Randomized phase II study of rituximab, methotrexate (MTX), procarbazine, vincristine, and cytarabine (R-MPV-A) with and without low-dose whole-brain radiotherapy (LD-WBRT) for newly diagnosed primary CNS lymphoma (PCNSL).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 2501-2501
Author(s):  
Antonio Marcilio Padula Omuro ◽  
Lisa Marie DeAngelis ◽  
Theodore Karrison ◽  
Joe A Bovi ◽  
Marc Rosenblum ◽  
...  
Keyword(s):  
Phase Ii ◽  
Primary Endpoint ◽  
Neuropsychological Testing ◽  
Randomized Study ◽  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
The Elderly ◽  
Cns Lymphoma ◽  
Newly Diagnosed

2501 Background: MTX-based chemoradiotherapy is effective in PCNSL, but carries a risk of severe neurotoxicity (NT), especially in the elderly. In a phase II single arm study, R-MPV-A chemotherapy was combined with substantially reduced doses of radiotherapy (23.4 Gy), achieving prolonged progression free survival (PFS) and overall survival (OS) with acceptable NT. Because R-MPV-A had never been tested without radiotherapy, we conducted a randomized study to determine if the low doses of radiation played a role in the observed disease control, and to characterize NT as compared to chemotherapy alone. Methods: Patients were stratified by MSK RPA class and randomized to receive R-MPV-A with LD-WBRT (chemoRT arm) versus R-MPV-A alone (chemo arm). MTX dose was 3.5g/m2 infused over 2 hours. Filgrastim and pegfilgrastim support was given to all patients. LD-WBRT dose was 23.4 Gy (1.8 Gy X 13). The primary endpoint was intent-to-treat (ITT) PFS. A sample size of 89 would provide 80% power to detect a hazard ratio (HR) of 0.63, with one-sided alpha level of 0.15. Results: A total of 91 patients were randomized, of whom 4 were ineligible. Among eligible patients, 43 were enrolled in the chemoRT arm and 44 in the chemo arm. Median age was 66 (chemoRT) and 59 (chemo). Median KPS was 80 for both arms. Response rates following R-MPV were 81% (chemoRT) and 83% (chemo). In the chemoRT arm, 37 patients (86%) received LD-WBRT. After median follow-up of 55 months (m), the median ITT PFS was 25 m in the chemo arm and not reached in the chemoRT arm (HR 0.51; 95% CI [0.27, 0.95]; p = 0.015). The 2-year PFS was 54% (chemo) and 78% (chemoRT). Salvage radiotherapy has been given to 11 patients in the chemo arm. Median OS was not reached in either arm, with data still maturing. In both arms, most common grades 3 or 4 toxicities were anemia (27%), lymphopenia (41%), neutropenia (35%), thrombocytopenia (26%), ALT (23%) and AST (13%). One patient died from sepsis (chemo arm). As per investigators’ assessment, the rate of clinically defined moderate to severe NT was 11.4% (chemo) and 14% (chemoRT), p = 0.75. Conclusions: The study met the primary endpoint, demonstrating the addition of LD-WBRT to R-MPV-A improves PFS in newly diagnosed PCNSL. As per investigator’s assessment, NT rates were not statistically significantly increased, but further neuropsychological testing and neuroimaging analyses are ongoing to characterize cognitive decline and how it compares to other consolidation treatments. Clinical trial information: NCT01399372 .

Multicenter randomized phase II trial of methotrexate (MTX) and temozolomide (TMZ) versus MTX, procarbazine, vincristine, and cytarabine for primary CNS lymphoma (PCNSL) in the elderly: An Anocef and Goelams Intergroup study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 2032-2032 ◽  
Author(s):  
Antonio Marcilio Padula Omuro ◽  
Oliver L. Chinot ◽  
Luc Taillandier ◽  
Herve Ghesquieres ◽  
Carole Soussain ◽  
...  
Keyword(s):  
Neuropsychological Testing ◽  
Objective Response ◽  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
The Elderly ◽  
Abnormal Liver Function Test ◽  
Cns Lymphoma ◽  
Newly Diagnosed ◽  
Brain Radiotherapy ◽  
Pre Treatment

