Dataset Information

Treatment of newly diagnosed B-cell origin primary CNS lymphoma with systemic R-IDARAM chemotherapy and intrathecal immunochemotherapy.

ABSTRACT: Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin's lymphoma (NHL). The aim was to evaluate response rate, progression free survival (PFS), overall survival (OS), and toxicity in PCNSL after systemic R-IDARAM and intrathecal immunochemotherapy with deferred radiotherapy.The response rate was 94% with 17 (89%) complete responses and 1 (5%) partial responses. Follow-up time is from 5 to 63 months (median, 39 months). Median survival has not been reached. 3-year overall survival and progression-free survival rates were 84.2% (CI 72.6% to 99.8%) and 63.2% (CI 41.4% to 73.8%). Systemic toxicity was mainly hematologic. Neurocognitive and neuromotor deterioration as a result of treatment occurred in only one patient (5%).From September 2010 to June 2015, 19 consecutive patients with PCNSL (median age, 54 years) were enrolled into a pilot phase II study evaluating immunochemotherapy without radiotherapy. The patients were accrued to a chemotherapy regimen that incorporated rituximab, idarubicin, dexamethasone, cytarabine (Ara-c) and methotrexate (MTX) combined with intrathecal rituximab, MTX, dexamethasone and Ara-c.The results indicate that R-IDARAM regimen with intrathecal immunochemotherapy is generally well tolerated and produces a high complete response rate and survival rate.

SUBMITTER: Qian L

PROVIDER: S-EPMC5041943 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Treatment of newly diagnosed B-cell origin primary CNS lymphoma with systemic R-IDARAM chemotherapy and intrathecal immunochemotherapy.

Qian Liren L Zhou Chunhui C Shen Jianliang J Cen Jian J Yin Wenjie W

Oncotarget 20160501 18

<h4>Background</h4>Primary central nervous system lymphoma (PCNSL) is a rare subtype of non-Hodgkin's lymphoma (NHL). The aim was to evaluate response rate, progression free survival (PFS), overall survival (OS), and toxicity in PCNSL after systemic R-IDARAM and intrathecal immunochemotherapy with deferred radiotherapy.<h4>Results</h4>The response rate was 94% with 17 (89%) complete responses and 1 (5%) partial responses. Follow-up time is from 5 to 63 months (median, 39 months). Median survival ...[more]

PMID: 27029056

Similar Datasets

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.

Project description:BackgroundPrimary diffuse large B-cell lymphoma (DLBCL) of the central nervous system (PCNSL) is a rare disorder with an increasing incidence over the past decades. High-level evidence has been reported for the MATRix regimen (high-dose methotrexate (HD-MTX), high-dose AraC (HD-AraC), thiotepa and rituximab) followed by high-dose chemotherapy and autologous stem cell transplantation (HCT-ASCT) supporting this approach to be considered a standard therapy in newly diagnosed PCNSL patients ≤ 70 years. However, early treatment-related toxicities (predominantly infectious complications), occurring in up to 28% per MATRix cycle, diminish its therapeutic success. Furthermore, sensitivity to first-line treatment is an independent prognostic factor for improved overall survival (OS) in PCNSL. Thus, patients achieving early partial remission (PR) after 2 cycles of MATRix might be over-treated with 4 cycles, in the context of consolidation HCT-ASCT.MethodsThis is an open-label, multicentre, randomized phase III trial with two parallel arms. 326 immunocompetent patients with newly diagnosed PCNSL will be recruited from 37 German, 1 Austrian and 12 UK sites. Additional IELSG (International Extranodal Lymphoma Study Group) sites are planned. The objective is to demonstrate superiority of a de-escalated and optimised remission induction treatment strategy, followed by HCT-ASCT. Randomization (1:1) will be performed after completion of all screening procedures. Patients in Arm A (control treatment) will receive 4 cycles of MATRix. Patients in Arm B (experimental treatment) will receive a pre-phase (R/HD-MTX), followed by 2 cycles of MATRix. Patients in both arms achieving PR or better will proceed to HCT-ASCT (BCNU, thiotepa). The primary endpoint of the study is event-free-survival (EFS), defined as time from randomization to premature end of treatment due to any reason, lymphoma progression or death whichever occurs first. Secondary endpoints include OS, progression free survival (PFS), toxicity, neurocognitive impairment and quality of life. Minimal follow-up is 24 months.DiscussionCurrent treatment options for PCNSL in patients ≤ 70 years have improved remarkably over recent years. However, the potential efficacy benefits are offset by an increased incidence of short-term toxicities which can impact on treatment delivery and hence on survival outcomes. In patients ≤ 70 years with newly diagnosed PCNSL addressing the need to reduce treatment-related toxicity by de-escalating and optimising the induction phase of treatment, is a potentially attractive treatment strategy.Trial registrationGerman clinical trials registry DRKS00022768 registered June 10th, 2021.

Project description:IntroductionSoluble MHC class I-related chain A (sMICA) and B (sMICB) play a critical role tumor evolution and poor prognosis through an immune evasion mechanism. Thus, this study determines the interaction between sMICA/sMICB and the tumor immune environment in newly diagnosed diffuse large B-cell lymphoma (ND-DLBCL).MethodsWe analyzed sMICA/sMICB, cytokine in serum, and macrophage polarization analysis in tissue samples before the first chemotherapy administration. This research was performed to investigate the correlation between sMICA/sMICB expression and treatment outcomes as well as their influence on the immune system within ND-DLBCL.ResultsOf the 262 patients, 47.3% (n = 124) presented stage III or IV at diagnosis and 50.8% (n = 133) had a high International Prognostic Index (IPI ≥ 3). The patients with high (p = 0.034 and 0.004), elevated lactate dehydrogenase (p = 0.002 and 0.030), advanced stage (p = 0.003 and 0.012), and higher IPI risk (p = 0.009, and 0.032) correlated with the detection of sMICA or sMICB. The median progression-free survival (PFS) of patients with sMICA (p = 0.006) or sMICB (p =0.032) was inferior. Among the patients with advanced-stage or high IPI, those with sMICA or sMICB presented an inferior PFS and OS compared to those without. TNF-a, a pro-inflammatory cytokine, showed statistical significance with detected sMICA (p = 0.035) or sMICB (p = 0.044). Among anti-inflammatory cytokines, IL-1RA (P-value = 0.013) and IL-10 (p = 0.005) were associated with detecting sMICB, but not sMICA. In tissue samples, sMICA or sMICB detection did not correlate with the CD68/CD163 ratio.DiscussionConclusively, the identification of sMICA/sMICB presented unfavorable immunochemotherapy outcomes, and it was assumed that sMICA or sMICB and various cytokines interact, but the relationship with macrophage differentiation is unclear. Therefore, further research is needed to determine the relationship between sMICA/sMICB and tumor microenvironment in DLBCL.

Dataset Information

Treatment of newly diagnosed B-cell origin primary CNS lymphoma with systemic R-IDARAM chemotherapy and intrathecal immunochemotherapy.

Publications

Treatment of newly diagnosed B-cell origin primary CNS lymphoma with systemic R-IDARAM chemotherapy and intrathecal immunochemotherapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets