Intensive Chemotherapy and Immunotherapy in Patients With Newly Diagnosed Primary CNS Lymphoma: CALGB 50202 (Alliance 50202)
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. 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. 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. 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.
- Research Article
4
- 10.1200/jco.2013.48.9138
- May 28, 2013
- Journal of Clinical Oncology
Flying Solo: Chemotherapy Without Radiation for Primary CNS Lymphoma
- Research Article
- 10.1182/blood-2025-1968
- Nov 3, 2025
- Blood
Improving outcomes with nivolumab consolidation among older patients (≥65) with previously untreated primary CNS lymphoma
- Research Article
- 10.1182/blood-2025-3703
- Nov 3, 2025
- Blood
Trial in progress: A phase 3, multi-regional, open-label, randomized study of tirabrutinib vs rituximab and temozolomide in participants with Relapsed/Refractory primary central nervous system lymphoma
- Research Article
1
- 10.1093/nop/npac052
- Jun 22, 2022
- Neuro-Oncology Practice
There is no consensus on the treatment of central nervous system (CNS) lymphoma refractory to first-line methotrexate-based chemotherapy. Whole brain radiotherapy (WBRT) is sometimes used but may result in unacceptable neurocognitive dysfunction. We examined the efficacy and toxicities of WBRT with or without concurrent temozolomide in CNS lymphoma treatment. This single-institution IRB-approved retrospective study included adults with CNS lymphoma who received WBRT, either consolidative low-dose WBRT alone or low-dose WBRT with a focal boost to residual disease and were previously treated with high-dose methotrexate. The relationships between the WBRT regimen, concurrent temozolomide, and clinical outcomes and toxicities were assessed using proportional hazards and logistic regression models. A total of 45 patients with a median age of 64 years (range 24-74) treated from 2004 to 2019 were included. In total, 20 patients received concurrent temozolomide. In the WBRT + Boost cohort (n = 32), concurrent temozolomide resulted in better 2-year overall survival (OS) and progression free survival (PFS) (73% OS and 66% PFS) compared to patients treated without concurrent temozolomide (44% OS and 24% PFS). On multivariate analysis, concurrent temozolomide was associated with significantly better PFS (HR 0.28, P = .02). There were no significant differences between the two radiation groups or between those treated with or without concurrent temozolomide, with respect to significant acute hematologic, non-hematologic, and long-term neurocognitive toxicities (P > .05). In this study, concurrent temozolomide with radiotherapy in CNS lymphoma was associated with better PFS and was well tolerated. Low-dose WBRT with a boost is a safe and reasonable treatment approach for focal refractory disease. Prospective research that includes rigorous neurocognitive assessments is now warranted.
- Abstract
4
- 10.1182/blood-2023-191123
- Nov 2, 2023
- Blood
Nivolumab and Ibrutinib for Treatment of Patients with Refractory or Relapsed Central Nervous System Lymphoma
- Research Article
5
- 10.1002/jha2.474
- Jun 2, 2022
- EJHaem
A multicenter, real-world analysis of primary central nervous system lymphoma in those with and without human immunodeficiency virus.
- Abstract
1
- 10.1182/blood.v120.21.301.301
- Nov 16, 2012
- Blood
BCL6 Expression and Treatment Delay Correlate with Adverse Outcome in Newly Diagnosed Primary CNS Lymphoma: Final Report of CALGB 50202 (Alliance)
- Abstract
2
- 10.1182/blood-2023-190961
- Nov 2, 2023
- Blood
Real-World Experience with RTOG 0227 Induction for First Line Therapy of Primary CNS Lymphoma (PCNSL)
- Abstract
2
- 10.1182/blood-2023-186488
- Nov 2, 2023
- Blood
Rituximab Ibrutinib Lenalidomide (R2I) Combination for Primary or Secondary Large B-Cell CNS Lymphoma: Last Resort or Bridge to Cellular Therapy?
