scholarly journals ML-02 Chemotherapy for patients with relapsed or refractory primary CNS lymphoma

2020 ◽  
Vol 2 (Supplement_3) ◽  
pp. ii15-ii15
Author(s):  
Motoo Nagane ◽  
Nobuyoshi Sasaki ◽  
Keiichi Kobayashi ◽  
Kuniaki Saito ◽  
Daisuke Shimada ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Standard Of Care ◽  
Median Number ◽  
Salvage Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Brain Radiotherapy ◽  
First Relapse ◽  
Btk Inhibitor

Abstract BACKGROUNDS: Standard of care for patients with primary CNS lymphoma (PCNSL) has been high-dose methotrexate (HD-MTX)-based multiagent immunochemotherapy, particularly with R-MPV-A with or without whole-brain radiotherapy (WBRT), however, the optimal treatment for relapsed/refractory (r/r)PCNSL has not been established yet. Approval of a second-generation BTK inhibitor, tirabrutinib, for r/rPCNSL in Japan in March 2020, prompted us to evaluate retrospectively efficacy of R-MPV-A for r/rPCNSL to compare their activities. PATIENTS: Histologically proven PCNSL patients treated at relapse in our institution from April 2000 to November 2019 were analyzed. Outcomes were compared between those treated with RMPVA or other regimens. RESULTS: Among 148 PCNSL patients identified, 73 had at least one relapse, of whom 47 received salvage chemotherapy including 23 treated with RMPVA, 14 with HD-MTX monotherapy, and 11 with DeVIC (DEX, etoposide, ifosfamide, CDBCA). Median age/KPS were 69 yo (20–87)/ 80 (40–100), 27 patients had received prior WBRT. RMPVA was given at the first relapse in 11 patients, median number of RMPV cycles was 8 (1–4 cycles: 10; 8 cycles 13). CR/CRu were achieved in 19 (83%), response rate was 87%, while there were two PDs (9%). After median follow-up of 21.9 months, the median PFS after salvage RMPVA was 13.0 m (95%CI: 9.1–16.9), 1-year overall survival (OS) was 82%, median OS was 70.0 m (95%CI: 12.9–127.1), which were longer than those in 24 patients with salvage treatment other than RMPVA (mPFS 4.4 m, P=0.054; mOS 13.6 m, P=0.009). Median PFS and OS for HD-MTX monotherapy were 5.1m and 36.6 m, while those for DeVIC were 4.4 m and 9.1 m, respectively. Treatment was generally well-tolerated but there was one treatment-related death. CONCLUSIONS: Salvage RMPVA at relapses was active and associated with longer survival compared with other regimens, necessitating further development of salvage regimens incorporating tirabrutinib in the future studies.

scholarly journals CTNI-65. COMBINED RITUXIMAB, METHOTREXATE, PROCARBAZINE, VINCRISTINE, AND CYTARABINE (R-MPV-A) TREATMENT FOR PATIENTS WITH RELAPSED PRIMARY CNS LYMPHOMA

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii57-ii57
Author(s):  
Motoo Nagane ◽  
Nobuyoshi Sasaki ◽  
Keiichi Kobayashi ◽  
Kuniaki Saito ◽  
Daisuke Shimada ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Standard Of Care ◽  
Median Number ◽  
Salvage Chemotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Brain Radiotherapy ◽  
First Relapse ◽  
Btk Inhibitor

Abstract BACKGROUNDS Standard of care for patients with primary CNS lymphoma (PCNSL) has been high-dose methotrexate (HD-MTX)-based multiagent immunochemotherapy including an induction R-MPV with consolidation whole-brain radiotherapy (WBRT) and HD-cytarabine to achieve complete remission, however, the optimal treatment for relapsed/refractory (r/r) PCNSL has not been established yet, besides the recent approval of a BTK inhibitor, tirabrutinib, in Japan. We evaluated retrospectively efficacy of R-MPV-A for r/rPCNSL. PATIENTS Histologically proven PCNSL patients treated at relapse in our institution from April 2000 to November 2019 were analyzed. Outcomes were compared between those treated with RMPVA or other regimens. RESULTS Among 148 PCNSL patients identified, 73 had at least one relapse, of whom 47 received salvage chemotherapy including 23 treated with RMPVA either at the first relapse (11) or at the second or later relapse (12). Median age/KPS of this salvage RMPVA group were 71 (42–87)/80 (40–100). Nine patients were pretreated with the first-line RMPVA. HD-cytarabine was given to 13 patients. Median number of RMPV cycles was 8 (1–4 cycles: 10; 8 cycles 13). CR/CRu were achieved in 19 (83%), response rate was 87%, while there were two PDs (9%). After median follow-up of 21.9 months, the median PFS after salvage RMPVA was 13.0 m (95%CI: 9.1–16.9), 1-year overall survival (OS) was 82%, median OS was 70.0 m (95%CI: 12.9–127.1), which were longer than those in 24 patients with salvage treatment other than RMPVA (mPFS 4.4 m, P=0.054; mOS 13.6 m, P=0.009). Among patients with salvage RMPVA, HD-cytarabine was associated with better PFS (P=0.066), and complete responses were significantly correlated with longer OS. Treatment was generally well-tolerated but there was one treatment-related death. CONCLUSIONS Salvage RMPVA at relapses was active and associated with longer survival compared with other regimens, necessitating further development of salvage regimens incorporating tirabrutinib in the future studies.

