Nordic MCL3 study: 90Y-ibritumomab-tiuxetan added to BEAM/C in non-CR patients before transplant in mantle cell lymphoma

• Published in: Blood Vol. 123; no. 19; pp. 2953 - 2959
• Main Authors: Kolstad, Arne, Laurell, Anna, Jerkeman, Mats, Grønbæk, Kirsten, Elonen, Erkki, Räty, Riikka, Pedersen, Lone Bredo, Loft, Annika, Bogsrud, Trond Velde, Kimby, Eva, Hansen, Per Boye, Fagerli, Unn-Merete, Nilsson-Ehle, Herman, Lauritzsen, Grete Fossum, Lehmann, Anne Kristine, Sundstrom, Christer, Karjalainen-Lindsberg, Marja-Liisa, Ralfkiaer, Elisabeth, Ehinger, Mats, Delabie, Jan, Bentzen, Hans, Schildt, Jukka, Kostova-Aherdan, Kamelia, Frederiksen, Henrik, Brown, Peter de Nully, Geisler, Christian H.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 08.05.2014; American Society of Hematology
• Subjects: Adult; Aged; Antibodies, Monoclonal - therapeutic use; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carmustine - administration & dosage; Clinical Trials and Observations; Combined Modality Therapy; Cyclophosphamide - administration & dosage; Cytarabine - administration & dosage; Disease-Free Survival; Etoposide - administration & dosage; Female; Humans; Kaplan-Meier Estimate; Lymphoma, Mantle-Cell - therapy; Male; Medicin och hälsovetenskap; Melphalan - administration & dosage; Middle Aged; Multivariate Analysis; Neoplasm, Residual - diagnosis; Prognosis; Radioimmunotherapy; Stem Cell Transplantation - methods; Time Factors; Transplantation, Autologous; Treatment Outcome
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2013-12-541953

The main objective of the MCL3 study was to improve outcome for patients not in complete remission (CR) before transplant by adding 90Y-ibritumomab-tiuxetan (Zevalin) to the high-dose regimen. One hundred sixty untreated, stage II-IV mantle cell lymphoma patients <66 years received rituximab (R)–maxi–CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) alternating with R-high-dose cytarabine (6 cycles total), followed by high-dose BEAM/C (bis-chloroethylnitrosourea, etoposide, cytarabine, and melphalan or cyclophosphamide) and autologous stem cell transplantation from 2005 to 2009. Zevalin (0.4 mCi/kg) was given to responders not in CR before transplant. Overall response rate pretransplant was 97%. The outcome did not differ from that of the historic control: the MCL2 trial with similar treatment except for Zevalin. Overall survival (OS), event-free survival (EFS), and progression-free survival (PFS) at 4 years were 78%, 62%, and 71%, respectively. For responding non-CR patients who received Zevalin, duration of response was shorter than for the CR group. Inferior PFS, EFS, and OS were predicted by positron emission tomography (PET) positivity pretransplant and detectable minimal residual disease (MRD) after transplant. In conclusion, positive PET and MRD were strong predictors of outcome. Intensification with Zevalin may be too late to improve the outcome of patients not in CR before transplant. This trial was registered at www.clinicaltrials.gov as #NCT00514475. •Z-BEAM/C did not improve outcome for patients in only PR or CRu before transplant.•Positive PET before transplant and MRD after transplant predicted inferior PFS and OS.