First-line therapy with temozolomide induces regression of primary CNS lymphoma

Abstract Introduction The optimal follow-up strategy for primary CNS lymphoma (PCNSL) patients in remission after first line therapy is not clear. The goal of this study is to determine the utility of planned brain surveillance imaging in the detection of relapse in a large cohort of PCNSL patients. Methods Patients were from consecutive PCNSL cases (N=209) included in Leon Berard Cancer Centre registry (Lyon, France), from 1987 to 2011 (date of diagnosis). Patients were all treated by chemotherapy, 92% of them by high-dose methotrexate containing chemotherapy followed by brain radiotherapy for 107 patients (51%). All patients were followed for relapse, retreatment and death. Patient clinical records were reviewed for details at relapse and relationship to planned follow-up visits and brain surveillance imaging. Results Among the 209 PCNSL patients, 28 (13%) presented toxic death, one patient died from another reason and 41 patients (20%) had a progressive disease during first-line therapy. The remaining 139 patients (66%) entered in post-treatment observation, 128 of them in complete remission (92%) and 11 in partial remission (8%). The median follow up was 36 months for the patients who entered in post-treatment observation. Among these 139 patients, 7 (5%) were lost of follow-up, 62 (45%) patients are still in remission and 70 (50%) relapsed. Among these 70 relapses, 15 (21%) were detected by planned brain surveillance imaging but 53 (76%) patients were symptomatic and presented earlier than a planned follow-up visit; two patients (3%) had no information at time of relapse. If we consider only patients in complete remission who entered in post-treatment observation, 13 (20%) relapses were detected by brain surveillance imaging and 50 (80%) patients presented symptoms between planned visits and imaging. Among the 7/11 patients considered in partial remission after initial treatment who relapsed, two (29%) relapses were detected by brain surveillance imaging and five (71%) by symptoms between planned visits and imaging. Among the 53 symptomatic patients at relapse, 41 (77%) presented a brain tumor relapse, six had an isolated leptomeningeal relapse, one a spinal cord localization and five an extra-cerebral relapse (three abdominal nodes, one soft-tissue mass, one testis). The most common symptoms at relapse were cognitive troubles, motor or sensitive deficits, epilepsy, and alteration of performance status. We did not observe any difference between asymptomatic relapse patterns before and after 2 years with 54% relapses before the two years of follow-up (brain imaging mainly every 4 months) and 46% relapses after 2 years of follow-up (brain imaging mainly every 6 months). Conclusions This study showed that PCNSL relapses frequently occurred outside of planned follow-up visits and were notably detected by symptoms between two brain surveillance imaging. Even during the two first years of follow-up with a closed brain imaging monitoring, planned surveillance imaging seemed not efficient. Disclosures: No relevant conflicts of interest to declare.

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Combination of Rituximab with Chemotherapy Improved Outcome of Newly Diagnosed Primary CNS Lymphoma: A Retrospective Study of 209 Unselected Patients Referred to a Single Institution

Blood ◽

10.1182/blood.v126.23.1544.1544 ◽

2015 ◽

Vol 126 (23) ◽

pp. 1544-1544

Author(s):

Herve Ghesquieres ◽

Celine Segura-Ferlay ◽

Gaelle Fossard ◽

Francois Ducray ◽

Violaine Safar ◽

...

Keyword(s):

