Radioimmunotherapy for B-Cell Non-Hodgkin Lymphomas
Radioimmunotherapy for B-Cell Non-Hodgkin Lymphomas
While the principal dose-limiting side effect of the approved agents is transient yet significant myelosuppression, patients recover blood counts effectively following RIT and in a predictable fashion. The delayed but nearly inevitable relapses of follicular lymphoma after RIT and the lower response rates of more aggressive lymphomas have led investigators to consider the potential value of repeat-dose RIT. Illidge et al reported on 16 patients with relapsed or transformed follicular lymphoma treated with weekly rituximab followed by 2 infusions of I rituximab. The cumulative total body exposure was 120 cGy. The OR rate was 94%, the CR rate was 50%, and the median time to progression was 20 months.
Shah et al reported on a retrospective analysis of patients who had received multiple infusions of Yibritumomab tiuxetan. Eighteen patients received 2 doses at a median of 16.6 months apart. Grade 3/4 neutropenia, thrombocytopenia, and OR rate were 35%, 41%, and 89% for the first RIT course, respectively, and 28%, 44%, and 77% for the second course. Similar safety and efficacy have been reported with I-tositumomab re-treatment.
More recently, Illidge et al reported early results of a phase II trial of planned tandem Y-ibritumomab tiuxetan infusions as sole therapy for patients with advanced follicular lymphoma. A total of 72 patients received Y-ibritumomab tiuxetan, and only 17% had the second infusion held due to failure of myelosuppression to resolve by 12 weeks. For all patients, the OR rate at the end of treatment was 96% (57% CR) compared with 97% and 64%, respectively, for those who received both planned infusions. Despite the repeat dosing schedule, myelosuppression was manageable, with only 8 patients requiring transfusion support.
One important consideration for a repeat dosing approach with Y-ibritumomab tiuxetan or I-tositumomab is that both antibodies are of murine origin, and patients previously exposed may form human antimurine antibodies (HAMA). Any patient being considered for repeat administration of either agent should be tested for the presence of HAMA prior to re-treatment since unrecognized presence of such antibodies could potentially trigger an anaphylactic reaction. In the Y-ibritumomab tiuxetan tandem infusion study by Illidge et al discussed above, the development of HAMA was 5.6%.
Repeat-dose RIT
While the principal dose-limiting side effect of the approved agents is transient yet significant myelosuppression, patients recover blood counts effectively following RIT and in a predictable fashion. The delayed but nearly inevitable relapses of follicular lymphoma after RIT and the lower response rates of more aggressive lymphomas have led investigators to consider the potential value of repeat-dose RIT. Illidge et al reported on 16 patients with relapsed or transformed follicular lymphoma treated with weekly rituximab followed by 2 infusions of I rituximab. The cumulative total body exposure was 120 cGy. The OR rate was 94%, the CR rate was 50%, and the median time to progression was 20 months.
Shah et al reported on a retrospective analysis of patients who had received multiple infusions of Yibritumomab tiuxetan. Eighteen patients received 2 doses at a median of 16.6 months apart. Grade 3/4 neutropenia, thrombocytopenia, and OR rate were 35%, 41%, and 89% for the first RIT course, respectively, and 28%, 44%, and 77% for the second course. Similar safety and efficacy have been reported with I-tositumomab re-treatment.
More recently, Illidge et al reported early results of a phase II trial of planned tandem Y-ibritumomab tiuxetan infusions as sole therapy for patients with advanced follicular lymphoma. A total of 72 patients received Y-ibritumomab tiuxetan, and only 17% had the second infusion held due to failure of myelosuppression to resolve by 12 weeks. For all patients, the OR rate at the end of treatment was 96% (57% CR) compared with 97% and 64%, respectively, for those who received both planned infusions. Despite the repeat dosing schedule, myelosuppression was manageable, with only 8 patients requiring transfusion support.
One important consideration for a repeat dosing approach with Y-ibritumomab tiuxetan or I-tositumomab is that both antibodies are of murine origin, and patients previously exposed may form human antimurine antibodies (HAMA). Any patient being considered for repeat administration of either agent should be tested for the presence of HAMA prior to re-treatment since unrecognized presence of such antibodies could potentially trigger an anaphylactic reaction. In the Y-ibritumomab tiuxetan tandem infusion study by Illidge et al discussed above, the development of HAMA was 5.6%.
