Zevalin consists of a murine IgG1 kappa monoclonal antibody against CD20 (ibritumomab) conjugated to the linker-chelator tiuxetan (MX-DTPA). A simple radioincorporation process allows stable chelation of the pure beta-emitting radioisotope 90Y to Zevalin. The resulting radioimmunoconjugate permits targeted delivery of high energy ionizing radiation. The Zevalin regimen involves pretreatment with two doses of rituximab (250 mg/m2) one week apart, followed by 0.4 mCi/kg (0.3 mCi/kg in patients with mild thrombocytopenia; maximum dose 32 mCi) of 90Y Zevalin. Zevalin targets the CD20 antigen, which is found on > 95% of B cell malignancies as well as on non-malignant B cells from the pre-B cell stage through the mature stage but not on stem cells. The mechanism of action includes induction of apoptosis by ibritumomab and radiolysis of targeted and neighboring cells up to a distance of X90 = 5 mm. As with rituximab, which is the chimeric derivative of ibritumomab, therapy with 90Y Zevalin results in a prompt depletion of the CD19+/CD20+ B cell compartment. To evaluate whether the bystander radiation of 90Y Zevalin targets immune cell compartments other than B cells, we used flow cytometry to determine the numbers of circulating B cells, T cells and NK cells in 211 patients treated on 4 trials of Zevalin therapy. Peripheral blood was sampled at baseline, 4 and 12 weeks after therapy, and at months 6,9 and 12. As expected, the median number of circulating CD19+/CD20+ B cells promptly fell below the level of detection but recovered into the normal range approximately 6 months after therapy, although median serum immunoglobulin levels (IgA, IgG, and IgM) remained stable throughout this period. There was no effect on T cells. The median number of both circulating CD3+/CD4+ and CD3+/CD8+ T cells remained within the normal range. The median number of circulating CD3-/CD16+/CD56+ Natural Killer (NK) cells did fall below normal at the 4 week time point (median 50.5K cells/mm3; normal 60-810K cells/ mm3), but was back in the normal range by week 12 and remained normal throughout the remainder of first year after therapy. Of note, baseline levels were near the low end of normal (132K cells/mm3). Thus 90Y Zevalin targeted radioimmunotherapy reversibly depletes CD19+/CD20+ B cells but does not significantly affect the numbers of circulating T cells and NK cells.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - 2000|
ASJC Scopus subject areas
- Cell Biology