2032 Background: There is no standard chemotherapy defined in PCNSL. Elderly patients (pts) are not candidates for whole brain radiotherapy and therefore establishing an optimal MTX-based regimen is crucial. This prospective multicenter study conducted in 13 French institutions tested two promising MTX-based chemotherapy regimens in elderly pts with newly diagnosed PCNSL. Methods: Pts with histologically confirmed newly diagnosed PCNSL with age ≥60 and KPS ≥40 were stratified by institution and KPS, then randomized to receive three 28-day cycles of MTX (3.5 g/m2 D1 and D15) and TMZ (100-150mg/m2 D1-5 and 15-19) [MT arm] or 3 cycles of MTX (3.5 g/m2 D1 and D15), procarbazine 100mg/m2 (D1-7), vincristine (1.4mg/m2 D1 and 15), followed by cytarabine consolidation (3g/m2/d X2d) [MPV-A arm]. Neither arm included radiotherapy; prophylactic G-CSF and standardized corticosteroids (methylprednisolone 60mg/d D1-5) were given to both arms. The primary endpoint was PFS (one-stage Fleming design; α= 5%; β=10%). Evaluations included neuropsychological testing and quality of life. Results: Accrual has been completed (7/2007- 3/2010), with 98 pts randomized and 95 analyzed (MT: 48 pts; MPV-A: 47). Pre-treatment characteristics were well balanced between the two arms (all pts: median age=72- range 60-85; median KPS= 70; range 40-100). In the MPV-A arm, the CR rate = 62% (vs 45% in MT arm [p=0.11]), objective response rate= 82% (vs 71%; p=0.23), median PFS= 9.5m (vs 6.1m; HR= 1.14- 95% CI [0.72 ; 1.81]; p=0.6) and median OS= 31m (vs 13.8m; HR= 1.4 - 95% CI [0.84 ; 2.34]; p=0.2). The incidence of grades 3-4 toxicities was 72% in the MPV-A vs 71% in the MT arm. Abnormal liver function test was the most common toxicity (MPV-A: 18 pts; MT: 21). Baseline cognitive impairment (MMSE >24 vs ≤24) predicted OS (p=0.04). Conclusions: This is the first randomized PCNSL study testing two different MTX-based combination regimens. In this elderly population, toxicities were frequent but similar in both arms, and all efficacy endpoints tended to favor the MPV-A arm. The MPV-A regimen is recommended for further development in PCNSL. Clinical trial information: NCT00503594.

scholarly journals ACTR-23. MAINTENANCE TREATMENT WITH IBRUTINIB FOLLOWING FIRST LINE METHOTREXATE-BASED IMMUNO-CHEMOTHERAPY IN ELDERLY PATIENTS WITH PRIMARY CNS LYMPHOMA (PCNSL). A PHASE 2 OPEN-LABEL STUDY

2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi17-vi18
Author(s):  
Osnat Bairey ◽  
Alexandra Benouaich-amiel ◽  
Shlomit Yust-Katz ◽  
Ronit Gurion ◽  
Tali Siegal
Keyword(s):  
Maintenance Treatment ◽  
Fungal Infections ◽  
Randomized Study ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Newly Diagnosed ◽  
First Line ◽  
Open Label

Abstract BACKGROUND Patients older than 60 years account for up to 70% of all PCNSL cases. Elderly PCNSL patients have median overall survival (OS) under 2 years and progression free survival (PFS) ranging between 6–16 months. Older patients have multiple comorbidities associated with low tolerability to high-dose (HD) chemotherapy. As maintenance treatment prolongs PFS and\or OS in several hematological malignancies we sought to investigate whether Ibrutinib maintenance may benefit elderly PCNSL patients. Ibrutinib was selected for maintenance since it has an impressive tolerability and activity in a range of systemic B-cell lymphomas. METHODS Single arm, open label, non-randomized study aiming to accrue 30 newly diagnosed PCNSL patients aged 60–85 years who received HD-methotrexate–based first line chemotherapy and have a documented response which is either partial (PR) or complete response (CR). The primary end-point is one and 2-year PFS and ibrutinib dose is 560mg/day. All patients undergo pre-maintenance neurocognitive evaluation which is repeated every 6 months. RESULTS Of the 16 patients screened for the study 2 were excluded due to relapse while on screening. 14 patients have been enrolled with a median age of 74 (61–80) years. The median interval between PCNSL diagnosis and start of ibrutinib maintenance is 7.6 (5.6–11.5) months. Currently, the median PFS is 22.5 (12–31.5) months. The adverse effects are largely grade 1/2 with rare grade 3/4 events. One patient discontinued treatment due to skin rash at 4.5 months. Two patients relapsed while on maintenance after 4 and 15 months of treatment. 3 patients with PR at enrolment improved to CR/CRu during maintenance. No invasive fungal infections have been observed. CONCLUSIONS Ibrutinib maintenance is feasible and well tolerated in newly diagnosed elderly PCNSL patients after first-line HD-MTX based treatment. The toxicity is mild to moderate. Enrollment is ongoing and updated outcomes will be presented at the meeting.

