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

Sirpa Leppä, Judit Jørgensen, Anne Tierens, Leo Meriranta, Ingunn Østlie, Peter de Nully Brown, Unn-Merete Fagerli, Thomas Stauffer Larsen, Susanna Mannisto, Lars Munksgaard, Martin Maisenhölder, Kaija Vasala, Peter Meyer, Mats Jerkeman, Magnus Björkholm, Øystein Fluge, Sirkku Jyrkkiö, Knut Liestøl, Elisabeth Ralfkiaer, Signe SpetalenKlaus Beiske, Marja-Liisa Karjalainen-Lindsberg, Harald Holte

Publikation: Bidrag til tidsskriftArtikelForskningpeer review


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. This trial was registered at as #NCT01325194.

Sider (fra-til)1906-1915
Antal sider10
TidsskriftBlood advances
Udgave nummer9
StatusUdgivet - 12 maj 2020

Bibliografisk note

© 2020 by The American Society of Hematology.


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