 1 SD, and 2 PDs (complete response rate 60%). With median F/U period of 11.2 m (0.1–51.5), 1y-PFS and 2y-PFS of R-MPV-A were 66.0% and 56.6%, 1y-OS and 2y-OS were 72.2% and 72.2%, respectively. Median PFS/OS were not reached. Consolidation cytarabine was associated with better outcome. Three deaths occurred during the treatment (20%; two during R-MPV with aged 70s, KPS 40 and 50; one presented MTX clearance delay). No other serious adverse events were observed. CONCLUSIONS These results suggest the certain efficacy of R-MPV-A for SCNSL. Being heavily pretreated frequently, precautions should be taken to identify high risk cases.

scholarly journals Consolidation Treatment for Primary Central Nervous System Lymphoma: Which Modality for Whom?

2020 ◽  
pp. 1-14
Author(s):  
Osnat Bairey ◽  
Liat Shargian-Alon ◽  
Tali Siegal
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Real Life ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
The Elderly ◽  
High Dose ◽  
Brain Radiotherapy ◽  
Randomized Studies

Primary central nervous system lymphoma is a rare aggressive disease that largely affects elderly patients and is associated with poor prognosis. The optimal treatment approach is not yet defined and it consists of induction and consolidation phases. The combination of high-dose (HD) methotrexate-based chemotherapy followed by whole-brain radiotherapy (WBRT) prolongs the median progression-free survival (PFS) and overall survival 2- to 3-fold as compared to WBRT alone but is associated with significant delayed neurotoxicity. Alternative strategies are being investigated in order to improve disease outcomes and spare patients the neurocognitive side effects. These include reduced-dose WBRT, non-myeloablative HD chemotherapy, or HD chemotherapy with autologous stem cell transplantation (HDC/ASCT). There are no randomized studies that compare all these consolidation regimens head to head but recently HDC/ASCT has been evaluated versus WBRT in prospective randomized studies. These studies proved that WBRT and HDC/ASCT yield similar 2-year PFS with preserved or improved cognitive function after HDC/ASCT. Yet, the proportion of patients treated with such intensive consolidation is low, both in real life and in specialized centers, leaving many unsettled issues. This review is appraising current dilemmas related to the choice of consolidating therapeutic modalities, their associated acute and delayed toxicity, and future prospects for alternative approaches in the elderly.

scholarly journals Salvage Therapy for Refractory Aids-Related Primary Central Nervous System Lymphoma

2012 ◽  
Vol 2012 ◽  
pp. 1-4
Author(s):  
Hugo Ferro ◽  
Eduardo Parino
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Salvage Therapy ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Neurological Status ◽  
Speech Disorders ◽  
High Dose

A 27-year-old male patient presented with speech disorders and multiple brain masses on MRI evaluation. He tested positive for HIV. A sterotactic biopsy diagnosed primary central nervous system lymphoma (diffuse large B-cell lymphoma). After two cycles of high-dose metotrexate (HD-MTX-)-based chemotherapy, the tumor progressed. He underwent whole brain radiotherapy achieving complete response. Six cycles of consolidating immunochemotherapy with rituximab-temozolomide were administered after radiation. Forty-three months after remission, he has not recurred and his neurological status is optimal. Younger HIV patients with refractory PCNSL and preserved immune function can face salvage therapy successfully achieving long term remissions with no remarkable neurotoxicity.

scholarly journals ML-08 Safety and efficacy of consolidation cytarabine for newly-diagnosed primary central nervous system lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii16-ii17
Author(s):  
Nobuyoshi Sasaki ◽  
Keiichi Kobayashi ◽  
Kuniaki Saito ◽  
Yuta Sasaki ◽  
Yuma Okamura ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Age Groups ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
High Dose ◽  
Consolidation Therapy ◽  
Safety And Efficacy ◽  
Dose Modification

