Immunotherapy

The Lymphoma Group of The Norwegian Radium Hospital has for many years participated in multi-centre trials investigating the role of monoclonal anti-CD20 antibody treatment alone or in combination with chemotherapy or IFN-alfa. These studies have contributed to improve the treatments for various B-cell lymphomas. The following studies have been completed:
  1. MINT-study. European multicentre phase III protocol in patients < 60 years with diffuse large B-cell lymphoma IPI score 0-I, first line. Randomization between 6 courses of CHOP-21 based therapy with or without Rituximab.
  2. EORTC-20981-study. European multi-centre phase III study in patients with relapsed follicular lymphoma grade I-III. Randomization between 6 courses of CHOP21 with or without Rituximab.
  3. Rituximab/IFN-study. Nordic phase II study in indolent non-Hodgkin B-cell lymphoma. After 4 courses of Rituximab, patients with MR or PR were randomized between 4 more courses of Rituximab with or without IFN-alfa.
New studies have been started and the following are still ongoing:
  1. CRY-04-study. Nordic phase II trial for patients < 65 years with diffuse large B-cell lymphoma with IPI-score II-III. The treatment consists of 6 courses of CHOEP14 with Rituximab, followed by one course of HD-MTX and one course of HD-ARA-C. This study is chaired by dr. Harald Holte in our hospital. The study centre will be at the Department of Clinical Research The Norwegian Radium Hospital.
  2. ML-16865-study. Nordic phase III study in indolent non-Hodgkin B-cell lymphoma. Randomization between 8 courses of Rituximab with or without IFN-alfa.

Radioimmuntherapy has for many years been an area of interest in our group. Ex-vivo studies have been performed with the alfa-emittor 211At coupled to anti-CD20 monoclonal antibody in B-cell lymphoma cells (Thesis by dr. Ellen Aurlien 2004: “Alfa-particle based radioimmunotherapy”). In addition, the implementation of beta-emittor 90Y-coupled anti-CD20 radioimmunotherapy in the treatment of B-cell lymphomas in clinical trials are ongoing or starting soon. See below:
  1. Zevalin-study. European/Canadian phase III multicentre study in first line treatment of follicular lymphoma. Patients in PR or CR after induction chemotherapy are randomized to radioimmunotherapy versus follow-up alone.
  2. Nordic MCL-III-study. High-dose therapy with autologous stem cell support in first line treatment of mantle cell lymphoma. Yttrium-labeled ibritumomab tiuxetan combined with BEAM or BEAC in order to improve results for patients not in CR after induction therapy.
A new Nordic phase II study for first line therapy in mantle cell lymphoma is now almost ready to start (see above). This study involves the use of Zevalin as part of the conditioning before autologous stem cell transplant in patients who do not reach CR after induction immunochemotherapy. The aim is to improve results from a previous Nordic phase II study, which showed that patients not in CR before transplant fare less well. This protocol is written by dr. Arne Kolstad in our hospital who will be the principal investigator. The study centre will be at the Department of Clinical Research The Norwegian Radium Hospital.

Allogeneic stem cell transplantation with reduced conditioning is evolving as a novel strategy for immunotherapy for many haematological malignancies. The graft-versus-lymphoma effect may be important to cure patients which until recently were considered non-curable by conventional treatments. Our group has for the last years developed a mutual research collaboration with Dr. Dan Fowlers group at the NCI, Bethesda US. Norwegian patients have been admitted to NCI for inclusion in protocols aimed to prevent GVHD by advanced T-cell manipulations. As a result of the close cooperation between NCI and our group, a new study has now been initiated which we will participate in. Ex-vivo manipulated T-cells (Th2-cells cultured in rapamycine) from donor together with oral rapamycin will be given after transplant in order to prevent GVHD. The is a three-armed randomized study:
“Randomized study of sirolimus (rapamycin) generated donor Th2-cells and in vivo sirolimus for GVHD prevention after allogeneic HSCT for hematologic malignancy”
Dr. Arne Kolstad in our group will be the investigator in Norway for this study, which will only take place at NCI and The Norwegian Radium Hospital. Our aim is to develop further protocols applying tumour vaccine strategies combined with this approach in the coming years.

The Lymphoma Group at The Norwegian Radium Hospital have plans to develop new studies involving translational research in the field of immunotherapy, in collaboration with the strong milieu for basal immunology at our institution.
 
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