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Absorbed dose and biologically effective dose in patients with high-risk non-Hodgkin’s lymphoma treated with high-activity myeloablative 90Y-ibritumomab tiuxetan (Zevalin®)

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Abstract

Purpose

The aim of this study was to carry out two different dose estimation approaches in patients with non-Hodgkin’s lymphoma (NHL) treated with a myeloablative amount of 90Y-labelled ibritumomab tiuxetan (Zevalin®) in an open-label dose escalation study.

Methods

Twenty-seven patients with relapsed/refractory or de novo high-risk NHL receiving one myeloablative dose of 90Y-ibritumomab tiuxetan followed by tandem stem cell reinfusion were evaluated for dose estimate. The injected activity was 30 MBq/kg in 12 patients and 45 MBq/kg in 15 patients. Dose estimation was performed 1 week prior to 90Y-ibritumomab tiuxetan by injection of 111In-ibritumomab tiuxetan (median activity: 200 MBq). The absorbed dose (D) and the biologically effective dose (BED) were calculated.

Results

The absorbed doses per unit activity (Gy/GBq) were [median (range)]: heart wall 4.6 (2.5–9.7), kidneys 5.1 (2.8–10.5), liver 6.1 (3.9–10.4), lungs 2.9 (1.5–6.8), red marrow 1.0 (0.5–1.7), spleen 7.0 (1.5–14.4) and testes 4.9 (2.9–16.7). The absorbed dose (Gy) for the 15 patients treated with 45 MBq/kg were: heart wall 17.0 (8.7–25.4), kidneys 17.1 (7.9–22.4), liver 20.8 (15.4–28.3), lungs 8.1 (5.4–11.4), red marrow 3.1 (2.0–4.0), spleen 26.2 (17.0–35.6) and testes 17.3 (9.0–28.4). At the highest activities the acute haematological toxicity was mild or moderate and of very short duration, and it was independent of the red marrow absorbed dose. No secondary malignancy or treatment-related myelodysplastic syndrome was observed. No non-haematological toxicity (liver, kidney, lung) was observed during a follow-up period of 24–48 months.

Conclusion

The use of 45 MBq/kg of 90Y-ibritumomab tiuxetan in association with stem cell autografting resulted in patients being free of toxicity in non-haematological organs. These clinical findings were in complete agreement with our dose estimations, considering both organ doses and BED values.

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Notes

  1. After completion of this dosimetric study, 57 patients were treated with 45 MBq/kg in an ongoing clinical study without dose estimation, for a total of 72 treatments with 45 MBq/kg.

  2. After completion of this dosimetric study, a total of 72 patients were treated with 45 MBq/kg and no extrahaematological toxicity was observed.

  3. In our limited experience with an anti-α-folate receptor immunoconjugate developed in our Institute (90Y-Mov18) for the treatment of ovarian cancer, we observed a similar mismatch between low blood-based red marrow dose and high haematological toxicity in the presence of visible spine.

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Acknowledgments

Supported in part by grants from Ministero dell’Università e della Ricerca (Rome, Italy), Ministero della Salute (Rome, Italy), Alleanza Contro il Cancro (Rome, Italy), and Michelangelo Foundation for Advances in Cancer Research and Treatment (Milano, Italy).

We thank our technologists Ms. Monica Testoni and Ms. Rossana Pavesi for patient scanning, and Dr. Mauro Carrara and Dr. Stefano Tomatis of the Health Physics Division of our Institute for useful discussions about data analysis.

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Chiesa, C., Botta, F., Coliva, A. et al. Absorbed dose and biologically effective dose in patients with high-risk non-Hodgkin’s lymphoma treated with high-activity myeloablative 90Y-ibritumomab tiuxetan (Zevalin®). Eur J Nucl Med Mol Imaging 36, 1745–1757 (2009). https://doi.org/10.1007/s00259-009-1141-x

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