Oncotarget

Research Papers:

Myeloablative Anti-CD20 Radioimmunotherapy +/- High-Dose Chemotherapy Followed by Autologous Stem Cell Support for Relapsed/Refractory B-Cell Lymphoma Results in Excellent Long-Term Survival

Julia Y. Wagner, Kathleen Schwarz, Susanne Schreiber, Burkhard Schmidt, Hans-Jürgen Wester, Markus Schwaiger, Christian Peschel, Christoph von Schilling, Klemens Scheidhauer and Ulrich Keller _

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Oncotarget. 2013; 4:899-910. https://doi.org/10.18632/oncotarget.1037

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Abstract

Julia Y Wagner1,*, Kathleen Schwarz1,2,*, Susanne Schreiber1, Burkhard Schmidt1, Hans-Jürgen Wester3,4, Markus Schwaiger3, Christian Peschel1, Christoph von Schilling1,2, Klemens Scheidhauer3,*, and Ulrich Keller1,*

1 III. Medical Department, Technische Universität München, Munich, Germany;

2 Hematology and Oncology, Klinikum Freising, Freising, Germany;

3 Nuclear Medicine Department, Technische Universität München, Munich, Germany;

4 Pharmaceutical Radiochemistry, Technische Universität München, Garching, Germany

* These authors contributed equally

Correspondence:

Ulrich Keller, email:

Klemens Scheidhauer, email:

Keywords: Non-Hodgkin lymphoma; Radioimmunotherapy; CD20; High-dose chemotherapy;Autologous stem cell transplantation

Received: May 17, 2013 Accepted: June 11, 2013 Published: June 12, 2013

Abstract

Background: Radioimmunotherapy (RIT) has been used to treat relapsed/refractory CD20+ Non-Hodgkin lymphoma (NHL). Myeloablative anti-CD20 RIT followed by autologous stem cell infusion (ASCT) enables high radiation doses to lymphoma sites. We performed a phase I/II trial to assess feasibility and survival.

Methods: Twenty-three patients with relapsed/refractory NHL without complete remission (CR) to salvage chemotherapy were enrolled to evaluate RIT with Iodine-131 labelled rituximab (131I-rituximab) in a myeloablative setting. Biodistribution and dosimetric studies were performed to determine 131I activity required to induce a total body dose of 21-27Gy to critical organs. In 6/23 patients RIT was combined with high-dose chemotherapy. 8/23 patients received a sequential high-dose chemotherapy with a second ASCT. The median follow-up is 9.5 years.

Results: 6.956-19.425GBq of 131I was delivered to achieve the limiting organ dose to lungs or kidneys. No grade III/IV non-hematologic toxicity was seen with RIT alone. Significant grade III/IV toxicity (mucositis, fever, infection, one therapy related death) was observed in patients treated with RIT combined with high-dose chemotherapy. The overall response rate was 87% (64% CR). The median progression-free (PFS) and overall survival (OS) is 47.5 and 101.5 months. An international prognostic index score >1 was predictive for OS.

Conclusion: Myeloablative RIT with 131I-rituximab followed by ASCT is feasible, well-tolerated and effective in high risk CD20+ NHL. Combination of RIT and high-dose chemotherapy increased toxicity significantly. Long-term results for PFS and OS are encouraging.


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