The Risk of Secondary Myelodysplastic Syndrome/Acute Leukemia and Second Malignancy Following Yttrium-90 Ibritumomab Tiuxetan: 10-Year Single-Institution Experience of 138 Consecutive Patients

Abstract 4876

Here we report one single centre experience with ⁹⁰Y Ibritumomab tiuxetan in order to investigate the incidence of treatment-related myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) or second malignancies after⁹⁰Y Ibritumomab tiuxetan.

From 2001 to 2012 a total of 138 patients received radioimmunotherapy (RIT) with ⁹⁰Y ibritumomab tiuxetan at European Institute of Oncology; 35 patients had Diffuse Large B Cell Lymphoma (DLBCL), 8 Mantle Cell Lymphoma (MCL), 61 Follicular Lymphoma (FL), 4 transformed FL, 27 Marginal Zone Lymphoma (MZL), 1 transformed MZL, 1 lymphoplasmacytoid lymphoma and 1 Burkitt. At time of treatment patients had a median age of 63 years (range, 21–85), 67 female and 71 male. They had received a median of 3 prior therapies (range, 1–11), including Rituximab, Radiotherapy and High Dose-Chemotherapy. ⁹⁰Y Ibritumomab Tiuxetan was administered at the activity of 14.8 MBq/kg in 98 patients, at 11.1 MBq/kg in 14 patients due to mild thrombocytopenia. Two patients had received ⁹⁰Y Ibritumomab Tiuxetan at further relapse (respectively 14.8 MBq/kg and 11.1 MBq/kg). In an experimental program - where PBSC transplantation was performed - an activity of 30 MBq/kg was delivered in 4 patients, 45 MBq/kg in 6 patients and 56 MBq/kg in 16 patients. After RIT 65 patients underwent further treatments due to relapse or progression, 7 patients underwent SC mobilization – with successful collection in 4 patients - and autologous transplantation.

With a median follow-up of 3 years (range 0–10.3), 2 patients developed MDS (they had received 30 and 45MBq/kg respectively) and 3 patients AML (2 patients had received 14.8 MBq/kg, 1 patient 56 MBq/kg), with an incidence of 3.6%. Events occurred at a median of 8 years (range, 6–10) after diagnosis of NHL and 3.8 years (range 2–5) after RIT. Multiple cytogenetic aberrations detected - principally involving chromosome 7 and 5 - time from diagnosis and previous treatments received, all support the correlation with previous CT as the result of cumulative damage rather than it being directly related to RIT. Finally 4 patients developed second malignancy with an incidence of 2.9%.

CONCLUSION: RIT does not appear to significantly increase the risk of second malignancies. These data suggest that the damage that leads to the development of second malignancy is probably cumulative and multifactorial. The incidences of MDS, AML or second tumors after ⁹⁰Y Ibritumomab tiuxetan are consistent with that expected if we consider the patients' treatment history. However a preliminary assessment of patient characteristics may help in identifying those most at risk: cytogenetic testing should be performed before RIT to verify pre-existing chromosomal abnormalities in heavily pretreated patients, in elderly patients and those previously exposed to alkylating agents or purine nucleoside analogs.