Low incidence of treatment-related myelodysplastic syndrome (tMDS) and acute myelogenous leukemia (tAML) in patients with non-Hodgkin's lymphoma (NHL) treated with ibritumomab tiuxetan

Abstract

6696 Introduction: 90Y Ibritumomab tiuxetan (Zevalin) radioimmunotherapy (RIT) was approved by the FDA in February 2002. RIT delivers high radiation dosage to tumors, and dose-limiting toxicity is hematological. Since tMDS/tAML has been associated with prior exposure to chemotherapy and radiation, we determined the incidence of tMDS/tAML in pts treated with ibritumomab tiuxetan from 4 registrational trials that have long-term follow-up. Results: In the 4 studies, 211 pts were treated with ibritumomab tiuxetan. These pts had received a median of 2 (range 1 - 9) prior treatments. With a median follow-up of 38 mos (range 1.2 - 75.5 mos), 7 pts (3.3%) have developed tMDS/tAML. Diagnosis of tMDS/tAML occurred 8 to 50 mos (median 18 mos) following therapy and 4.3 to 14 yrs (median 8 yrs) following the diagnosis of lymphoma. The annualized rates for the development of tMDS/tAML were 0.34% and 0.70% per yr from initial NHL diagnosis and from ibritumomab tiuxetan treatment date, respectively. This compares favorably to the published risk of tMDS/tAML in treated NHL pts of 1–1.5%/yr from 2 –10 yrs after initiation of therapy. Chromosome 5 and/or 7 abnormalities and/or deletions were detected in most pts, suggesting an association with prior alkylator-based therapy. In addition to the cases reported from the 4 registrational trials, there have been 5 cases of tMDS/tAML reported from 535 pts treated in an extended/compassionate use study (follow-up ranging from 0 - 36.5 mos). Two of these cases had documented abnormal baseline BM cytogenetic abnormalities prior to treatment with ibritumomab tiuxetan. Conclusions: Ongoing follow-up of pts from our registrational trials suggests that the annualized incidence of tMDS/tAML is consistent with that expected from this population of heavily treated NHL patients and does not appear to be increased following RIT with the ibritumomab tiuxetan therapeutic regimen. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration Biogen Idec, Inc. IDEL IDEC; IDEL IDEC IDEL