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 (>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 >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 >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 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 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.

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