RIT combines the effects of radiotherapy with immunologic targeting of cell-type-specific monoclonal antibodies for treating lymphoma. Our findings suggest that incorporating ibritumomab tiuxetan into treatment with BuCyE compared with BuCyE alone for ASCT is feasible and may provide additional benefits for patients with relapsed or refractory B-cell NHL.
Our EFS findings are consistent with results of previous studies, suggesting a potential benefit of ibritumomab tiuxetan administration for patients receiving BuCyE followed by ASCT. For example, several studies comparing Z-BEAM with BEAM alone have reported improved efficacy for patients with B-cell NHL. Krishnan et al. demonstrated favorable outcomes in 65 patients with aggressive NHL, with 2-year EFS rates of 72% and 67% in the Z-BuCyE and BuCyE groups, respectively [12
]. A randomized phase II study reported a trend toward improved EFS at 2 years in the Z-BEAM group (N=22) of 59% versus 37% for the BEAM group (N=21) [13
]. In this study, improved EFS in the Z-BuCyE group is likely attributable to the prolonged CR duration after Z-BuCyE conditioning compared with that after BuCyE conditioning (15.9 months versus 7.7 months). As an additive effect of RIT in ASCT, RIT agents such as ibritumomab tiuxetan appear to have advantages based on the emission of β-particles, which can penetrate several millimeters [21
]. Hence, RIT with ibritumomab tiuxetan makes it possible to deliver a therapeutic dose of radiation not only to nearby lymphoma cells, but also to neighboring cells that are farther from the tumor surface. This feature may prolong the duration of the response [23
RIT alone is associated with hematologic toxicities. However, hematologic toxicities observed following RIT can be overcome using SC infusion [25
]. In the current study, toxicity profiles of the patients in the Z-BuCyE group were comparable with those of the BuCyE group patients, although 1 patient in the Z-BuCyE group died from VOD. Ibritumomab tiuxetan appears to be safely incorporated into myeloablative regimens, as life-threatening hematologic toxicities associated with RIT and HDC were rescued with ASCT, which was demonstrated by only 1 patient who experienced septicemia. This favorable toxicity profile is encouraging, considering that most patients enrolled in this cohort were middle-aged or elderly.
Till the time of manuscript preparation, no patients in this cohort had developed secondary malignancy. Although there are concerns regarding the development of secondary malignancies following RIT combined with ASCT, secondary malignancies with high-dose Z-BEAM have been observed in only 7% of patients, which is similar to the rate observed with HDC alone [27
]. Moreover, adverse events were similar to those seen with BEAM alone [8
]. Data from a larger number of patients with a longer duration of follow-up are required to properly evaluate the probability of developing secondary malignancies.
Survival outcomes for the cohort appear to be numerically inferior compared with our previous results [16
]. Although the CR rates of 78.9% and 73.7% in the Z-BuCyE and BuCyE groups after ASCT were relatively high, EFS and OS data in this study were not promising. This may be due, at least in part, to adverse patient characteristics such as multiple extranodal involvement, as well as extensive previous treatment (chemotherapy and/or radiotherapy) () [29
Nevertheless, because of the similarities between the Z-BuCyE and BuCyE groups in terms of disease-related characteristics affecting prognosis such as histology, disease status at the time of salvage, and the number of prior regimens, our results may provide further information about the role of ibritumomab tiuxetan in conditioning regimens in combination with ASCT.
This study has some limitations. The study was retrospective in nature, included a small number of patients with a relatively short follow-up period, and involved a selected group of patients with relatively poor clinical features. Nevertheless, the patient cohort was derived from patients treated with a uniform treatment protocol in a single center.
In conclusion, our findings suggest that the use of ibritumomab tiuxetan in combination with BuCyE may increase treatment efficacy as well as reduce treatment toxicity and yield an engraftment profile similar to that of BuCyE alone. These observations should be further examined in a randomized study to define the role of RIT for treating lymphoma patients.