G-PCNSL-SG-1 randomized phase III trial of high-dose methotrexate with or without whole brain radiotherapy for primary central nervous system lymphoma: Long-term follow-up.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 8527-8527 ◽  
Author(s):  
Agnieszka Korfel ◽  
Eckhard Thiel ◽  
Peter Martus ◽  
Robert Moehle ◽  
Frank Griesinger ◽  
...  
Keyword(s):  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Phase Iii ◽  
High Dose ◽  
Phase Iii Trial ◽  
Brain Radiotherapy ◽  
Dose Methotrexate ◽  
Long Term Follow Up

Long-Term Follow-Up of High-Dose Methotrexate-Based Therapy With and Without Whole Brain Irradiation for Newly Diagnosed Primary CNS Lymphoma

2006 ◽  
Vol 24 (28) ◽  
pp. 4570-4574 ◽  
Author(s):  
Igor T. Gavrilovic ◽  
Adília Hormigo ◽  
Joachim Yahalom ◽  
Lisa M. DeAngelis ◽  
Lauren E. Abrey
Keyword(s):  
Overall Survival ◽  
Whole Brain Radiotherapy ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Dose Methotrexate ◽  
Long Term Follow Up

Purpose We previously reported a series of patients treated with high-dose methotrexate (MTX) -based chemotherapy, with or without whole brain radiotherapy. The purpose of this report is to update the initial results and provide long-term data regarding overall survival, patterns of relapse, and the risk of treatment-related neurotoxicity. Patients and Methods Fifty-seven patients with an average age of 65 and median Karnofsky performance score of 70 were treated; all patients have been observed longitudinally with serial magnetic resonance imaging scans and neurologic examinations. Results The overall median survival was 51 months with a median follow-up of 115 months for surviving patients. Twenty-five patients relapsed or developed progressive disease; median progression-free survival was 129 months. Seventeen patients developed treatment-related neurotoxicity; all but one had received whole brain radiotherapy as a component of treatment. Seventy-four percent of patients younger than 60 years who received both MTX-based chemotherapy and whole brain radiotherapy were alive at last follow-up. Median survival for patients older than 60 years was 29 months regardless of whether or not they received whole brain radiotherapy. Conclusion Long-term follow-up of our initial cohort confirms the observation of excellent overall survival, particularly for those patients younger than age 60 at diagnosis. For older patients, it appears to be reasonable to defer whole brain radiotherapy in an effort to minimize treatment-related neurotoxicity.

Randomized phase III study of high-dose methotrexate and whole brain radiotherapy with or without concomitant and adjuvant temozolomide in patients with newly diagnosed primary central nervous system lymphoma: JCOG1114C.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2500-2500
Author(s):  
Kazuhiko Mishima ◽  
Ryo Nishikawa ◽  
Yoshitaka Narita ◽  
Junki Mizusawa ◽  
Minako Sumi ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Central Nervous System Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Hazard Ratio ◽  
Phase Iii ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Brain Radiotherapy ◽  
Dose Methotrexate

2500 Background: Temozolomide (TMZ) is an oral alkylating agent that penetrates the blood-brain barrier with moderate toxicity, and has shown anti-tumor activity in primary central nervous system lymphoma (PCNSL) in single arm studies. Our goal was to determine whether the addition of concomitant and adjuvant TMZ chemotherapy to standard treatment of high-dose methotrexate (HD-MTX) and whole brain radiotherapy (WBRT) for PCNSL improves survival in a randomized controlled trial. Methods: We did an open-label, randomized phase III trial at 30 hospitals in Japan enrolling immunocompetent patients (pts) aged 20-70 years with histologically confirmed newly diagnosed PCNSL. Pts enrolled at step 1 registration received HD-MTX (MTX; 3.5 g/m2 at day 1, 15, 29). Pts who received at least 1 cycle of HD-MTX were randomly assigned (1:1) at step 2 registration to receive WBRT (30 Gy) ± 10 Gy boost (control arm: A) or WBRT ± boost with concomitant TMZ (75 mg/m2 daily) and adjuvant TMZ (150-200 mg/m2 daily for 5 days every 28 days) for two years after initiation of HD-MTX or until tumor progression (experimental arm: B). Randomization was adjusted by institution, PS (0-1 / 2-3), age (≤60/≥61 years), presence or absence of intraparenchymal tumor after HD-MTX. The primary endpoint was overall survival (OS). The planned sample size was 130 pts in total, to provide an 80% power to detect a 0.52 hazard ratio (65% vs 80% in 2y-OS) for arm B to A and a one-sided alpha of 5%. Results: Between September 29, 2014 and October 15, 2018, 134 pts were enrolled, of whom 122 were randomly assigned and analyzed; 62 to arm A and 60 to arm B. At the planned interim analysis, the 2-y OS was 86.8% (95% CI: 72.5-94.0) in arm A and 71.4% (56.0-82.2) in arm B. The hazard ratio was 2.18 (95% CI: 0.95 to 4.98) with predictive probability for showing the superiority of arm B at the final analysis was calculated to be 1.3%. The study was terminated due to futility. The 2-y progression-free survival was 60.6% (43.6-73.8) in arm A and 49.9% (34.4-63.5) in arm B with a hazard ratio of 1.54 (0.88 to 2.70). The most common grade 3 and 4 toxicities were lymphopenia, observed in 7 (11.5%) pts during WBRT in arm A, 18 (30%) pts during WBRT + concomitant TMZ and 18 (37.5%) pts during adjuvant TMZ in arm B. Conclusions: This study failed to demonstrate the benefit of the addition of TMZ to WBRT and adjuvant TMZ in newly diagnosed PCNSL. Possible biomarkers including methylation status of the MGMT promoter in the tumors will be analyzed. Clinical trial information: jRCTs031180207 .

