Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group.
Mantle cell lymphoma (MCL) is considered incurable. Intensive immunochemotherapy with stem cell support has not been tested in large, prospective series. In the 2nd Nordic MCL trial, we treated 160 consecutive, untreated patients younger than 66 years in a phase 2 protocol with dose-intensified induction immunochemotherapy with rituximab (R) + cyclophosphamide, vincristine, doxorubicin, prednisone (maxi-CHOP), alternating with R + high-dose cytarabine. Responders received high-dose chemotherapy with BEAM or BEAC (carmustine, etoposide, cytarabine, and melphalan/cyclophosphamide) with R-in vivo purged autologous stem cell support. Overall and complete response was achieved in 96% and 54%, respectively. The 6-year overall, event-free, and progression-free survival were 70%, 56%, and 66%, respectively, with no relapses occurring after 5 years. Multivariate analysis showed Ki-67 to be the sole independent predictor of event-free survival. The nonrelapse mortality was 5%. The majority of stem cell products and patients assessed with polymerase chain reaction (PCR) after transplantation were negative. Compared with our historical control, the Nordic MCL-1 trial, the event-free, overall, and progression-free survival, the duration of molecular remission, and the proportion of PCR-negative stem cell products were significantly increased (P < .001). Intensive immunochemotherapy with in vivo purged stem cell support can lead to long-term progression-free survival of MCL and perhaps cure. Registered at www.isrctn.org as #ISRCTN 87866680.
Geisler
Christian H
CH
Rigshospitalet, Copenhagen, Denmark. christian.geisler@rh.regionh.dk
Kolstad
Arne
A
Laurell
Anna
A
Andersen
Niels S
NS
Pedersen
Lone B
LB
Jerkeman
Mats
M
Eriksson
Mikael
M
Nordström
Marie
M
Kimby
Eva
E
Boesen
Anne Marie
AM
Kuittinen
Outi
O
Lauritzsen
Grete F
GF
Nilsson-Ehle
Herman
H
Ralfkiaer
Elisabeth
E
Akerman
Måns
M
Ehinger
Mats
M
Sundström
Christer
C
Langholm
Ruth
R
Delabie
Jan
J
Karjalainen-Lindsberg
Marja-Liisa
ML
Brown
Peter
P
Elonen
Erkki
E
D000328:Adult; D000368:Aged; D016465:Bone Marrow Purging; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007167:Immunotherapy; D019394:Ki-67 Antigen; D020522:Lymphoma, Mantle-Cell / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D013234:Stem Cells / Q000166:cytology*; D013997:Time Factors; D016896:Treatment Outcome
D019394:Ki-67 Antigen