scholarly journals NQPC-5 Does high-dose methotrexate-based chemotherapy for relapsed primary CNS lymphoma increase a risk of leukoencephalopathy with prior whole brain radiotherapy?

2021 ◽  
Vol 3 (Supplement_6) ◽  
pp. vi22-vi22
Author(s):  
Keiichi Kobayashi ◽  
Nobuyoshi Sasaki ◽  
Kuniaki Saito ◽  
Yuki Yamagishi ◽  
Naomi Hanayama ◽  
...  
Keyword(s):  
Performance Status ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Study Results

Abstract Backgrounds: Standard care for primary central nervous system lymphoma (PCNSL) comprises high-dose (HD) methotrexate (MTX) -based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). HD-MTX administration following WBRT has been suggested to increase a risk of leukoencephalopathy. However, given that there are no other agents with efficacy similar to or better than MTX, patients with relapsed PCNSL may often be treated with regimens containing HD-MTX if the initial MTX treatment achieved a long-term complete remission. Here, we retrospectively analyzed prevalence and an extent of white mater damages in association with prior WBRT in patients with relapsed PCNSL treated with HD-MTX based therapy. Patients & methods: Among 79 patients with relapsed/refractory PCNSL in a total of 162 patients with newly-diagnosed PCNSL treated in our institution from April, 2000 to February, 2021, 35 patients were identified with evaluable KPS, MMSE, and Fazekas scale data at both baseline and follow-up periods. Of the 35 patients, 22 were treated with chemotherapy at a relapse (10 with prior WBRT, while 12 without WBRT), and were included in this preliminary study. Results: In the WBRT group (male/female: 5/5), median age was 65 years (range, 45–73), initial median KPS was 70 (40–90), and median WBRT dose was 27 Gy (23.4–40). Median progression-free survival (mPFS) was 11.8 months, and median overall survival (mOS) was not reached. In the non-WBRT group (M/F 8/4), median age 75 (62–84), initial mKPS 80 (50–90), mPFS 16.2 m, and mOS not reached. Initial KPS and MMSE score tended to be worse in WBRT group, presumably due to enrichment of patients with poorer performance status and more comorbidities. A decline in the Fazekas score was not associated with MMSE deterioration.Conclusions: The preliminary analysis was not informative enough, and further extensive imaging analysis will be exploited.

scholarly journals Intensive Chemotherapy and Immunotherapy in Patients With Newly Diagnosed Primary CNS Lymphoma: CALGB 50202 (Alliance 50202)

2013 ◽  
Vol 31 (25) ◽  
pp. 3061-3068 ◽  
Author(s):  
James L. Rubenstein ◽  
Eric D. Hsi ◽  
Jeffrey L. Johnson ◽  
Sin-Ho Jung ◽  
Megan O. Nakashima ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Complete Response ◽  
Remission Induction ◽  
Cns Lymphoma ◽  
High Dose ◽  
Newly Diagnosed ◽  
Brain Radiotherapy ◽  
Myeloablative Chemotherapy