Long-term follow-up of autotransplant (AT)-supported high-dose melphalan (hdm) for multiple myeloma (MM): Update of Intergroup Francophone du Myelome (IFM), Southwest Oncology Group (SWOG), and Arkansas (ARK) Total Therapy (TT) trials

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 8519-8519
Author(s):  
B. Barlogie ◽  
M. Attal ◽  
J. Crowley ◽  
J. Harousseau
Keyword(s):  
Phase Iii ◽  
Long Term Results ◽  
High Dose ◽  
Long Term Follow Up ◽  
Phase Iii Trials ◽  
Trial Outcomes ◽  
Total Therapy ◽  
High Dose Melphalan

8519 Background: Clinical trial outcomes are usually published when statistical protocol objectives have been met, with short median follow-up not exceeding 5 years. Due to treatment innovations, MM survival beyond 10 years has become more common but formal long-term results are seldom reported. Methods: IFM, SWOG and ARK provide an update of their major trials. IFM-90: 1 AT v standard therapy (STD), IFM-94: 2 v 1 AT, IFM-9902: 2AT ± THAL, IFM-9904: 2AT for high-risk MM; SWOG-9321: 1 AT v STD; TT1: 2 AT with interferon, TT2: 2AT ± THAL, TT3: 2AT + THAL + bortezomib. Results: OS clustered in 3 groups with superior outcomes for TT3/TT2/IFM-99 v TT1 v IFM-94/ IFM-90/SWOG-9321 with 5/10/15-yr estimates of 70%/50%/TE v 57%/35%/20% v 43%/25%/15% (p<0.0001). EFS also clustered in 3 groups with superior outcomes for TT3 v TT2 v remainder with estimates of 71%/TE/TE v 50%/35%/TE v 27%/ 15%/10% (p<0.0001). Among phase III trials, added THAL in TT2 increased 10-yr OS/EFS from 40%/25% to 60%/40% (p=0.04/p=0.0005); 10-yr OS was 30% v 8% with 1 v 0 AT in IFM-90 (p=0.005), 31% v 21% with 2 AT v 1 AT in IFM-94 (p=0.08), and 20% for both arms of S9321. On multivariate analysis involving 2962 patients, OS was adversely affected by B2M >=3.5mg/L (p<0.001), LDH >=ULN (p<0.001), hemoglobin <10g/dL (p=0.001) and albumin <3.5g/dL (p=0.02). 2AT (65%) and THAL (21%) both contributed independently to superior OS (p<0.001, p=0.002); among individual trials, IFM-9902 (19%) and TT2/TT3 (33%) both improved OS significantly (both p<0.001). For each of the 3 major OS clusters, 228 patients could be matched on B2M, LDH, hemoglobin and albumin, with 10-yr OS/EFS estimates of 65%/30% for the TT3/TT2/IFM-9902 group significantly exceeding 30%/15% each for the other 2 groups (p=0.001/p=0.001). Conclusions: A 15-yr EFS plateau of 10% with older trials and superior 10-yr EFS/OS estimates of 50%/35% with recent studies emphasize that cure should be a realistic trial objective in contemporary MM therapy, requiring however very long-term follow-up beyond 15 years. [Table: see text]

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