Baseline peripheral blood B-cell levels correlate with disease-free interval and response to zevalin radioimmunotherapy of relapsed non-hodgkin's lymphoma

T. E. Witzig*, L. I. Gordon, B. R. Leigh, G. A. Wiseman, C. Emmanouilides, M. S. Czuczman, J. L. Murray, C. Zhang, A. J. Grillo-Lopez, C. A. White

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Zevalin (ibritumomab tiuxetan) is an anti-CD20 murine IgG, kappa monoclonal antibody conjugated to the linker tiuxetan, which securely chelates 90Y for radioimmunotherapy of NHL. The therapeutic dose of 90Y Zevalin is preceded by two weekly infusions of 250 mg/ m2 rituximab, the unlabeled chimeric anti-CD20 antibody, to clear peripheral B-cells and improve biodistribution of the radiolabeled antibody. The purpose of this analysis was to assess the relationship between pretreatment B-cell levels (CD19+) and the safety, efficacy, and biodistribution of Zevalin. Data on 130 patients from two Phase III clinical trials of 0.4 mCi/kg 90Y Zevalin were combined. One study included 73 rituximab-naive patients and the other included 57 rituximab-refractory patients. All patients had relapsed or refractory low grade, follicular or transformed NHL with a baseline platelet count > 150,000/mm3, ANC > 1500/mmm3, bone marrow involvement < 25 %, and no prior bone marrow or stem cell transplant. Using the International Workshop NHL Response Criteria, the overall response rate was 74% in this heavily pretreated population (1-9 prior therapies). Baseline peripheral blood B-cell levels were available for 125 of the 130 patients. B-cell levels were undetectable in 19% of patients, low (<32/mm3) in 28%, and normal or high (>32/mm3) in 53%. Patients with undetectable B-cell levels had a significantly lower overall response rate than those with low or normal/high B-cell levels (45% vs. 83% vs. 77%, p=0.007). As expected, the interval between last NHL therapy and Zevalin RIT was significantly shorter for patients with undetectable B-cell levels as compared to those with low or normal/high B-cell levels (4 months vs. 15 months vs. 21 months, p < 0.001). No significant differences in hématologie or non-hematologic toxicity were detected between the three groups. In addition, imaging and dosimetry showed no evidence of unfavorable biodistribution in patients with undetectable B-cell levels. These results indicate that undetectable pretreatment B-cell levels in patients with relapsed NHL are a surrogate for short disease-free interval and poor prognosis. Despite these findings, the Zevalin regimen can be safely applied to this unfavorable patient population with excellent anti-tumor activity.

Original languageEnglish (US)
Pages (from-to)252b
JournalBlood
Volume96
Issue number11 PART II
StatePublished - 2000

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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