Yttrium-90 ibritumomab tiuxetan doses calculated to deliver up to 15 Gy to critical organs may be safely combined with high-dose BEAM and autologous transplantation in relapsed or refractory B-cell non-hodgkin's lymphoma

Jane N. Winter, David J. Inwards, Stewart Spies, Gregory Wiseman, David Patton, William Erwin, Alfred W. Rademaker, Bing Bing Weitner, Stephanie F. Williams, Martin S. Tallman, Ivana Micallef, Jayesh Mehta, Seema Singhal, Andrew M. Evens, Michael Zimmer, Arturo Molina, Christine A. White, Leo I. Gordon

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Abstract

Purpose To determine the maximum-tolerated radiation-absorbed dose(RAD) to critical organs delivered by yttrium-90(90Y) ibritumomab tiuxetan in combination with high-dose carmustine, etoposide, cytarabine, and melphalan(BEAM) chemotherapy with utologous transplantation. Patients and Methods Eligible patients had relapsed or refractory CD20+ non-Hodgkin's lymphoma(NHL). Individualized 90Y activities were based on dosimetry and were calculated to deliver cohort-defined RAD(1 to 17 Gy) to critical organs with three to six patients per cohort. The therapeutic dose of 90Y ibritumomab tiuxetan was followed by high-dose BEAM and autologous transplantation. Results Forty-four patients were treated. Thirty percent of patients had achieved less than a partial remission to their most recent therapy and would not have been eligible for autologous transplantation at most centers. The toxicity profile was similar to that associated with high-dose BEAM chemotherapy. Two dose-limiting toxicities occurred at the 17 Gy dose level, which made 15 Gy the recommended maximum-tolerated RAD. Although eight patients received at least twice the conventional dose of 0.4 mCi/kg, a weight-based strategy at 0.8 mCi/kg would have resulted in a wide range of RAD; nearly 25% of patient cases would have received 17 Gy or more, and many would have received less than 10 Gy. With a median follow-up of 33 months for all patients, the estimated 3-year progression-free and overall survivals were 43% and 60%, respectively. Conclusion Dose-escalated 90Y ibritumomab tiuxetan may be safely combined with high-dose BEAM with autologous transplantation and has the potential to be more effective than standard-dose radioimmunotherapy. Careful dosimetry is required to avoid toxicity and undertreatment.

Original languageEnglish (US)
Pages (from-to)1653-1659
Number of pages7
JournalJournal of Clinical Oncology
Volume27
Issue number10
DOIs
StatePublished - Apr 1 2009

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Winter, J. N., Inwards, D. J., Spies, S., Wiseman, G., Patton, D., Erwin, W., Rademaker, A. W., Weitner, B. B., Williams, S. F., Tallman, M. S., Micallef, I., Mehta, J., Singhal, S., Evens, A. M., Zimmer, M., Molina, A., White, C. A., & Gordon, L. I. (2009). Yttrium-90 ibritumomab tiuxetan doses calculated to deliver up to 15 Gy to critical organs may be safely combined with high-dose BEAM and autologous transplantation in relapsed or refractory B-cell non-hodgkin's lymphoma. Journal of Clinical Oncology, 27(10), 1653-1659. https://doi.org/10.1200/JCO.2008.19.2245