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.

scholarly journals P05.04 Phase 2 open-label study of maintenance treatment with ibrutinib following first line methotrexate-based immuno-chemotherapy in elderly patients with primary CNS lymphoma (PCNSL)

2019 ◽  
Vol 21 (Supplement_3) ◽  
pp. iii34-iii34
Author(s):  
O Bairey ◽  
A Amiel ◽  
S Yust-Katz ◽  
R Gurion ◽  
T Siegal
Keyword(s):  
Maintenance Treatment ◽  
Fungal Infections ◽  
Randomized Study ◽  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Cns Lymphoma ◽  
High Dose ◽  
Newly Diagnosed ◽  
First Line ◽  
Open Label

Abstract BACKGROUND Patients older than 60 years account for up to 70% of all PCNSL cases. Elderly PCNSL patients have median overall survival (OS) under 2 years and progression free survival (PFS) ranging between 6–16 months. Older patients have multiple comorbidities associated with low tolerability to high-dose (HD) chemotherapy. As maintenance treatment proved to prolong PFS and\or OS in several hematological malignancies we sought to investigate whether Ibrutinib maintenance may benefit elderly PCNSL patients. Ibrutinib was selected for maintenance since it has an impressive tolerability and activity in a range of systemic B-cell lymphomas. MATERIAL AND METHODS Single arm, open label, non-randomized study aiming to accrue 30 newly diagnosed PCNSL patients aged 60–85 years who received HD-methotrexate-based first line chemotherapy and have a documented response which is either partial (PR) or complete response (CR). The primary end-point is one and 2-year PFS and maintenance ibrutinib dose is 560mg/day. All patients undergo pre-maintenance neurocognitive evaluation which is repeated every 6 months. RESULTS Of the 14 patients screened for the study 2 were excluded due to relapse while on screening. 12 patients have been enrolled with a median age of 74 (61–80) years. The median interval between diagnosis of PCNSL and start of ibrutinib maintenance is 7.6 (5.6–11.5) months. Currently, the median PFS is 22.5 (12–31.5) months. The adverse effects are largely grade 1/2 with rare grade 3/4 events. One patient discontinued treatment due to skin rash at 4.5 months and she is still alive after 24 months. Two patients relapsed while on maintenance after 4 and 15 months of treatment. 3 patients with PR at enrolment improved to CR/CRu during maintenance. No invasive fungal infections have been observed. CONCLUSION Ibrutinib maintenance is feasible and well tolerated in newly diagnosed elderly PCNSL patients after first-line HD-Methotrexate based treatment. The toxicity is mild to moderate. Enrollment is ongoing and updated outcomes will be presented at the meeting.

scholarly journals High-dose methotrexate-based regimens and post-remission consolidation for treatment of newly diagnosed primary CNS lymphoma: meta-analysis of clinical trials

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Junyao Yu ◽  
Huaping Du ◽  
Xueshi Ye ◽  
Lifei Zhang ◽  
Haowen Xiao
Keyword(s):  
Meta Analysis ◽  
Primary Cns Lymphoma ◽  
Central Nervous System Lymphoma ◽  
Progression Free Survival ◽  
Complete Response ◽  
Cns Lymphoma ◽  
High Dose ◽  
High Dose Methotrexate ◽  
Newly Diagnosed ◽  
Dose Methotrexate

