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 .

Myeloablative versus non-myeloablative consolidative chemotherapy for newly diagnosed primary central nervous system lymphoma: Results of CALGB 51101 (Alliance).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 7506-7506
Author(s):  
Tracy Batchelor ◽  
Sharmila Giri ◽  
Amy S. Ruppert ◽  
Nancy L. Bartlett ◽  
Eric D. Hsi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Primary Endpoint ◽  
Performance Status ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Rank Test ◽  
Newly Diagnosed ◽  
Whole Brain Radiation ◽  
Myeloablative Chemotherapy

7506 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 with 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/m2 days 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). After 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). Pts were stratified on age and performance status and randomized 1:1 before induction. The primary endpoint was progression-free survival (PFS) from randomization. With 110 pts, there was 84% power to detect an improvement in PFS using a log-rank test (1-sided α= 10%), assuming a median PFS of 3 months for pts who progress during induction, and a median PFS of 2 years (yrs) for Arm B and 4.5 yrs for Arm A consolidation. This report includes the results for the primary endpoint analysis. Results: 113 pts (median age 61 yrs, range 33-75) were randomized (Arm A: 57, Arm B: 56) across 27 centers. 108 eligible pts who received induction therapy were included in the primary endpoint analysis (Arm A: 54, Arm B: 54). 72/108 pts started consolidation and 70/72 completed consolidation per protocol (Arm A: 36, Arm B: 34). With a median follow-up of 3.8 years, median PFS from randomization was 6 yrs (95% CI 3.9-not reached) in Arm A vs 2.4 yrs (95% CI 0.6-not reached) in Arm B (p = 0.02). However, more pts randomized to Arm B went off treatment before consolidation due to progression or death (28% vs 11%, p = 0.05). PFS landmarked at start of consolidation demonstrated a trend for improved PFS favoring Arm A (HR 0.58, 95% CI 0.25-1.36; p = 0.21). Median OS was not reached in either arm, and 3-yr estimates were 83% (95% CI 69-91; Arm A) vs 72% (95% CI 57-82; Arm B). Toxicities were similar between arms with no treatment-related mortality during consolidation. Conclusions: MTRA induction followed by myeloablative consolidation (Arm A) had improved PFS vs MTRA induction followed by non-myeloablative consolidation (Arm B), though more progressions or deaths leading to treatment discontinuation prior to consolidation in Arm B were noted. Both consolidation regimens were well-tolerated with encouraging PFS and OS in newly-diagnosed PCNSL. Support: U10CA180821, U10CA180882; https://acknowledgments.alliancefound.org . Clinical trial information: NCT01511562.

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 HOUT-16. A RETROSPECTIVE ANALYSIS OF SURVIVAL OUTCOMES BASED ON CONSOLIDATION REGIMENS IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi115-vi115
Author(s):  
Savannah Gelhard ◽  
Amiee Maxwell ◽  
Adam Cohen ◽  
Joe Mendez
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Induction Therapy ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Autologous Stem Cell Transplant ◽  
High Dose ◽  
Cell Transplant ◽  
Consolidation Therapy ◽  
Eligibility Criteria

Abstract BACKGROUND Currently, Primary Central Nervous System Lymphoma (PCNSL) is treated with induction therapy consisting of polychemotherapy followed by consolidation therapy. Besides the incorporation of high-dose methotrexate as the backbone of induction therapy, there is no accepted standard induction or consolidation regimen for patients with PCNSL in the US. In this study, we compared three consolidation techniques by analyzing overall survival (OS) and progression free survival (PFS) in patients treated for PCNSL. METHODS Patients treated for newly diagnosed PCNSL at Huntsman Cancer Institute after July 1, 2012 with induction followed by consolidation therapy were retrospectively reviewed. Patients who completed one of the following regimens were included: rituximab/methotrexate/vincristine/procarbazine (R-MVP), rituximab/methotrexate/temozolomide (R-MT), or rituximab/methotrexate (R-M) for induction followed by consolidation with etoposide/cytarabine (EA), high-dose cytarabine (HIDAC), or autologous stem cell transplant (ASCT). Patients were excluded if there was evidence of systemic lymphoma on PET/CT or if the patient received radiation as consolidation therapy. Survival was calculated from the date of diagnosis and last date of known survival. RESULTS Twenty-three patients met eligibility criteria and received the following four treatment regimens: R-MT+EA (12), R-MT+ASCT (4), R-M+ASCT (1), and R-MVP+HIDAC (6). The median age of diagnosis was 61. Patients receiving ASCT (5) had a trend towards a more favorable OS (p=0.0675) compared to the other two consolidation therapies with no recurrence or death in those patients treated with ASCT. When comparing non-transplanted patients, R-MVP-HIDAC had a trend towards better OS and PFS compared to R-MT-EA. CONCLUSION This small retrospective review provides evidence that ASCT may be a superior treatment consolidation strategy in patients with PCNSL compared to EA and HIDAC, and that R-MT-EA may be less successful in practice than in published trials. These findings suggest that consolidation with ASCT should be strongly considered in all patients with PCSNL despite which induction therapy was received.