Multivariate Analysis ◽

Protein Level ◽

Primary Cns Lymphoma ◽

Daily Practice ◽

Cns Lymphoma ◽

High Dose ◽

First Line ◽

First Line Therapy ◽

Meningeal Involvement ◽

Consolidation Radiotherapy

Abstract Introduction: Treatment of first-line therapy of primary CNS lymphoma (PCNSL) is based on high-dose methotrexate and cytarabine combination chemotherapy. Consolidation radiotherapy is mainly withdrawal for patients older than 60 years old regarding the excessive rate of neurological toxicity. Rituximab improved outcome of systemic diffuse large B-cell lymphoma but no data from randomized phase III trial is available to prove such outcome improvement for PCNSL. We introduced in daily practice intravenous rituximab in combination with chemotherapy for B-cell PCNSL in first-line therapy in 2004. The goal of this study is to determine whether such therapeutic modification improves PCNSL patient's outcome. Methods: Patients were from consecutive PCNSL cases (N=209) included in Leon Berard Cancer Centre registry (Lyon, France), from 1987 to 2011 (date of diagnosis). Median age of patients was 63 years (range, 26-87), 56% were male, 51% had a performance status (PS) >1, 63% had an involvement of deep structures of brain, 66% a high CSF protein level, 12% a meningeal involvement and 42% a high LDH level. Of the 171 available patients, 16% had 0-1, 60% had 2-3, and 24% had 4-5 adverse IELSG prognostic scores, respectively. Patients were all treated by chemotherapy, 92% and 63% of them by high-dose methotrexate and cytarabine containing chemotherapy, respectively followed by brain radiotherapy for 108 patients (58%). Intravenous rituximab was used in combination with chemotherapy in 61 patients (29%) between 2004 and 2011. Results: No difference in term of clinical characteristics (median age, PS, tumor site, CSF protein level, meningeal involvement, LDH level) was observed between patients treated with or without rituximab in combination with chemotherapy. With the median of 86.3 months (18.2-259), the median progression free survival (PFS) and overall survival (OS) for whole series were 17.3 months (95%CI, 10.7-25.9) and 35.6 months (95%CI, 22.7-50.0), respectively. The 3-year PFS were 55.5% (95%CI, 43-67) and 31.1% (95%CI, 24-39) for patients treated or not with rituximab, respectively (P=0.001). The 3-year OS were 73.6% (95%CI, 61-83) and 39.9% (95%CI, 32-48) for patients treated or not with rituximab, respectively (P<0.0001). A multivariate analysis was performed to test the impact of the addition of rituximab over clinical prognostic factors (age, PS, tumor site, CSF protein level, meningeal involvement, LDH level, IELSG score). Age>60 years (HR=1.74; 95%CI, 1.22-2.46; P=0.002), meningeal involvement (HR=2.33; 95%CI 1.42-3.85; P=0.0009) and used of rituximab (HR=0.50; 95%CI, 0.32-0.78; P=0.002) were identified as independent predictors of PFS. OS was significantly influenced by age>60 years (HR=1.94; 95%CI, 1.36-2.77; P=0.0002), PS (HR=1.76; 95%CI, 1.26-2.46; P=0.001), meningeal involvement (HR=2.17; 95%CI, 1.30-3.61; P=0.003) and used of rituximab (HR=0.39; 95%CI, 0.24-0.62; P=0.0001) in multivariate analysis. In a prognostic model integrating the IELSG score (0-1 vs. 2-3 vs. 4-5) (P=0.0002 for PFS and P<0.0001 for OS), used of rituximab was independently associated with the improvement of PFS (HR=0.60; 95%CI, 0.39-0.91; P=0.02) and OS (HR=0.44; 95%CI, 0.26-0.72; P=0.001). Disease free survival including patients who reached a complete response at the end of the first-line treatment was also improved by the used of rituximab (not reached versus 3.2 years, P=0.04). We also observed in this daily practice study, a reduction of the used of radiotherapy as first-line consolidation treatment (69% vs. 34%, P<0.001) before (1987-2003) and after (2004-2011) rituximab period. Conclusion: In this retrospective analysis, we showed that PCNSL patients treated with intravenous rituximab in combination with first-line chemotherapy had a better outcome. The frequency of consolidation radiotherapy was reduced for these patients treated at rituximab era. In multivariate analysis, CSF involvement was an independent adverse prognostic factor that inclines to improve meningeal explorations and propose new therapeutic options for CSF positive PCNSL patients. Disclosures No relevant conflicts of interest to declare.

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