Observational Retrospective Study of Altered Biodistribution of Tositumomab and ¹³¹I-Tositumomab

Study Design

This was an observational, retrospective study (GlaxoSmithKline study BEX114606) with anonymized data from patients who received the dosimetric dose of TST/¹³¹I-TST in the commercial setting between June 2003 and February 2010. Commercial orders for TST/¹³¹I-TST were retrospectively assessed to determine the total number of patients who received the dosimetric dose, the reasons for cancellation of the therapeutic dose, and the frequency of patients with a reported altered biodistribution. The frequency of cancellations was summarized according to medical reasons or other reasons. Whole-body γ-camera images and dosimetry calculations of the TBRT of patients who did not receive the therapeutic dose because of altered biodistribution were evaluated by an independent nuclear medicine physician. Images from patients with an expected biodistribution were not independently reviewed.

TST/¹³¹I-TST was administered according to its prescribing information (1). The dosimetric dose consisted of 450 mg of unlabeled TST (in 50 mL of 0.9% NaCl solution) administered intravenously over 1 h, followed immediately by 35 mg of TST labeled with 185 ± 18.5 MBq (5 ± 0.5 mCi) of ¹³¹I (in 30 mL of 0.9% NaCl solution) administered intravenously over 20 min. The therapeutic dose consisted of the same unlabeled TST dose, followed by 35 mg of TST labeled with a patient-specific activity of ¹³¹I (in 30 mL of 0.9% NaCl solution). The required activity of ¹³¹I to deliver the desired whole-body dose of radiation was calculated according to the patient platelet count: 65 cGy if the platelet count was 100,000–149,999/mm³; 75 cGy if the platelet count was at least 150,000/mm³ (1).

Assessment of Dosimetry and Biodistribution

After the dosimetric dose, whole-body γ-camera counts and whole-body γ-camera images were obtained at 3 time points: within 1 h of infusion and before urination, 2–4 d after infusion of the dosimetric dose, and 6–7 d after infusion of the dosimetric dose. TBRT was the time in hours at which the activity was 37% of that at time zero; the activity was measured by whole-body γ-camera counts.

Data Collection and Management

Records of completed and cancelled TST/¹³¹I-TST commercial orders were maintained by the GlaxoSmithKline Speciality Service Centre using the Bexxar Operations and Order Tracking System. Reasons for cancellation of the therapeutic dose were prospectively recorded by the GlaxoSmithKline Speciality Service Centre at the time of cancellation and retrospectively confirmed by the treatment site investigator. GlaxoSmithKline used anonymized dosimetry calculations and γ-camera images from the medical centers to assess the dosimetry and biodistribution for reported cases of altered ¹³¹I-TST biodistribution.

BioClinica, Inc., managed the image files and coordinated the independent review of biodistribution.

Independent Review of γ-Camera Images and Time Calculations

Whole-body γ-camera images were independently reviewed by a nuclear medicine physician who did not know the results of the original biodistribution assessment performed at the treatment sites and did not receive patient dosimetry data. The independent reviewer prepared a description of the ¹³¹I-TST biodistribution at each of the 3 time points examined for each subject and, on the basis of criteria in the prescribing information (Table 1) (1), determined whether the ¹³¹I-TST biodistribution was expected or altered.

The TBRT of ¹³¹I-TST after administration of the dosimetric dose was validated by an independent reviewer in patients deemed to have an altered biodistribution. An altered biodistribution was defined as a TBRT of less than 50 h or more than 150 h (1).