Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis

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Leppä , S , Jorgensen , J , Tierens , A , Meriranta , L , Østlie , I , Brown , P D N , Fagerli , U-M , Larsen , T S , Mannisto , S , Munksgaard , L , Maisenholder , M , Vasala , K , Meyer , P , Jerkeman , M , Bjorkholm , M , Fluge , O , Jyrkklo , S , Liestol , K , Ralfkiaer , E , Spetalen , S , Beiske , K , Karjalainen-Lindsberg , M-L & Holte , H 2020 , ' Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis ' , Blood advances , vol. 4 , no. 9 , pp. 1906-1915 .

Title: Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis
Author: Leppä, Sirpa; Jorgensen, Judit; Tierens, Anne; Meriranta, Leo; Østlie, Ingunn; Brown, Peter de Nully; Fagerli, Unn-Merete; Larsen, Thomas Stauffer; Mannisto, Susanna; Munksgaard, Lars; Maisenholder, Martin; Vasala, Kaija; Meyer, Peter; Jerkeman, Mats; Bjorkholm, Magnus; Fluge, Oystein; Jyrkklo, Sirkku; Liestol, Knut; Ralfkiaer, Elisabeth; Spetalen, Signe; Beiske, Klaus; Karjalainen-Lindsberg, Marja-Liisa; Holte, Harald
Contributor organization: Department of Oncology
HUS Comprehensive Cancer Center
Research Programs Unit
Helsinki University Hospital Area
ATG - Applied Tumor Genomics
Faculty of Medicine
University of Helsinki
Department of Pathology
Date: 2020-05-12
Language: eng
Number of pages: 10
Belongs to series: Blood advances
ISSN: 2473-9529
Abstract: Survival of patients with high-risk diffuse large B-cell lymphoma (DLBCL) is suboptimal, and the risk of central nervous system (CNS) progression is relatively high. We conducted a phase 2 trial in 139 patients aged 18 to 64 years who had primary DLBCL with an age-adjusted International Prognostic Index (aaIPI) score of 2 to 3 or site-specific risk factors for CNS recurrence. The goal was to assess whether a dose-dense immunochemotherapy with early systemic CNS prophylaxis improves the outcome and reduces the incidence of CNS events. Treatment consisted of 2 courses of high-dose methotrexate in combination with biweekly rituximab (R), cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP-14), followed by 4 courses of R-CHOP-14 with etoposide (R-CHOEP) and 1 course of high-dose cytarabine with R. In addition, liposomal cytarabine was administered intrathecally at courses 1, 3, and 5. Coprimary endpoints were failure-free survival and CNS progression rates. Thirty-six (26%) patients experienced treatment failure. Progression occurred in 23 (16%) patients, including three (2.2%) CNS events. At 5 years of median follow-up, failure-free survival, overall survival, and CNS progression rates were 74%, 83%, and 2.3%, respectively. Treatment reduced the risk of progression compared with our previous trial, in which systemic CNS prophylaxis was given after 6 courses of biweekly R-CHOEP (hazard ratio, 0.49; 95% CI, 0.31-0.77; P=.002) and overcame the adverse impact of an aaIPI score of 3 on survival. In addition, outcome of the patients with BCL2/MYC double-hit lymphomas was comparable to the patients without the rearrangements. The results are encouraging, with a low toxic death rate, low number of CNS events, and favorable survival rates.
3122 Cancers
Peer reviewed: Yes
Rights: unspecified
Usage restriction: openAccess
Self-archived version: publishedVersion

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