Dosimetry of ⁹⁰Y-Ibritumomab Tiuxetan as Consolidation of First Remission in Advanced-Stage Follicular Lymphoma: Results from the International Phase 3 First-Line Indolent Trial

Abstract

The objective of this analysis was to assess the radiation exposure associated with 90 Y-ibritumomab tiuxetan when used as consolidation therapy in adults with low or minimal tumor burden after first-line therapy of advanced follicular lymphoma (FL). Methods:The patients who were enrolled in the phase 3 firstline indolent trial were 18 y or older, with CD20 1 grade 1 or 2 stage III or IV FL, and a partial response, complete response, or unconfirmed complete response to first-line chemotherapy. The patients were allocated randomly to receive a single infusion of unlabeled rituximab 250 mg/m 2 on day 27 and consolidation on day 0 with a single dose of 90 Y-ibritumomab tiuxetan, 14.8 MBq/kg, immediately after unlabeled rituximab, 250 mg/m 2 , or no further treatment. On day 27, a subset of patients received an injection of 185 MBq of 111 In-ibritumomab tiuxetan immediately after unlabeled rituximab, 250 mg/m 2 , for central dosimetry analysis. Correlations were assessed between organ radiation absorbed dose and toxicity, body weight, body mass index, and progression-free survival. Results: Central dosimetry evaluations were available from 57 of 70 patients. Median radiation absorbed doses were 100 cGy (range, 28-327 cGy) for the red marrow and 72 cGy (range, 46-106 cGy) for the whole body. Radiation absorbed doses did not differ significantly between patients who had a partial response or complete response to initial therapy. Progression-free survival correlated significantly with the whole-body (r 5 0.4401; P 5 0.0006) and bone marrow (r 5 0.2976; P 5 0.0246) radiation dose. Body weight was significantly negatively correlated with whole-body radiation dose (r 5 20.4971; P , 0.0001). Neither the whole-body radiation dose nor the bone marrow radiation dose correlated with hematologic toxicity. Conclusion: In patients with low or minimal residual tumor burden after first-line chemotherapy of advanced FL, wholebody and bone marrow exposure after 90 Y-ibritumomab tiuxetan consolidation showed a significant positive correlation with progression-free survival, whereas dosimetric data could not predict hematologic toxicity.

Radioimmunotherapy with Radretumab in Patients with Relapsed Hematologic Malignancies

“…The severity of acute hematologic toxicity could not be predicted by the BM provisional dose, in particular in patients with a compromised marrow reserve. This finding is in line with earlier reports on noncorrelation of dosimetry results with hematologic toxicity after 131 I-tositumomab and 90 Y-ibritumomab tiuxetan radioimmunotherapy (18,19), irrespective of the dosimetric approach used. With these agents, elapsed time after the last chemotherapy was the only factor that predicted hematologic toxicity after radioimmunotherapy (20).…”

90Y-ibritumomab tiuxetan therapy in allogeneic transplantation in B-cell lymphoma with extensive marrow involvement and chronic lymphocytic leukemia

“…In our study, we did not evaluate the relationship between bone marrow uptake and marrow toxicity, since previous studies have shown that the toxicity depends more on the bone marrow reserve than on the radiotracer distribution (7, 8, 9, 11). Nevertheless, we analyzed the ability to predict bone marrow involvement by lymphoma based on image analysis.…”

“…However, this is not correlated with the red marrow or total body radiation absorbed dose estimates or with effective half-life or residence time of 90 Y- ibritumomab tiuxetan in blood, suggesting that hematologic toxicity is dependent on bone marrow reserve (7, 8, 9). Based on these findings, it is considered safe to administer 90 Yibritumomab tiuxetan in standard low dose without pre-treatment dosimetry (10, 11). However, pre-treatment imaging with 111 In- ibritumomab tiuxetan was used for clinical purposes until recently in the USA (and is still used in Switzerland and Japan) to guard against the hypothetical risk of altered biodistribution of the radioimmunoconjugate which could cause unintended end organ damage.…”

Novel Antibody-Based Proteins for Cancer Immunotherapy

“…More recently and based on results from Phase II/III clinical trials [43-46] regulatory organisms in USA and EU (FDA and EMEA, respectively) licensed the use of 90 Y-IT as a first-line consolidation therapy in follicular NHL patients who show a favorable response to induction with a combined chemo/immunotherapy protocol (http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000547/WC500049469.pdf) [47,48]. …”