AbstractWith the exception of high-dose methotrexate (HD-MTX), there is currently no defined standard treatment for newly diagnosed primary central nervous system lymphoma (PCNSL). This review focused on first-line induction and consolidation treatment of PCNSL and aimed to determine the optimal combination of HD-MTX and the long-term beneficial consolidation methods. A comprehensive literature search of MEDLINE identified 1407 studies, among which 31 studies met the inclusion criteria. The meta-analysis was performed by using Stata SE version 15. Forest plots were generated to report combined outcomes like the complete response rate (CRR), overall survival, and progression-free survival. We also conducted univariate regression analyses of the baseline characteristics to identify the source of heterogeneity. Pooled analysis showed a CRR of 41% across all HD-MTX-based regimens, and three- and four-drug regimens had better CRRs than HD-MTX monotherapy. In all combinations based on HD-MTX, the HD-MTX + procarbazine + vincristine (MPV) regimen showed pooled CRRs of 63% and 58% with and without rituximab, respectively, followed by the rituximab + HD-MTX + temozolomide regimen, which showed a pooled CRR of 60%. Pooled PFS and OS showed that post-remission consolidation with autologous stem cell transplantation (ASCT) was associated with the best survival outcome, with a pooled 2-year OS of 80%, a 2-year PFS of 74%, a 5-year OS of 77%, and a 5-year PFS of 63%. Next, whole-brain radiation therapy (WBRT) + chemotherapy showed a pooled 2-year OS of 72%, 2-year PFS of 56%, 5-year OS of 55%, and 5-year PFS of 41%, with no detectable CR heterogeneity throughout the entire treatment process. In HD-MTX-based therapy of newly diagnosed PCNSL, MPV with or without rituximab can be chosen as the inductive regimen, and the rituximab + HD-MTX + temozolomide regimen is also a practical choice. Based on our study, high-dose chemotherapy supported by ASCT is an efficacious approach for consolidation. Consolidation with WBRT + chemotherapy can be another feasible approach.

scholarly journals Management and outcome of primary CNS lymphoma in the modern era

Neurology ◽  
2020 ◽  
Vol 94 (10) ◽  
pp. e1027-e1039 ◽  
Author(s):  
Caroline Houillier ◽  
Carole Soussain ◽  
Hervé Ghesquières ◽  
Pierre Soubeyran ◽  
Olivier Chinot ◽  
...  
Keyword(s):  
Karnofsky Performance Status ◽  
Performance Status ◽  
Real Life ◽  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Progression Free Survival ◽  
Population Based ◽  
Cns Lymphoma ◽  
High Dose ◽  
Population Based Study

ObjectiveReal-life studies on patients with primary CNS lymphoma (PCNSL) are scarce. Our objective was to analyze, in a nationwide population-based study, the current medical practice in the management of PCNSL.MethodsThe French oculo-cerebral lymphoma network (LOC) database prospectively records all newly diagnosed PCNSL cases from 32 French centers. Data of patients diagnosed between 2011 and 2016 were retrospectively analyzed.ResultsWe identified 1,002 immunocompetent patients (43% aged >70 years, median Karnofsky Performance Status [KPS] 60). First-line treatment was high-dose methotrexate-based chemotherapy in 92% of cases, with an increasing use of rituximab over time (66%). Patients <60 years of age received consolidation treatment in 77% of cases, consisting of whole-brain radiotherapy (WBRT) (54%) or high-dose chemotherapy with autologous stem cell transplantation (HCT-ASCT) (23%). Among patients >60 years of age, WBRT and HCT-ASCT consolidation were administered in only 9% and 2%, respectively. The complete response rate to initial chemotherapy was 50%. Median progression-free survival was 10.5 months. For relapse, second-line chemotherapy, HCT-ASCT, WBRT, and palliative care were offered to 55%, 17%, 10%, and 18% of patients, respectively. The median, 2-year, and 5-year overall survival was 25.3 months, 51%, and 38%, respectively (<60 years: not reached [NR], 70%, and 61%; >60 years: 15.4 months, 44%, and 28%). Age, KPS, sex, and response to induction CT were independent prognostic factors in multivariate analysis.ConclusionsOur study confirms the increasing proportion of elderly within the PCNSL population and shows comparable outcome in this population-based study with those reported by clinical trials, reflecting a notable application of recent PCNSL advances in treatment.

