Primary CNS Lymphoma: Progress With Dose-Intensive Consolidation.
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ABSTRACT:
SUBMITTER: Rubenstein JL
PROVIDER: S-EPMC9649280 | biostudies-literature | 2022 Nov
REPOSITORIES: biostudies-literature
Publications
Primary CNS Lymphoma: Progress With Dose-Intensive Consolidation.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20220930 32
<i>The Oncology Grand Rounds series is designed to place original reports published in the</i> Journal <i>into clinical context. A case presentation is followed by a description of diagnostic and management challenges, a review of the relevant literature, and a summary of the authors' suggested management approaches. The goal of this series is to help readers better understand how to apply the results of key studies, including those published in</i> Journal of Clinical Oncology<i>, to patients s ...[more]
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Project description:The optimal consolidation strategy for primary central nervous system lymphoma (PCNSL) remains controversial. Preventing radio-induced neurotoxicity of consolidation treatment through reduced-dose whole-brain radiotherapy (rdWBRT) at a dose of 23.4 Gy is an interesting alternative to conventional WBRT in patients aged <60 years. From the LOC Network (Network for Oculo-cerebral Lymphomas) database, we retrospectively selected patients with PCNSL aged <60 years who showed complete (CR) or unconfirmed CR after high-dose methotrexate-based chemotherapy and had received consolidation rdWBRT as the first-line treatment. If available, prospective neuropsychological follow-ups were reported. Twenty-nine patients diagnosed between 2013 and 2018 met the study selection criteria. Nine (31%) patients experienced relapse during the follow-up, with a median time from radiotherapy to recurrence of 8.7 months (interquartile range, 4-11.5). Five of those patients received salvage treatment and consolidation with intensive chemotherapy and autologous stem cell transplantation. Progression-free survival rates were 89% (95% confidence interval [CI] 79%-100%), 72% (95% CI, 56%-88%), and 69% (95% CI, 52%-85%) at 1, 2, and 5 years, respectively. Overall survival rates were 100%, 89% (95% CI, 79%-100%), and 86% (95% CI, 74%-99%) at 1, 2, and 5 years, respectively, and were consistent with those observed for standard-dose WBRT (sdWBRT). No prognostic factor was identified. The results of the 36-month neuropsychological follow-up for a subset of patients appeared reassuring, with most patients exhibiting maintenance of or improvements in their baseline conditions. Our results, combined with phase 2 study results, support the use of rdWBRT instead of sdWBRT as a consolidation treatment in <60-year-old patients showing CR after induction treatment.
| S-EPMC9631661 | biostudies-literature
Project description:We evaluated a novel therapy for primary central nervous system lymphoma (PCNSL) with induction immunochemotherapy with high-dose methotrexate, temozolomide, and rituximab (MT-R) followed by intensive consolidation with infusional etoposide and high-dose cytarabine (EA). In addition, we evaluated the prognostic value of the minimum apparent diffusion coefficient (ADC(min)) derived from diffusion-weighted MRI (DW-MRI) in patients treated with this regimen.Thirty-one patients (median age, 61 years; median Karnofsky performance score, 60) received induction with methotrexate every 14 days for 8 planned cycles. Rituximab was administered the first 6 cycles and temozolomide administered on odd-numbered cycles. Patients with responsive or stable central nervous system (CNS) disease received EA consolidation. Pretreatment DW-MRI was used to calculate the ADC(min) of contrast-enhancing lesions.The complete response rate for MT-R induction was 52%. At a median follow-up of 79 months, the 2-year progression-free and overall survival were 45% and 58%, respectively. For patients receiving EA consolidation, the 2-year progression-free and overall survival were 78% and 93%, respectively. EA consolidation was also effective in an additional 3 patients who presented with synchronous CNS and systemic lymphoma. Tumor ADC(min) less than 384 × 10(-6) mm(2)/s was significantly associated with shorter progression-free and overall survival.MT-R induction was effective and well tolerated. MT-R followed by EA consolidation yielded progression-free and overall survival outcomes comparable to regimens with chemotherapy followed by whole-brain radiotherapy consolidation but without evidence of neurotoxicity. Tumor ADC(min) derived from DW-MRI provided better prognostic information for PCNSL patients treated with the MTR-EA regimen than established clinical risk scores.
| S-EPMC3288204 | biostudies-literature
Project description:AbstractConsolidation for primary central nervous system lymphoma (PCNSL) after induction chemoimmunotherapy include whole-brain radiotherapy (WBRT; ≤24 Gy reduced-dose [RD], >24 Gy standard-dose) and cytarabine, nonmyeloablative chemotherapy (NMC), or autologous hematopoietic cell transplantation (AHCT). Comparative outcomes are lacking. Outcomes from 1983-2020 were stratified by decade and Memorial Sloan Kettering Cancer Center recursive partitioning analysis (RPA) class. Clinicodemographic associations were analyzed by multinomial logistic regression. Progression-free survival (PFS) and overall survival (OS) were analyzed by proportional hazards. Of 559 patients, 385 (69%) were consolidated. Median follow-up and OS were 7.4 and 5.7 years, respectively. WBRT use declined (61% (1990s) vs 12% (2010s)), whereas AHCT (4% (1990s) vs 32% (2010s)) and NMC (27% (1990s) vs 52% (2010s)) rose. Compared with RPA 1, RPA 2 was more likely to receive NMC. Those with partial response to induction were less likely to receive AHCT (odds ratio, 0.36; P = .02). Among 351 with complete response to consolidation, only receipt of rituximab, methotrexate, procarbazine, and vincristine induction was associated with improved PFS (hazard ratio, 0.5; P = .006). Among RPA 1, median PFS and OS were not reached for AHCT or RD-WBRT, vs 2.5 and 13.0 years, respectively, after NMC. Among RPA class 3, median PFS and OS after RD-WBRT were 4.6 and 10 years, vs 1.7 and 4.4 years after NMC. No significant adjusted survival differences were seen across consolidation strategies. NMC is increasingly used in lieu of RD-WBRT despite a trend toward less favorable PFS. RD-WBRT can be considered in patients ineligible for AHCT.
| S-EPMC11696773 | biostudies-literature
Project description:Primary CNS lymphoma (PCNSL) is a rare form of extranodal non-Hodgkin lymphoma that is typically confined to the brain, eyes, and cerebrospinal fluid without evidence of systemic spread. The prognosis of patients with PCNSL has improved during the last decades with the introduction of high-dose methotrexate. However, despite recent progress, results after treatment are durable in half of patients, and therapy can be associated with late neurotoxicity. PCNSL is an uncommon tumor, and only four randomized trials and one phase III trial have been completed so far, all in the first-line setting. To our knowledge, no randomized trial has been conducted for recurrent/refractory disease, leaving many questions unanswered about optimal first-line and salvage treatments. This review will give an overview of the presentation, evaluation, and treatment of immunocompetent patients with PCNSL.
| S-EPMC5516483 | biostudies-literature
Project description:Primary diffuse large B-cell lymphoma (DLBCL) of the central nervous system is an aggressive malignancy that exhibits unique biological features and characteristic clinical behaviour, with overall long-term survival rates of around 20-40%. Clinical outcome has improved following the advent of chemoradiation protocols incorporating high-dose methotrexate in the mid-1980s, but disease relapse and adverse neurocognitive sequelae remain major clinical challenges. To address this, investigators have focused on improving drug therapy with novel cytotoxic combinations, monoclonal antibody therapy, and intensive chemotherapy consolidation approaches, in an attempt to improve disease control whilst reducing the requirement for whole-brain radiotherapy. Outcomes for patients that are older, immunocompromised, or have relapsed/refractory disease remain unsatisfactory and there is a paucity of clinical trial data to guide treatment of these groups. This review highlights recent advances in pathobiology, imaging, and clinical management of PCNSL and looks ahead to research priorities for this rare and challenging lymphoid malignancy.
