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 ((111)In) for imaging and dosimetry and yttrium-90 ((90)Y) 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 (111)In-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) (111)In-Zevalin on Day 0, evaluated with dosimetry, and then given a therapeutic dose of 0.4 mCi/kg (15 MBq/kg) (90)Y-Zevalin on Day 7. Both Zevalin doses were preceded by an infusion of 250 mg/m(2) rituximab to clear peripheral B cells and improve Zevalin biodistribution. Residence times for (90)Y in blood and major organs were estimated from (111)In 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 (90)Y-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.
Wiseman
Gregory A
GA
Division of Nuclear Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA. gwiseman@mayo.edu
Leigh
Bryan
B
Erwin
William D
WD
Lamonica
Dominick
D
Kornmehl
Ellen
E
Spies
Stewart M
SM
Silverman
Daniel H S
DH
Witzig
Thomas E
TE
Sparks
Richard B
RB
White
Christine A
CA
D000328:Adult; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000188:drug therapy*; D016499:Radioimmunotherapy; D011874:Radiometry; D000069283:Rituximab
D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; C422802:ibritumomab tiuxetan