Purpose Concerns regarding neurocognitive toxicity of whole-brain radiotherapy (WBRT) have motivated development of alternative, dose-intensive chemotherapeutic strategies as consolidation in primary CNS lymphoma (PCNSL). We performed a multicenter study of high-dose consolidation, without WBRT, in PCNSL. Objectives were to determine: one, rate of complete response (CR) after remission induction therapy with methotrexate, temozolomide, and rituximab (MT-R); two, feasibility of a two-step approach using high-dose consolidation with etoposide plus cytarabine (EA); three, progression-free survival (PFS); and four, correlation between clinical and molecular prognostic factors and outcome. Patients and Methods Forty-four patients with newly diagnosed PCNSL were treated with induction MT-R, and patients who achieved CR received EA consolidation. We performed a prospective analysis of molecular prognostic biomarkers in PCNSL in the setting of a clinical trial. Results The rate of CR to MT-R was 66%. The overall 2-year PFS was 0.57, with median follow-up of 4.9 years. The 2-year time to progression was 0.59, and for patients who completed consolidation, it was 0.77. Patients age > 60 years did as well as younger patients, and the most significant clinical prognostic variable was treatment delay. High BCL6 expression correlated with shorter survival. Conclusion CALGB 50202 demonstrates for the first time to our knowledge that dose-intensive consolidation for PCNSL is feasible in the multicenter setting and yields rates of PFS and OS at least comparable to those of regimens involving WBRT. On the basis of these encouraging results, an intergroup study has been activated comparing EA consolidation with myeloablative chemotherapy in this randomized trial in PCNSL, in which neither arm involves WBRT.

Primary CNS Lymphoma Treated with HD-Methotrexate, HD-Busulfan/Thiotepa, Autologous Stem Cell Transplantation and Response-Adapted Whole-Brain Radiotherapy: Results of the Multicenter OSHO-53 Phase II - Study.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3342-3342 ◽  
Author(s):  
Michael Montemurro ◽  
Thomas Kiefer ◽  
Frank Schüler ◽  
Haifa-Katrin Al Ali ◽  
Hans-Heinrich Wolf ◽  
...  
Keyword(s):  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Cns Lymphoma ◽  
High Dose ◽  
Newly Diagnosed ◽  
Brain Radiotherapy ◽  
High Incidence

Abstract Purpose: This multicenter study investigated the efficacy and safety of high-dose methotrexate (HD-MTX) induction followed by high-dose busulfan/thiotepa with autologous stem-cell transplantation (HD-BuTT) and response-adapted whole-brain radiotherapy (WBRT) in patients with newly diagnosed primary CNS lymphoma. Patients and methods: 23 patients (median age 55 years) were treated in five centres. Patients received HD-MTX (4h-infusion; 8g/m2; >60y: 6g/m2) on d1 and d10 followed by leucapheresis. Then patients were stratified according to their results on neuroimaging: In case of at least a partial response, HD-BuTT consisting of 16mg busulfan / 10mg thiotepa per kg body weight followed by peripheral stem cell transplantation was given. Patients without response to induction or without complete response after high-dose therapy received WBRT (45Gy) as further treatment. Results: 16 patients received the planned treatment with HD-MTX followed by HD-BuTT. CR / PR rates for these patients were 19 % / 69 % after HD-MTX, 69 % / 13 % after HD-BuTT, 81 % / 6 % after HD-BuTT plus WBRT, respectively. Included the patients with early WBRT due to toxicity (n=2) and non-responders to HD-MTX induction (n=4) the overall response rate for all 23 patients was 83 % (intention-to-treat). Outcome was significantly influenced by the response to MTX-induction. There were three treatment-related deaths. Irradiated patients (n=9) had a high incidence of severe neurotoxicity leading to death in 3 patients. At a median follow-up of 15 months the median EFS and OS for all patients were 17 and 20 months, after HD-BuTT 27 months and “not reached”, respectively. Patients older than 60 years and younger patients have achieved similar outcomes. Conclusion: This study showed that HD-methotrexate induction followed by HD-BuTT is a feasible treatment option for newly diagnosed primary CNS lymphoma. Patients achieving CR after HD-BuTT show no signs of clinical neurotoxicity with median survival not reached yet. Time on treatment is 2–3 months only, but the induction treatment needs improvement to be more effective. WBRT in this study was associated with a high incidence of severe neurotoxicity and should therefore be avoided.

scholarly journals AT-59 * HIGH-DOSE MTX-BASED CHEMOTHERAPY FOR PRIMARY CNS LYMPHOMA: WITH OR WITHOUT WHOLE BRAIN RADIOTHERAPY? FINAL ANALYSIS OF G-PCNSL-SG-1

2014 ◽  
Vol 16 (suppl 5) ◽  
pp. v21-v22
Author(s):  
M. Weller ◽  
E. Thiel ◽  
P. Martus ◽  
R. Mohle ◽  
F. Griesinger ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Final Analysis ◽  
Cns Lymphoma ◽  
High Dose ◽  
Whole Brain ◽  
Brain Radiotherapy
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