- Abstract
- 10.1182/blood.v126.23.2701.2701
- Dec 3, 2015
- Blood
Long Term Outcomes of Rituximab, Temozolamide, and High-Dose Methotrexate for Lymphoma Involving the Central Nervous System
- Research Article
1
- 10.1200/jco.2024.42.16_suppl.e19046
- Jun 1, 2024
- Journal of Clinical Oncology
e19046 Background: Primary central nervous system lymphoma (PCNSL) lymphoma is a rare non-Hodgkin’s Lymphoma. Currently, there is no uniform consensus in the optimal management of PCNSL. In patients that can tolerate systemic therapy, induction therapy is typically done with a high-dose methotrexate-based regimen, due to evidence of better penetration of the blood brain barrier. One such regimens is high dose methotrexate combined with rituximab, procarbazine, and vincristine (R-MPV). Options for consolidation therapy include high-dose systemic therapy with stem cell rescue (ASCT), whole brain radio therapy (WBRT) and high-dose cytarabine (ara-c) with or without etoposide (EA). At our institution we utilize an R-MPV induction approach with some form of ara-c consolidation without etoposide. We aimed to execute a retrospective cohort study to analyze outcomes of this approach. Methods: All the patients diagnosed with PCNSL who received an induction regimen of R-MPV from 10/01/2020 to 06/01/2023 were included. Data was then gathered by chart review of the electronic medical record. Treatment outcomes were evaluated based on imaging with brain MRIs and PET scans. Central findings such as complete response (CR) rate, progression free survival (PFS) and overall survival (OS) were ascertained. Results: 10 charts were reviewed. 9 out of the 10 patients had a histological presentation consistent with diffuse large B-cell lymphoma; 1 patient had a diagnosis of B-cell lymphoma. In terms of demographics, the patients ages ranged from 54 to 83 years, with a median of 74 years. Complete response was achieved in 5 out of the 10 patients (CR rate of 50%), and no relapse was noted in any of these patients. 2 out of the 10 patients progressed on treatment, with 1 dying from progression of the disease. The median follow-up for patients who were still alive was 24 months. 2-year PFS was 80%, and 2-year OS was 90%. Median PFS and OS were not reached. Mean PFS and OS were 28 months and 30.5 months respectively. Conclusions: Based on our study results, the CR rate we observed for R-MPV appears consistent with existing literature on this regimen and other methotrexate-based induction regimens. Our results for R-MPV with ara-c consolidation provides similar outcomes to existing studies on treatment with different methotrexate-based induction and consolidation with ASCT, particularly the 80% PFS we observed. This percent PFS also appears similar to studies of consolidation with ara-c and EA, and superior to PFS with WBRT. Overall, these results are reassuring as in a specific set of older patients who might not be candidates for ASCT, our specific nonmyeloablative approach could be worthwhile. However, our study does have the limitation of being a single center retrospective perspective. [Table: see text]
- Abstract
- 10.1182/blood-2018-99-117225
- Nov 29, 2018
- Blood
Consolidative High Dose Chemotherapy and Autologous Stem Cell Transplant for Patients with Primary Central Nervous System (CNS) Lymphoma or Non-Hodgkin Lymphoma with CNS Involvement Using Thiotepa, Busulfan, and Cyclophosphamide Conditioning Regimen
- Abstract
- 10.1182/blood-2021-145133
- Nov 5, 2021
- Blood
A Multicenter, Real World Analysis of Primary Central Nervous System Lymphoma in Those with and without Human Immunodeficiency Virus
- Abstract
- 10.1182/blood-2024-198351
- Nov 5, 2024
- Blood
A Comparative Study of [18f]FDG PET and MRI for Evaluating Treatment Response in Primary CNS Lymphoma Patients Undergoing High-Dose Methotrexate Therapy
- Abstract
1
- 10.1182/blood-2023-179526
- Nov 2, 2023
- Blood
High-Dose Methotrexate Containing Induction Chemotherapy Followed By Nivolumab Consolidation in Older (≥ 65) Patients with Previously Untreated Primary CNS Lymphoma