Incidence of Altered Biodistribution Detected by Indium 111 (¹¹¹In) Imaging Prior to Yttrium 90 (⁹⁰Y) Ibritumomab Tiuxetan (Zevalin®) Radioimmunotherapy: Results from a Zevalin Imaging Registry.

Background: The yttrium 90 (⁹⁰Y) ibritumomab tiuxetan (Zevalin^Ò) therapeutic regimen consists of rituximab 250 mg/m² on day 1 and 8, followed by indium 111 (¹¹¹In) ibritumomab tiuxetan for imaging on Day 1 and ⁹⁰Y ibritumomab tiuxetan for therapy on day 8. Indium 111 ibritumomab tiuxetan scans are performed as an added safety measure to ensure appropriate biodistribution of the radiolabeled antibody. Two scans are required at 2–24 hours and 48–72 hours, with an optional third scan performed at 90–120 hours after ¹¹¹In ibritumomab tiuxetan. At the time of market launch, approximately 400 clinical trial patients had undergone ¹¹¹In ibritumomab tiuxetan imaging (or full dosimetry) prior to receiving ⁹⁰Y ibritumomab tiuxetan treatment and, of these, only 1 case did not receive treatment because of altered biodistribution. A Zevalin imaging registry was established by Biogen Idec to collect additional information on treatment decisions based on imaging results.

Methods: The registry collected de-identified treatment information from patients who received commercial ¹¹¹In ibritumomab tiuxetan from 27 March 2002 through 31 March 2003. Survey data were collected on 953 of an estimated 1144–1192 patients who initiated ibritumomab tiuxetan therapy (case capture rate 80–83%).

Results: Thirty-eight cases were reported in which a no-treatment decision was made following ¹¹¹In ibritumomab tiuxetan imaging (4.0% of all cases captured); 16 of these were based on imaging rationale, and 22 based on medical issues. Twelve of the 16 imaging cases met the criteria for altered biodistribution (incidence 1.2%). Of these 12 cases, 6 cases (0.63%) were suspected to be true altered biodistribution (4 prominent bone marrow, 1 pneumonia known to be present on CXR prior to imaging, and 1 case of increased renal uptake for which there is insufficient information to rule out a disease-related cause), and 6 cases (0.63%) appeared to be the results of the use of a ¹¹¹In ibritumomab tiuxetan radiolabeling procedure that varied considerably from that described in the package insert. (After retraining the radiopharmacy using the unapproved procedure, no additional cases have been reported.) All cases of altered biodistribution were detected on scan 1, performed 2–24 hours following ¹¹¹In ibritumomab tiuxetan administration. There were 22 instances in which no-treatment decisions were made based on medical issues. This represents an incidence of 2.3% of the 953 cases collected in the registry. These cases can be divided into 3 categories: patients with a known contraindication to ibritumomab tiuxetan therapy detected after imaging (n = 2); patients with an expected biodistribution but with a rapid change in clinical condition precluding treatment (n = 19); and 1 other case (physician decision not to treat outside the labeled indication).

Conclusion: The reporting rate of true altered biodistribution was <0.7% in an ibritumomab tiuxetan imaging registry that collected treatment decisions on approximately 80% of all patients treated commercially during the first year after the drug was approved. All cases of altered biodistribution were apparent on the first scan performed 2–24 hours after ¹¹¹In ibritumomab tiuxetan administration.