Targeted Therapeutics Have a Role to Play in Stem Cell Transplants in Heavily Pretreated Non-Hodgkin’s Lymphoma

DUARTE, California-Radioimmunotherapy provides a unique opportunity to deliver systemic radiotherapy concurrently with immunotherapy, offering efficacy comparable with that of total body irradiation while reducing the toxicity. The ibritumomab tiuxetan (Zevalin) regimen is a radioimmunotherapeutic treatment that employs rituximab(Drug information on rituximab) (Rituxan) in addition to indium-111 radiolabeled ibritumomab tiuxetan (¹¹¹In-ibritumomab tiuxetan), and yttrium-90 radiolabeled ibritumomab tiuxetan (⁹⁰Y-ibritumomab tiuxetan). Because the therapeutic dose of radiation is targeted to a specific cell type (ie, CD20⁺ B cells), it reduces a patient's risk for toxicities associated with total body irradiation. A phase I/II trial tested this highdose regimen in combination with high-dose etoposide(Drug information on etoposide) and cyclophosphamide(Drug information on cyclophosphamide) (Cytoxan, Neosar), followed by autologous stem cell transplantation, in patients with poor-risk or relapsed B-cell non-Hodgkin's lymphoma (NHL).[1] Auayporn Nademanee, MD, of City of Hope National Medical Center in Duarte, California, presented data showing that the addition of a high-dose ibritumomab tiuxetan- rituximab regimen to high-dose etoposide and cyclophosphamide does not increase transplant-related toxicity and does not delay engraftment (ASH abstract 679).[1] Countdown to Transplant Twenty-six patients were enrolled and 18 patients were treated. Patient and disease characteristics are summarized in Table 1.[1] On day -21 before autologous stem cell transplantation, patients were treated with an intravenous infusion of 250 mg/m² rituximab to clear peripheral B cells and improve ibritumomab tiuxetan biodistribution, followed by dosimetry with 5 mCi ¹¹¹In-ibritumomab tiuxetan. One week later, patients received 40 to 100 mCi ⁹⁰Y-ibritumomab tiuxetan to obtain a target dose of no greater than 1,000 cGy to normal organs, combined with 5 mCi of ¹¹¹In-ibritumomab tiuxetan. High-dose etoposide (40 to 60 mg/ kg) was administered 4 days before transplant and high-dose cyclophosphamide (100 mg/kg), 2 days before transplant. Stem cells were reinfused when the radiation dose to the reinfused stem cells was estimated to be less than 5 cGy. The median delivered dose of ⁹⁰Y-ibritumomab tiuxetan was 74.9 mCi (range, 33.6 to 105 mCi). Treatment Well Tolerated The treatment was well tolerated. Mucositis, neutropenic fever, and rash were the most common acute toxicities. There were no transplant-related deaths. All patients achieved engraftment. The median time to reach an absolute neutrophil count above 500/μL was 10 days (range, 8 to 17 days) and the median time to reach a platelet count above 20,000/μL was 18 days (range, 12 to 123 days). These median times are similar to those reported for patients with high-risk, persistent, or relapsed NHL who received mobilized peripheral blood stem cell or autologous bone marrow transplants.[ 2] All seven patients with active disease at stem cell transplantation achieved complete remission. Seventeen of 18 treated patients were alive and in remission after a median follow- up of 8 months (range, 1 to 24 months). In addition, the 1-year estimated overall survival and diseasefree survival were both 92%. This preliminary study suggests that this novel treatment regimen may be effective in heavily pretreated patients with refractory NHL who are eligible to receive stem cell transplantation.