Yttrium-90 ibritumomab tiuxetan (Zevalin) has been shown to be an effective and well-tolerated therapy for patients with relapsed B-cell non-Hodgkin’s lymphoma (NHL), with a response rate significantly higher than that seen with rituximab(Drug information on rituximab) (Rituxan). The predominant toxicity of ibritumomab tiuxetan has been reversible myelosuppression; five cases of myelodysplastic syndrome have been reported in a total of 349 patients who have received ibritumomab tiuxetan. Due to the bone marrow suppression seen with ibritumomab tiuxetan, concern has been expressed about the tolerability of further therapy at the time of progression after ibritumomab tiuxetan therapy.The goal of this retrospective analysis was to evaluate what treatments were administered to patients who relapsed after ibritumomab tiuxetan therapy and to assess how well these therapies were tolerated. A total of 54 patients were treated at the Mayo Clinic on three separate protocols that utilized ibritumomab tiuxetan at 0.4 mCi/kg. The median number of therapies prior to ibritumomab tiuxetan was 2 (range: 1-7). Two patients developed myelodysplastic syndrome and 35 patients have progressed after ibritumomab tiuxetan therapy. One patient died before subsequent therapy was started, while 34 patients received other chemotherapy regimens. The median number of subsequent therapies was 3 (range: 1-7). The number of patients receiving subsequent therapies after ibritumomab tiuxetan is shown in the table below:
Six patients were treated with an autologous stem cell transplant. Five had peripheral blood stem cells successfully collected after ibritumomab tiuxetan therapy utilizing growth factor mobilization. One patient required a bone marrow harvest due to inadequate peripheral blood stem cell mobilization. One additional patient had an allogeneic transplant. All patients regained adequate blood counts after transplantation.
Thirteen of the 34 patients required growth factor support with subsequent chemotherapy (other than the conditioning regimen for stem cell transplantation). However, only 1 patient had a 25% dose reduction at the start of the subsequent treatment regimen due to low counts after previous ibritumomab tiuxetan. Aside from those hospitalized at the time of transplantation, 10 patients were hospitalized at some point due to neutropenic fever and/or thrombocytopenia. One patient died of infectious complications after the third chemotherapy regimen given after ibritumomab tiuxetan.
CONCLUSION: We conclude that chemotherapy or autologous stem cell harvest and transplantation after prior therapy with ibritumomab tiuxetan is feasible and reasonably well tolerated. Patients may require growth factor support or possibly dose modification with subsequent therapies. It is not known, however, if the tolerability of subsequent chemotherapy after ibritumomab tiuxetan is different than that seen in similar patients treated with other salvage chemotherapy regimens.