BCL6 Expression and Treatment Delay Correlate with Adverse Outcome in Newly Diagnosed Primary CNS Lymphoma: Final Report of CALGB 50202 (Alliance)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 301-301
Author(s):  
James L. Rubenstein ◽  
Eric D. Hsi ◽  
Jeffrey L. Johnson ◽  
Sin-Ho Jung ◽  
Barbara Grant ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Progression Free Survival ◽  
Treatment Delay ◽  
Cns Lymphoma ◽  
Newly Diagnosed ◽  
Event Free Survival ◽  
Free Survival ◽  
Brain Irradiation ◽  
Bcl6 Expression ◽  
Ecog Ps

Abstract Abstract 301 Background: While whole brain radiotherapy (WBRT) has long been considered the standard consolidative therapy in primary CNS lymphoma (PCNSL), concerns regarding irreversible neurocognitive effects of brain irradiation have prompted development of dose-intensive induction and consolidative chemotherapeutic approaches, with the aim to eliminate brain irradiation. We present the updated results of the first Phase II multicenter trial, conducted by a major cooperative group within the United States, to evaluate an intensive chemotherapy-alone strategy in newly diagnosed patients with PCNSL. Methods: Induction chemotherapy consisted of methotrexate (MTX), temozolomide, rituximab (MT-R) with HD-MTX (8 gm/m2) administered every 2 weeks × 8, weekly rituximab × 6 and temozolomide (150 mg/m2) starting day +7 and continued monthly × 5. Patients who achieved a CR received intensive consolidation cytarabine 2 gm/m2 BID on days 1–4 with etoposide 40 mg/kg over 96 h (EA). Assessment of BCL6 and MYC expression by lymphoma cells was performed by immunohistochemical analysis of diagnostic specimens and scored (10% increments) by a pathologist who was blinded to clinical outcome. Results: 44 newly diagnosed, immunocompetent patients with PCNSL were treated at 12 CALGB centers between 2005 and 2009. Patient characteristics were as follows: median age was 61 yr (range 12–76), median ECOG PS was 1, 58% were IELSG risk group 2–3. 98% of tumors were large B-cell lymphoma. 66% of patients exhibited CR to induction MT-R. With median overall follow-up of 5.3 years, 21 out of 46 patients exhibited disease progression and 17 have died. There was one treatment-related death (sepsis) during consolidation. There has been no evidence for significant treatment-related neurotoxicity. The median progression-free survival (PFS) is 4.0 years and estimated PFS rates with 95% confidence limits at 1, 2, 3 and 4 years are 0.66 (0.50, 0.76), 0.59 (0.43, 0.72), 0.52 (0.36, 0.64) and 0.47 (0.32, 0.61). The probability of 2-year PFS for patients who completed the entire regimen is 0.69 (0.47, 0.94). The estimated overall survival (OS) rate with 95% confidence limits at 4 years is 0.65 (0.49,0.77). Remarkably, event-free survival (EFS) was similar in patients older and younger than 60 (p< 0.47). While ECOG PS>1 and high IELSG score showed a trend toward inferior EFS, the most significant clinical prognostic variable was treatment delay: those patients who started remission induction therapy more than 30 days after diagnosis exhibited shorter EFS than patients who received MT-R within a month (2-sided p-value = 0.05). There was no relationship between treatment delay and IELSG prognostic score. While high MYC expression (>50% lymphoma nuclei) was detected in 54% of cases, MYC was not prognostic. By contrast, high BCL6 expression (≥30% of lymphoma nuclei) was detected in 59% of cases and correlated as a continuous variable with inferior progression-free survival, event-free survival and overall survival. The 2-sided p-values for these models were p=0.045, p=0.019 and p=0.045 (log-rank test). Conclusions: CALGB 50202 (Alliance) demonstrates that induction MT-R followed by EA consolidation is feasible in the multicenter setting and yields rates of PFS and OS in newly diagnosed PCNSL patients that are at least comparable to combined modality treatment involving reduced dose whole brain irradiation. The MT-R-EA regimen is well-tolerated in patients age >60 and has similar efficacy in this population as in younger patients. Based upon these encouraging results, a successor, intergroup, randomized phase II trial, CALGB 51101 (Alliance) has been activated that compares dose-intensive consolidation (EA) with myeloablative chemotherapy and autologous stem cell transplant in this first randomized trial in PCNSL in which neither arm involves WBRT. Our observations regarding the association of treatment delay with adverse prognosis suggest that prompt initiation of therapy for PCNSL patients may translate into improved outcomes. In this first prospective analysis of molecular biomarkers in PCNSL in the setting of a clinical trial, high BCL6 expression was found to correlate with inferior outcome. This observation raises the possibility that in future studies BCL6 could be used as a biomarker in risk-adapted therapy and supports the investigation of BCL6 antagonists in the treatment of this disease. Supported by LLS and by NCI CA13908301. Disclosures: No relevant conflicts of interest to declare.

