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Survival benefit associated with human anti-mouse antibody (HAMA) in patients with B-cell malignancies

Cancer Immunology, Immunotherapy volume 55, pages 1451–1458 (2006)Cite this article

Abstract

Background: About one-third of patients with relapsed B-cell malignancies develop human anti-mouse antibody (HAMA) following mouse antibody treatment. The purpose of this study was to assess the relationship between HAMA and survival in patients given a mouse anti-lymphoma monoclonal antibody (mAb), Lym-1, directed against a unique epitope of HLA-DR antigen that is up-regulated on malignant B-cells. Methods: ELISA was used to quantify HAMA in 51 patients with B-cell malignancies treated with iodine-131 (131I) labeled Lym-1. Sera were collected prior to and following radioimmunotherapy (RIT) with 131I-Lym-1 until documented to be HAMA negative or throughout lifetime. Univariate, then multivariate analyses including other risk factors, were used to analyze the relationship of HAMA to survival. The relationships of HAMA to prior chemotherapies and to absolute lymphocyte counts prior to RIT were also assessed. Results: Eighteen of 51 patients (35%) developed HAMA following RIT (range of ultimate maximum titers, 6.6–1,802 μg/ml). Using the time dependent Cox proportional hazards model, maximum HAMA titers were associated with survival (P=0.02). HAMA continued to be significant for survival in multivariate analyses that included known risk factors. In Landmark analysis of 39 patients that survived at least 16 weeks, median survival of patients with HAMA less than 5 μg/ml was 61 versus 103 weeks for patients with HAMA equal or greater than 5 μg/ml at 16 weeks (P=0.02). The median survival of the five patients with highest maximum HAMA titers was 244 weeks. At 16 weeks, there was an inverse correlation between the maximum HAMA titer and the number of previous chemotherapies (P<0.003). Absolute lymphocyte counts prior to 131I-Lym-1 treatment for patients that seroconverted were higher than those for patients that did not seroconvert (P=0.01). Conclusions: Patients with B-cell malignancies that developed high HAMA titers had longer survival that was not explained by risk factors or histologic grade, suggesting the importance of the immune system.

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Acknowledgments

This research was supported by grants from the National Cancer Institute (PHS CA 47829) and the Department of Energy (DE FG03-84ER60233). I.A. was supported by a grant from the Hospital San Jaime, Torrevieja, Alicante (Spain).

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Affiliations

  1. Department of Radiotherapy, Hospital San Jaime, Torrevieja, 03180, Alicante, Spain

    Ignacio Azinovic

  2. Davis Medical Center, Department of Internal Medicine, University of California, Sacramento, CA, 95816, USA

    Gerald L. DeNardo, Gary Mirick, Desiree Goldstein, Bonnie M. Bradt & Sally J. DeNardo

  3. Department of Neurological Surgery, University of California at San Francisco, San Francisco, CA, 94143, USA

    Kathleen R. Lamborn

  4. Molecular Cancer Institute, Davis Medical Center, University of California, 1508 Alhambra Boulevard, Room 3100, Sacramento, CA, 95816, USA

    Gerald L. DeNardo

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  1. Ignacio Azinovic
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  2. Gerald L. DeNardo
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Correspondence to Gerald L. DeNardo.

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Azinovic, I., DeNardo, G.L., Lamborn, K.R. et al. Survival benefit associated with human anti-mouse antibody (HAMA) in patients with B-cell malignancies. Cancer Immunol Immunother 55, 1451–1458 (2006). https://doi.org/10.1007/s00262-006-0148-4

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  • DOI: https://doi.org/10.1007/s00262-006-0148-4

Keywords

  • Non-Hodgkin’s lymphoma
  • Radioimmunotherapy
  • Survival
  • Human anti-mouse antibody
  • Monoclonal antibody
  • HLA-DR