Radiation dosimetry results for Zevalin radioimmunotherapy of rituximab-refractory non-Hodgkin lymphoma

BACKGROUND. Zevalin consists of a murine anti-CD20 monoclonal antibody (ibritumomab) conjugated to the linker-chelator tiuxetan, which securely chelates indium-111 (¹¹¹In) for imaging and dosimetry and yttrium-90 (⁹⁰Y) for radioimmunotherapy (RIT). Previous trials involving rituximab-naïve patients have demonstrated excellent targeting of Zevalin to CD20+ B-cell non-Hodgkin lymphoma with minimal uptake in normal organs. The purpose of this trial was to perform ¹¹¹In-Zevalin imaging in patients with rituximab-refractory tumors to determine normal organ dosimetry. METHODS. Twenty-seven patients were given an imaging dose of 5 mCi (185 MBq) ¹¹¹In-Zevalin on Day 0, evaluated with dosimetry, and then given a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) ⁹⁰Y-Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m² rituximab to clear peripheral B cells and improve Zevalin biodistribution. Residence times for ⁹⁰Y in blood and major organs were estimated from ¹¹¹In biodistribution, and the MIRDOSE3 computer software program was used to calculate absorbed radiation doses to organs and red marrow. RESULTS. Median estimated absorbed radiation doses from ⁹⁰Y-Zevalin were 8.1 Gray (Gy) (range, 4.2-23.0 Gy) to the spleen, 5.1 Gy (range, 2.6-12.0 Gy) to the liver, 2.0 Gy (range, 1.4-5.3 Gy) to the lungs, 0.22 Gy (range, < 0.01-0.66 Gy) to the kidneys, and 0.74 Gy (range, 0.29-1.2 Gy) to the red marrow. These results are consistent with those from earlier Zevalin trials in rituximab-naïve patients. Hematologic toxicity was manageable and did not correlate with estimates of red marrow or total-body absorbed radiation dose. CONCLUSIONS. Zevalin treatment of rituximab-refractory follicular NHL patients at 0.4 mCi/kg resulted in acceptable estimates of absorbed radiation dose to organs, similar to those observed in other Zevalin-treated populations.