Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis
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Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis. / Leppä, Sirpa; Jørgensen, Judit; Tierens, Anne; Meriranta, Leo; Østlie, Ingunn; de Nully Brown, Peter; Fagerli, Unn-Merete; Larsen, Thomas Stauffer; Mannisto, Susanna; Munksgaard, Lars; Maisenhölder, Martin; Vasala, Kaija; Meyer, Peter; Jerkeman, Mats; Björkholm, Magnus; Fluge, Øystein; Jyrkkiö, Sirkku; Liestøl, Knut; Ralfkiaer, Elisabeth; Spetalen, Signe; Beiske, Klaus; Karjalainen-Lindsberg, Marja-Liisa; Holte, Harald.
In: Blood advances, Vol. 4, No. 9, 2020, p. 1906-1915.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Patients with high-risk DLBCL benefit from dose-dense immunochemotherapy combined with early systemic CNS prophylaxis
AU - Leppä, Sirpa
AU - Jørgensen, Judit
AU - Tierens, Anne
AU - Meriranta, Leo
AU - Østlie, Ingunn
AU - de Nully Brown, Peter
AU - Fagerli, Unn-Merete
AU - Larsen, Thomas Stauffer
AU - Mannisto, Susanna
AU - Munksgaard, Lars
AU - Maisenhölder, Martin
AU - Vasala, Kaija
AU - Meyer, Peter
AU - Jerkeman, Mats
AU - Björkholm, Magnus
AU - Fluge, Øystein
AU - Jyrkkiö, Sirkku
AU - Liestøl, Knut
AU - Ralfkiaer, Elisabeth
AU - Spetalen, Signe
AU - Beiske, Klaus
AU - Karjalainen-Lindsberg, Marja-Liisa
AU - Holte, Harald
N1 - © 2020 by The American Society of Hematology.
PY - 2020
Y1 - 2020
N2 - 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 www.clinicaltrials.gov as #NCT01325194.
AB - 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 www.clinicaltrials.gov as #NCT01325194.
U2 - 10.1182/bloodadvances.2020001518
DO - 10.1182/bloodadvances.2020001518
M3 - Journal article
C2 - 32380536
VL - 4
SP - 1906
EP - 1915
JO - Blood advances
JF - Blood advances
SN - 2473-9529
IS - 9
ER -
ID: 261535870