Abstract Backgrounds: While consolidation therapies which incorporate whole brain radiotherapy (WBRT) and/ or chemotherapies such as high dose (HD)- cytarabine are commonly applied following induction chemotherapies in primary central nervous system lymphoma (PCNSL), the optimal treatment for consolidation therapy has not been established. We aimed to investigate the safety and efficacy of consolidation cytarabine with a dose modification policy in PCNSL. Patients and methods: PCNSL patients initially treated by R-MPV (rituximab, methotrexate, procarbazine and vincristine) and subsequently treated either by WBRT of 24Gy followed by cytarabine (WBRT-AraC group), or cytarabine alone (AraC group) were identified. WBRT was deferred in patients 71 years old or younger who had obtained a complete response (CR) after R-MPV. Cytarabine was dose-modified according to age groups (3 g/m2 in patients 70 years old or younger, 2 g/m2 in patients aged 71–75 years, 1 g/m2 in patients aged 76–80 years). Toxicity profiles, progression-free survival (PFS), overall survival (OS) were analyzed. Results: Twenty-five patients were identified (median age: 69 [range: 34–80], median KPS:70 [range: 40–90]), including 11 patients from the WBRT-AraC group, and 14 patients from the AraC group. Median PFS was unreached in the WBRT-AraC group, and 41.8 months in the AraC group. Median OS was unreached in both groups. The overall rate of grade 3/4 hematologic toxicities was high (92%), but mostly manageable without major complications. Fourteen patients received 3 g/m2, 4 patients received 2 g/m2, 7 patients received 1 g/m2 of cytarabine, and the rate of grade 4 leukopenia/ thrombocytopenia was 64%/57%, 25%/50%, and 29%/29%, respectively. Discussion: HD-cytarabine consolidation therapy with dose modification according to age groups for PCNSL was feasible and well-tolerated in patients 80 years of age or younger. The efficacy of HD-cytarabine was undetermined and further investigation is warranted.

scholarly journals ML-07 R-MPV-A THERAPY FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA IN THE ELDERLY: OUTCOME AND PROBLEM

2019 ◽  
Vol 1 (Supplement_2) ◽  
pp. ii33-ii33
Author(s):  
Hirotaka Fudaba ◽  
Yasutomo Momii ◽  
Kouhei Onishi ◽  
Daigo Asou ◽  
Minoru Fujiki
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Partial Response ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Complete Response ◽  
The Other ◽  
Brain Radiotherapy ◽  
Group A ◽  
Group B

Abstract PURPOSE R-MPV-A therapy has recently been reported to improve the outcomes of primary central nervous system lymphoma (PCNSL). Our patients have received R-MPV-A therapy since 2017 and elderly patients have only been treated with whole brain radiotherapy when they do not show a complete response after induction chemotherapy. We report the therapeutic outcomes and problems of elderly PCNSL patients treated with R-PMV-A. MATERIALS & METHODS Eight newly diagnosed PCNSL patients received R-MPV therapy from September 2017 to June 2019. We retrospectively reviewed the cycles of R-MPV therapy, radiotherapy, consolidation high-dose Ara-C (HD-Ara-C) therapy, and the G8 score (a geriatric assessment). RESULTS Patients were divided into three groups: Group A (71–75 years; n=2), Group B (76–80 years; n=4), and Group C (&gt;81 years; n=2). All Group A patients finished 5 cycles of R-MPV therapy, showed a complete response, and underwent consolidation HD-Ara-C therapy. Two Group B patients showed a complete response on R-MPV therapy. One of the other patients showed a partial response after 3 cycles of R-MPV therapy, and a &gt;3 kg reduction in body weight. The patient’s G8 score was 12 points. Whole brain radiotherapy (23.4 Gy) was administered followed by local radiotherapy (21.6 Gy). One patient showed a partial response after 7 cycles of R-MPV therapy and started radiotherapy. One Group C patient received radiotherapy after 3 cycles of R-MPV because of a new lesion. The other Group C patient showed acute renal damage after 3 cycles of R-MPV. CONCLUSION R-MPV-A therapy was relatively safe for our elderly PCNSL patients. Notably, patients &gt;76 years of age sometimes had severe adverse effect with increased R-MPV cycles. A promising therapeutic strategy based on age and geriatric assessment is needed.

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.

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