Combined immunochemotherapy with reduced dose whole brain radiotherapy (WBRT) for newly diagnosed patients with primary CNS lymphoma (PCNSL)

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 1518-1518
Author(s):  
F. G. El Kamar ◽  
L. M. Deangelis ◽  
J. Yahalom ◽  
D. D. Correa ◽  
B. W. Grant ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Cns Lymphoma ◽  
Newly Diagnosed ◽  
Whole Brain ◽  
Reduced Dose ◽  
Brain Radiotherapy

Combined immunochemotherapy with reduced dose whole brain radiotherapy (WBRT) for newly diagnosed patients with primary CNS lymphoma (PCNSL)

2004 ◽  
Vol 22 (14_suppl) ◽  
pp. 1518-1518
Author(s):  
F. G. El Kamar ◽  
L. M. Deangelis ◽  
J. Yahalom ◽  
D. D. Correa ◽  
B. W. Grant ◽  
...  
Keyword(s):  
Primary Cns Lymphoma ◽  
Whole Brain Radiotherapy ◽  
Cns Lymphoma ◽  
Newly Diagnosed ◽  
Whole Brain ◽  
Reduced Dose ◽  
Brain Radiotherapy

Rituximab, methotrexate (MTX), procarbazine, and vincristine (R-MPV) followed by consolidation high-dose chemotherapy (HDC) and autologous stem-cell transplant (ASCT) for newly diagnosed primary CNS lymphoma (PCNSL).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2008-2008 ◽  
Author(s):  
Antonio Marcilio Padula Omuro ◽  
Denise Correa ◽  
Craig Moskowitz ◽  
Matthew J. Matasar ◽  
Lisa Marie DeAngelis ◽  
...  
Keyword(s):  
Induction Chemotherapy ◽  
Primary Endpoint ◽  
Primary Cns Lymphoma ◽  
Unknown Etiology ◽  
Cns Lymphoma ◽  
High Dose ◽  
Cell Transplant ◽  
Newly Diagnosed ◽  
Induction Regimen

2008 Background: In our previous study in newly diagnosed PCNSL, induction chemotherapy with MTX and cytarabine followed by consolidation HDC (carmustine, etoposide, cytarabine, melphalan [BEAM]) with ASCT without radiotherapy resulted in only 50% of pts transplanted, reflecting low efficacy of induction chemotherapy, and short intent-to-treat (ITT) median PFS (=6m). In this phase II trial, we sought to optimize this strategy by utilizing a more effective induction regimen (R-MPV) and a more aggressive HDC regimen (Soussain et al). Methods: Pts received 5-7 cycles of R-MPV (MTX: 3.5g/m2) and if a partial or complete response was achieved, HDC with thiothepa, cyclophosphamide and busulfan was given, followed by ASCT and no radiotherapy. The primary endpoint was ITT 1 year event-free survival (promising: 75%, non-promising: 50%; 90% power, significance=0.05). Follow-up included comprehensive neuropsychological evaluation. Results: Accrual has been completed (N=32 pts, median age 57 [range 23-67], median KPS=80). Following R-MPV, 17 pts achieved a CR, 13 pts a PR and two pts progressed. A total of 25 (78%) pts were transplanted; the reasons for not receiving transplant were progressive disease (N=2), poor performance status/ physician’s decision (N= 2), mobilization failure (N=1) and consent withdrawn (N= 2). One pt who withdrew consent relapsed and received HDCASCT for salvage. Two (8%) pts died from early complications of ASCT (Stevens-Johnson: one, sepsis: one) and one pt experienced a fatal late colitis of unknown etiology. In the ITT population, the median EFS and OS have not been reached after a median follow-up of 22 months. The 1 year EFS was 78% (95%CI 58-90) and the 2y OS was 76% (95% CI 54-89). No pt has developed delayed neurotoxicity. Conclusions: R-MPV induction regimen resulted in improved response rates, allowing 78% of pts to receive HDC-ASCT. Although more toxic, this regimen resulted in excellent disease control and survival in the ITT population, far exceeding the efficacy of our previous transplant study. The primary endpoint was met, warranting further investigation.

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