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Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma.

ABSTRACT: PURPOSE:Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited. METHODS:Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medical records. RESULTS:In total, 291 patients with SCNS were included. SCNS occurred as part of first relapse in 254 (87%) patients and 113 (39%) had concurrent systemic relapse. With a median post-SCNS follow-up of 48 months, the median post-SCNS OS was 3.9 months and 2-year OS rate was 20% (95% CI: 15-25). In multivariable analysis of 173 patients treated with curative/intensive therapy (such as high-dose methotrexate [HDMTX] or platinum-containing regimens), age ?60 years, performance status 0-1, absence of combined leptomeningeal and parenchymal involvement, and SCNS occurring after completion of first-line therapy were associated with superior outcomes. Patients ?60 years with performance status 0-1 and treated with HDMTX-based regimens for isolated parenchymal SCNS had a 2-year OS of 62% (95% CI: 36-80). In patients with isolated SCNS, the addition of rituximab to HDMTX-based regimens was associated with improved OS. Amongst patients with isolated SCNS in CR following intensive treatment, high-dose chemotherapy and autologous stem cell transplantation did not improve OS (P = 0.9). CONCLUSIONS:In this large international cohort of patients treated with first-line immunochemotherapy, outcomes following SCNS remain poor. However, a moderate proportion of patients with isolated SCNS who received intensive therapies achieved durable remissions.

SUBMITTER: El-Galaly TC

PROVIDER: S-EPMC5869165 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma.

El-Galaly Tarec Christoffer TC Cheah Chan Yoon CY Bendtsen Mette Dahl MD Nowakowski Grzegorz S GS Kansara Roopesh R Savage Kerry J KJ Connors Joseph M JM Sehn Laurie H LH Goldschmidt Neta N Shaulov Adir A Farooq Umar U Link Brian K BK Ferreri Andrés J M AJM Calimeri Teresa T Cecchetti Caterina C Dann Eldad J EJ Thompson Carrie A CA Inbar Tsofia T Maurer Matthew J MJ Gade Inger Lise IL Juul Maja Bech MB Hansen Jakob W JW Holmberg Staffan S Larsen Thomas S TS Cordua Sabrina S Mikhaeel N George NG Hutchings Martin M Seymour John F JF Clausen Michael Roost MR Smith Daniel D Opat Stephen S Gilbertson Michael M Thanarajasingam Gita G Villa Diego D

European journal of cancer (Oxford, England : 1990) 20180221

<h4>Purpose</h4>Secondary CNS involvement (SCNS) is a profoundly adverse complication of diffuse large B-cell lymphoma. Evidence from older series indicated a median overall survival (OS) < 6 months; however, data from the immunochemotherapy era are limited.<h4>Methods</h4>Patients diagnosed with SCNS during or after first-line immunochemotherapy were identified from databases and/or regional/national registries from three continents. Clinical information was retrospectively collected from medic ...[more]

PMID: 29477102

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Project description:BackgroundSecondary CNS lymphoma is a rare but potentially lethal event in patients with diffuse large B-cell lymphoma. We aimed to assess the activity and safety of an intensive, CNS-directed chemoimmunotherapy consolidated by autologous haematopoietic stem-cell transplantation (HSCT) in patients with secondary CNS lymphoma.MethodsThis international, single-arm, phase 2 trial was done in 24 hospitals in Italy, the UK, the Netherlands, and Switzerland. Adults (aged 18-70 years) with histologically diagnosed diffuse large B-cell lymphoma and CNS involvement at the time of primary diagnosis or at relapse and Eastern Cooperative Oncology Group Performance Status of 3 or less were enrolled and received three courses of MATRix (rituximab 375 mg/m2, intravenous infusion, day 0; methotrexate 3·5 g/m2, the first 0·5 g/m2 in 15 min followed by 3 g/m2 in a 3 h intravenous infusion, day 1; cytarabine 2 g/m2 every 12 h, in 1 h intravenous infusions, days 2 and 3; thiotepa 30 mg/m2, 30 min intravenous infusion, day 4) followed by three courses of RICE (rituximab 375 mg/m2, day 1; etoposide 100 mg/m2 per day in 500-1000 mL over a 60 min intravenous infusion, days 1, 2, and 3; ifosfamide 5 g/m2 in 1000 mL in a 24 h intravenous infusion with mesna support, day 2; carboplatin area under the curve of 5 in 500 mL in a 1 h intravenous infusion, day 2) and carmustine-thiotepa and autologous HSCT (carmustine 400 mg/m2 in 500 mL glucose 5% solution in a 1-2 h infusion, day -6; thiotepa 5 mg/kg in saline solution in a 2 h infusion every 12 h, days -5 and -4). The primary endpoint was progression-free survival at 1 year. Overall and complete response rates before autologous HSCT, duration of response, overall survival, and safety were the secondary endpoints. Analyses were in the modified intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT02329080. The trial ended after accrual completion; the database lock was Dec 31, 2019.FindingsBetween March 30, 2015, and Aug 3, 2018, 79 patients were enrolled. 75 patients were assessable. 319 (71%) of the 450 planned courses were delivered. At 1 year from enrolment the primary endpoint was met, 42 patients were progression free (progression-free survival 58%; 95% CI 55-61). 49 patients (65%; 95% CI 54-76) had an objective response after MATRix-RICE, 29 (39%) of whom had a complete response. 37 patients who responded had autologous HSCT. At the end of the programme, 46 patients (61%; 95% CI 51-71) had an objective response, with a median duration of objective response of 26 months (IQR 16-37). At a median follow-up of 29 months (IQR 20-40), 35 patients were progression-free and 33 were alive, with a 2-year overall survival of 46% (95% CI 39-53). Grade 3-4 toxicity was most commonly haematological: neutropenia in 46 (61%) of 75 patients, thrombocytopenia in 45 (60%), and anaemia in 26 (35%). 79 serious adverse events were recorded in 42 (56%) patients; four (5%) of those 79 were lethal due to sepsis caused by Gram-negative bacteria (treatment-related mortality 5%; 95% CI 0·07-9·93).InterpretationMATRix-RICE plus autologous HSCT was active in this population of patients with very poor prognosis, and had an acceptable toxicity profile.FundingStand Up To Cancer Campaign for Cancer Research UK, the Swiss Cancer Research foundation, and the Swiss Cancer League.

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Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma.

Publications

Treatment strategies, outcomes and prognostic factors in 291 patients with secondary CNS involvement by diffuse large B-cell lymphoma.

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