| S-EPMC4180029 | biostudies-literature
Project description:Primary central nervous system lymphoma (PCNSL) is a rare and aggressive disease that originates from lymphocytes and develops in the central nervous system. There is no standard consolidation/maintenance therapy for PCNSL. While there exists a variety of options, the high chance of inferior outcomes for elderly patients and the risk of neurotoxicity requires exploration of alternative options for consolidation/maintenance therapy for PCNSL in the elderly population with CNS lymphoma. We treated one 77-year-old patient with single agent ibrutinib, a Bruton's tyrosine kinase inhibitor that crosses the blood-brain-barrier, as consolidation/maintenance therapy after induction therapy with high-dose methotrexate (HD-MTX) and rituximab plus temozolomide. This treatment resulted in good tolerance, further resolution of a small residue lymphoma, and sustained remission. The patient has completed one year of consolidation/maintenance therapy and is currently under clinical and imaging surveillance. She has survived 27 months without recurrence since diagnosis. This case shows the potential effectiveness of single agent ibrutinib as consolidation/maintenance therapy for PCNSL after induction therapy. More cases are needed to confirm the findings.
| S-EPMC9326764 | biostudies-literature
Project description:AimTo describe the long-term outcomes of patients with lymphoma in the CNS treated with rituximab, temozolomide and high-dose methotrexate without consolidation therapy.Patients & methodsA retrospective cohort study of 46 consecutive patients with primary CNS lymphoma (PCNSL, 27 patients) or secondary CNS involvement of diffuse large B-cell lymphoma (DLBCL, 19 patients) who were treated with rituximab on day 1 in combination with high-dose methotrexate (days 1 and 15) and temozolomide (days 1-5) in 28-day cycles without further consolidation.ResultsMedian follow-up was 21.2 months. Patients received a median of five cycles (range 1-15). Median overall survival (OS) was 26 months and median progression-free survival was 8.6 months. At 3 years, 37% of patients were alive and without evidence of disease. The patients with PCNSL had a significantly higher response rates (ORR 81 vs 47%; p = 0.015) and longer median OS (55.3 vs 4.8 months; p < 0.01) than those with secondary CNS DLBCL. Toxicities were mild and manageable.ConclusionThe rituximab, temozolomide and methotrexate regimen is an effective therapy for patients with PCNSL without the toxicities typically associated with consolidation therapy.
| S-EPMC6171986 | biostudies-literature
Project description:Primary central nervous system lymphoma (PCNSL) remains a disease with poor outcome and high recurrence rate. We retrospectively analyzed the clinical data of 243 immunocompetent patients with PCNSL in Beijing Tiantan Hospital. The median age of PCNSL patients was 57 years (range 10-95 years). For induction therapy, 94.7% of patients received high-dose methotrexate (HD-MTX) containing regimens, and 59.3% received rituximab, which increased over time. The overall response rate was 72.8%, with 58.8% achieving complete response. With a median follow-up of 27.0 months (95% confidence interval 23.6-30.4), the median progression-free survival (PFS) time was 14.0 months (95% CI 9.45-18.55), and the 2-year PFS rate was 33.2%. The median overall survival (OS) was not reached (NR), with an estimated overall survival rate at 4 years of 61.6%. Among 95 patients who completed sequential consolidation chemotherapy with either pemetrexed or etoposide plus cytarabine, the median PFS was 28 months (95% CI 17.11-38.89), and the estimated overall survival at 4 years was 78.7%. In conclusion, HD-MTX based induction chemotherapy with non-myeloablative sequential consolidation chemotherapy is an alternative feasible treatment option.
| S-EPMC8904393 | biostudies-literature
Project description:BackgroundPrimary central nervous system lymphoma (PCNSL) is a highly aggressive Non-Hodgkin lymphoma (NHL) with rising incidence over the past 30 years in immunocompetent patients. Although outcomes have improved, PCNSL is still associated with inferior prognosis compared to systemic NHL. Many questions regarding the optimal therapeutic approach remain unanswered.Methods/designThis is a randomized, open-label, international phase III trial with two parallel arms. We will recruit 250 patients with newly diagnosed PCNSL from approximately 35 centers within the networks of the German Cooperative PCNSL study group and the International Extranodal Lymphoma Study Group. All enrolled patients will undergo induction chemotherapy consisting of 4 cycles of rituximab 375 mg/m(2)/d (days 0 & 5), methotrexate 3.5 g/m(2) (d1), cytarabine 2 × 2 g/m(2)/d (d2-3), and thiotepa 30 mg/m(2) (d4) every 21 days. All patients will undergo stem-cell harvest after the second cycle. After 4 cycles of induction chemotherapy, patients achieving partial or complete response will be centrally randomized to 2 different consolidation treatments: (A) conventional-dose immuno chemotherapy with rituximab 375 mg/m(2) (d0), dexamethasone 40 mg/d (d1-3), etoposide 100 mg/m(2)/d (d1-3), ifosfamide 1500 mg/m(2)/d (d1-3) and carboplatin 300 mg/m(2) (d1) (R-DeVIC) or (B) high-dose chemotherapy with BCNU (or busulfan) and thiotepa followed by autologous stem cell transplantation (HCT-ASCT). The objective is to demonstrate superiority of HCT-ASCT compared to R-DeVIC with respect to progression-free survival (PFS, primary endpoint). Secondary endpoints include overall survival (OS), treatment response and treatment-related morbidities. Minimal follow-up after treatment completion is 24 months.DiscussionThe rationale for consolidation treatment in PCNSL is to eliminate residual lymphoma cells and to decrease the risk for relapse. This can be achieved by agents crossing the blood brain barrier either applied at conventional doses or at high doses requiring autologous stem cell support. HCT-ASCT has been shown to be feasible and highly effective in patients with newly-diagnosed PCNSL. However, it is unclear whether HCT-ASCT is really superior compared to conventional-dose chemotherapy after an intensified antimetabolites-based immunochemotherapy in patients with newly-diagnosed PCNSL. To answer this question, we designed this investigator initiated randomized phase III trial.Trial registrationGerman clinical trials registry DRKS00005503 registered 22 April 2014 and ClinicalTrials.gov NCT02531841 registered 24 August 2015.
| S-EPMC4839072 | biostudies-literature
Project description:PurposeA multicenter phase II study was conducted to assess the efficacy of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) followed by consolidation reduced-dose whole-brain radiotherapy (rdWBRT) and cytarabine in primary CNS lymphoma.Patients and methodsPatients received induction chemotherapy with R-MPV (five to seven cycles); those achieving a complete response (CR) received rdWBRT (23.4 Gy), and otherwise, standard WBRT was offered (45 Gy). Consolidation cytarabine was given after the radiotherapy. The primary end point was 2-year progression-free survival (PFS) in patients receiving rdWBRT. Exploratory end points included prospective neuropsychological evaluation, analysis of magnetic resonance imaging (MRI) white matter changes using the Fazekas scale, and evaluation of the apparent diffusion coefficient (ADC) as a prognostic factor.ResultsFifty-two patients were enrolled, with median age of 60 years (range, 30 to 79 years) and median Karnofsky performance score of 70 (range, 50 to 100). Thirty-one patients (60%) achieved a CR after R-MPV and received rdWBRT. The 2-year PFS for this group was 77%; median PFS was 7.7 years. Median overall survival (OS) was not reached (median follow-up for survivors, 5.9 years); 3-year OS was 87%. The overall (N = 52) median PFS was 3.3 years, and median OS was 6.6 years. Cognitive assessment showed improvement in executive function (P < .01) and verbal memory (P < .05) after chemotherapy, and follow-up scores remained relatively stable across the various domains (n = 12). All examined MRIs (n = 28) displayed a Fazekas score of ≤ 3, and no patient developed scores of 4 to 5; differences in ADC values did not predict response (P = .15), PFS (P = .27), or OS (P = .33).ConclusionR-MPV combined with consolidation rdWBRT and cytarabine is associated with high response rates, long-term disease control, and minimal neurotoxicity.
| S-EPMC5569679 | biostudies-literature