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Long-term follow-up of 90Y-ibritumomab-tiuxetan (90YIT) in the conditioning of autologous hematopoietic transplantation for indolent and mantle cell lymphomas in a single French center

Bone Marrow Transplantation volume 51, pages 1140–1142 (2016)Cite this article

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High-dose therapy followed by autologous hematopoietic stem cell transplantation (ASCT) for refractory/relapsed indolent non-Hodgkin (iNHLs) and mantle cell lymphomas (MCLs) has shown significant improvement regarding PFS and overall survival (OS). iNHLs are also known to be highly radiosensitive diseases. Radio immunotherapy (RIT) approach such as 90Y-ibritumomab-tiuxetan (90YIT, Zevalin, Bayer Schering Pharma AG, Berlin, Germany) combined with high-dose chemotherapy protocols like BEAM (carmustine, etoposide, cytarabine and melphalan) were developed in an attempt to improve the antitumoral potency of the conditioning regimens. Since 2006, several studies have described promising results in relapsed or refractory NHLs with heterogeneous cohorts including iNHLs but also a majority of aggressive lymphomas.1, 2, 3, 4, 5 Only one phase II prospective study in indolent lymphomas showed a benefit of 90YIT in association with BEAM (Z-BEAM) as intensive therapy.6 There is a lack of data about the efficacy and safety of Z-BEAM conditioning regimen in iNHLs especially because of short follow-up in the published data. We report here the outcome from a cohort of high-risk iNHL treated with 90YIT added to BEAM regimen (Z-BEAM) for ASCT with sustained follow-up in a single French center.

When our first patient received Z-BEAM, the lack of scientific data precluded conclusion about the risk/benefit ratio of such intensive therapy including RIT. Considering this lack of data, the French health authority authorized in 2006 such strategy with RIT as an exceptional prescription and Zevalin was reimbursed by social security. Regarding the promising data published7 when associated with BEAM and the weak toxicity we experienced within its approved indication, we decided in 2006 to associate Zevalin with intensive chemotherapy as soon as a patient required autologous transplantation for indolent lymphoma. Thus, 14 consecutive patients suffering from iNHL/high-risk MCL in the Department of Hematology in Besancon University Hospital (France) between June 2006 and July 2009 were proposed for ASCT with Z-BEAM as the conditioning regimen. We report here the outcome of those patients. In order to stress our results, we will report at the same time a control group treated with BEAM regimen in our center and recruited between 2001 and 2009. The Table 1 shows characteristics of the both cohorts. All patients gave their informed consent to the collection and analyses of their data according to the French standards and to the declaration of Helsinki. Briefly, PBSC were collected by apheresis after mobilization with SC hematopoietic growth factor support as already described.8, 9 The transfused graft had to contain more than 4 × 106 CD34+ cells/kg to be included in our study. In Z-BEAM regimen, Rituximab (F. Hoffmann-La Roche, Basel, Switzerland) was first injected in purpose to promptly saturate all natural non-tumoral antigenic site before the radionucleotid infusion. 90YIT 15 MBq/kg (0.4 mCi/kg) infusion was administered with a maximum total dose of 1200 MBq (32mCi) in the Nuclear Medicine department within our hospital. Then BEAM regimen was administered as already described.8 The autologous graft was infused at least 24 h after the last chemotherapy administration. All patients were treated in the same conditions according to the standard practices and recommendations as described in our standard institutional protocols.10 Only supportive care may have been modified during the period study, especially for the BEAM cohort for which the first patient was treated in 2001. We defined engraftment when absolute neutrophil count is superior to 0.5 × 109/L and platelets superior to 20 × 109/L for two consecutive days.

Table 1 Patient characteristics in the Z-BEAM and BEAM groups
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Acknowledgements

We thank the medical team at the Department of Hematology in Besancon University Hospital for their contributions and all the patients for their participation.

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Authors and Affiliations

  1. Department of Hematology, University Hospital, UMR 1098, Besançon, France

    L Philippe, E Deconinck & E Daguindau

  2. Department of Oncology, University Hospital, Pointe-a-Pitre, Guadeloupe, France

    P Helias

  3. Department of Clinical methodologies, University Hospital, Besançon, France

    M Puyraveau

  4. Department of Nuclear Medicine, University Hospital, Besançon, France

    H Boulahdour

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  1. L Philippe
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Correspondence to E Daguindau.

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Philippe, L., Helias, P., Puyraveau, M. et al. Long-term follow-up of 90Y-ibritumomab-tiuxetan (90YIT) in the conditioning of autologous hematopoietic transplantation for indolent and mantle cell lymphomas in a single French center. Bone Marrow Transplant 51, 1140–1142 (2016). https://doi.org/10.1038/bmt.2016.67

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