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

Author:

Geisler Christian H.1,Kolstad Arne2,Laurell Anna3,Andersen Niels S.1,Pedersen Lone B.1,Jerkeman Mats4,Eriksson Mikael4,Nordström Marie5,Kimby Eva5,Boesen Anne Marie6,Kuittinen Outi7,Lauritzsen Grete F.2,Nilsson-Ehle Herman8,Ralfkiær Elisabeth1,Åkerman Måns4,Ehinger Mats4,Sundström Christer3,Langholm Ruth2,Delabie Jan2,Karjalainen-Lindsberg Marja-Liisa9,Brown Peter1,Elonen Erkki9,

Affiliation:

1. Rigshospitalet, Copenhagen, Denmark;

2. Norwegian Radium Hospital, Oslo, Norway;

3. Uppsala University Hospital, Uppsala, Sweden;

4. Lund University Hospital, Lund, Sweden;

5. Karolinska Institute, Stockholm, Sweden;

6. Aarhus University Hospital, Aarhus, Denmark;

7. Oulu University Hospital, Oulu, Finland;

8. Sahlgrenska Hospital, Gothenburg, Sweden; and

9. Helsinki University Central Hospital, Helsinki, Finland

Abstract

AbstractMantle 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.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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