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 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 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.

scholarly journals PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMAS

2015 ◽  
Vol 14 (2) ◽  
pp. 77-84
Author(s):  
Adriana Octaviana Dulamea ◽  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Treatment Strategies ◽  
Central Nervous System Lymphoma ◽  
B Cell Lymphoma ◽  
Diagnostic Methods ◽  
Hematopoietic Stem ◽  
Whole Brain Radiation ◽  
Author Review ◽  
Immunocompetent Patients

Primary central nervous system lymphoma (PCNSL) is an aggressive non-Hodgkin B-cell lymphoma with characteristic clinical behavior, biological features and poor prognosis despite complex treatment. PCNSL has a median survival of 17 to 45 months in immunocompetent patients, and only 20-30% of cases can be cured successfully. Clinical outcome has improved since the advances in combination chemotherapy protocols, addition of whole brain radiation therapy, encouraging responses of rituximab administration in refractory PCNSL and autologous hematopoietic stem-cell transplantation as consolidative therapy. The author review the recent data on pathogenesis, diagnostic methods and treatment strategies of PCNSL in immunocompetent patients.

scholarly journals Challenges in the Treatment of Newly Diagnosed and Recurrent Primary Central Nervous System Lymphoma

2020 ◽  
Vol 18 (11) ◽  
pp. 1571-1578
Author(s):  
Matthias Holdhoff ◽  
Maciej M. Mrugala ◽  
Christian Grommes ◽  
Thomas J. Kaley ◽  
Lode J. Swinnen ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
B Cell ◽  
Central Nervous System Lymphoma ◽  
High Dose Chemotherapy ◽  
High Dose ◽  
Newly Diagnosed ◽  
Phase Ii Trials ◽  
Whole Brain Radiation ◽  
The Central Nervous System

Primary central nervous system lymphomas (PCNSLs) are rare cancers of the central nervous system (CNS) and are predominantly diffuse large B-cell lymphomas of the activated B-cell (ABC) subtype. They typically present in the sixth and seventh decade of life, with the highest incidence among patients aged >75 years. Although many different regimens have demonstrated efficacy in newly diagnosed and relapsed or refractory PCNSL, there have been few randomized prospective trials, and most recommendations and treatment decisions are based on single-arm phase II trials or even retrospective studies. High-dose methotrexate (HD-MTX; 3–8 g/m2) is the backbone of preferred standard induction regimens. Various effective regimens with different toxicity profiles can be considered that combine other chemotherapies and/or rituximab with HD-MTX, but there is currently no consensus for a single preferred regimen. There is controversy about the role of various consolidation therapies for patients who respond to HD-MTX–based induction therapy. For patients with relapsed or refractory PCNSL who previously experienced response to HD-MTX, repeat treatment with HD-MTX–based therapy can be considered depending on the timing of recurrence. Other more novel and less toxic regimens have been developed that show efficacy in recurrent disease, including ibrutinib, or lenalidomide ± rituximab. There is uniform agreement to delay or avoid whole-brain radiation therapy due to concerns for significant neurotoxicity if a reasonable systemic treatment option exists. This article aims to provide a clinically practical approach to PCNSL, including special considerations for older patients and those with impaired renal function. The benefits and risks of HD-MTX or high-dose chemotherapy with autologous stem cell transplantation versus other, better tolerated strategies are also discussed. In all settings, the preferred treatment is always enrollment in a clinical trial if one is available.

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