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Initial Experience with Tositumomab and I-131-Labeled Tositumomab for Treatment of Relapsed/Refractory Hodgkin Lymphoma

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Abstract

Purpose

To determine the maximum tolerated dose (MTD) of [131I]tositumomab in patients with refractory/recurrent Hodgkin lymphoma (HL) and to preliminarily determine if [131I]tositumomab has activity against HL and if positron emission tomography (PET) with 2-deoxy-2-[18F]fluoro-D-glucose ([18F]DG) performed 6 weeks post-therapy predicted 12-week response.

Procedures

Separate dose-finding studies were performed for patients with and without prior transplant. A single therapeutic total body radiation dose (TBD) of [131I]tositumomab was administered. TBD was escalated/de-escalated based on dose-limiting hematologic toxicity (DLT) using a modified continual reassessment method. [18F]DG-PET/CT scans were performed at baseline and 6 and 12 weeks post therapy.

Results

Twelve patients (nine classical HL, three lymphocyte-predominant [LP] HL) completed two dosing levels (n = 3 each) in the post-transplant (55 cGy, 79 cGy) and no transplant (75 cGy, 87 cGy) groups. Hematologic toxicities were common and transient. Twelve weeks after [131I]tositumomab, 10 patients progressed and two with LPHL achieved complete response. [18F]DG-PET/CT at 6 weeks post therapy appeared more predictive than CT at 6 weeks of a response at 12 weeks.

Conclusions

Tositumomab and [131I]tositumomab was well-tolerated in patients with relapsed/refractory HL. Complete responses in LPHL support a therapeutic effect in this subtype. Early metabolic response assessments by [18F]DG-PET in HL after radioimmunotherapy appear to be more predictive than purely anatomic assessments.

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Acknowledgments

This study was supported by GlaxoSmithKline and Johns Hopkins SPORE in Lymphoma grant #1 P50 CA96888-04 (PI Ambinder). The role of GlaxoSmithKline was financial support of the study. Study design, collection, analysis and interpretation of data, preparation of the manuscript and decision for publication were the roles of the investigators. The authors thank Mrs. Judy Buchanan for her assistance in the preparation of this manuscript.

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Author notes

  1. Heather Jacene

    Present address: Department of Imaging, Dana-Farber Cancer Institute, 450 Brookline Avenue, DL203, Boston, MA, 02215, USA

  2. John Crandall & Richard L. Wahl

    Present address: Mallinkrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO, USA

Authors and Affiliations

  1. Division of Nuclear Medicine, Department of Radiology, Johns Hopkins University, Baltimore, MD, USA

    Heather Jacene, John Crandall, Donna Serena, Wayne Kasecamp & Richard L. Wahl

  2. Department of Oncology, Johns Hopkins University, Baltimore, MD, USA

    Yvette L. Kasamon, Richard F. Ambinder & Richard L. Wahl

  3. Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai, Los Angeles, CA, USA

    Steven Piantadosi

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  1. Heather Jacene
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Corresponding author

Correspondence to Heather Jacene.

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Conflict of Interest Statement

The authors declare that they have no conflict of interest.

Funding

This study was supported by GlaxoSmithKline and Johns Hopkins SPORE in Lymphoma grant #1 P50 CA96888-04 (PI Ambinder).

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Jacene, H., Crandall, J., Kasamon, Y.L. et al. Initial Experience with Tositumomab and I-131-Labeled Tositumomab for Treatment of Relapsed/Refractory Hodgkin Lymphoma. Mol Imaging Biol 19, 429–436 (2017). https://doi.org/10.1007/s11307-016-1019-9

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  • DOI: https://doi.org/10.1007/s11307-016-1019-9

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