Zevalin (ibritumomab tiuxetan) is an anti-CD20 murine IgG1 kappa monoclonal antibody conjugated to the linker tiuxetan (MX-DTPA), which securely chelates 90Y for RIT. 90Y Zevalin is under investigation for the treatment of relapsed or refractory B-cell NHL. The therapeutic dose of 90Y Zevalin is preceded by two weekly infusions of rituximab, an unlabeled chimeric anti-CD20 antibody, to clear peripheral B cells and improve biodistribution of the radiolabeled antibody. The purpose of this analysis was to evaluate the effect of the time interval between the second rituximab infusion and the 90Y Zevalin injection on the safety and efficacy of Zevalin RIT. Data on this time interval were available for 203 patients from four Phase I-I1I multicenter clinical trials of 0.2-0.4 mCi/kg Zevalin RIT for NHL. All patients had baseline platelet counts > 100,000, ANC > 1500, bone marrow involvement < 25%, and no prior myeloablative therapy. Patients had received between one and nine prior NHL therapies. The overall response rate by International Workshop NHL Response Criteria for this refractory population with advanced disease was 69%. Toxicity was primarily hématologie, transient, and reversible. The time interval between the second rituximab infusion and the Zevalin injection was < 1 hour in 61% of patients (123/203), between 1 - 4 hours in 35% (72/203), and between 4 - 48 hours in 4% (8/203). The table below shows that the overall response rate and the incidence of grade 4 hématologie toxicity were not significantly different between the three groups of patients. Rituximab-Zevalin Overall Grade 4 Grade 4 Time Interval Response Rate Thrombocytopenia Neutropenia < 1 hr 66% (81/123) 9% (11/123) 29% (36/123) 1-4 hrs 71% (51/72) 10% (7/72) 33% (24/72) >4hrs 88% (7/8) 0% (0/8) 63% (5/8) P value 0.41 0.99 0.17 Fisher's exact 2 tailed test These findings demonstrate that time intervals of up to four hours between completion of the second rituximab infusion and delivery of the WY Zevalin injection did not significantly reduce the likelihood of response to therapy or increase the risk for hematologic toxicity. This information should reassure patients and physicians that moderate delays for patient transportation from an outpatient rituximab infusion center to a nuclear medicine or radiation oncology department for administration of the Zevalin dose will not adversely affect therapy results.
|Original language||English (US)|
|Issue number||11 PART II|
|State||Published - Dec 1 2000|
ASJC Scopus subject areas
- Cell Biology