The results of a phase II clinical study by Cell Therapeutics, Inc. (CTI) showed that the addition of radioimmunotherapy (RIT) to high-dose chemotherapy (HDC) followed by autologous stem-cell transplantation (ASCT) produced a high rate of progression-free survival at two years without a significant increase in the toxicity of the HDC regimen underscoring the potential role for RIT in ASCT. The results were published in the Journal of Clinical Oncology.
Total-body irradiation (TBI) has previously been shown to significantly increase progression-free survival when added to HDC followed by ASCT as compared to HDC alone. However, TBI has long term complications and not all patients are eligible to receive TBI as part of their preparative regimen. Radioimmunotherapy with Zevalin (Ibritumomab Tiuxetan), approved for follicular, low grade NHL which relapsed following 1st line rituximab based therapy, allows high doses of lymphoma-targeted radiation with lower doses to normal tissues.
The study, conducted at the City of Hope Comprehensive Cancer Center, used a single dose of Zevalin in patients undergoing ASCT following HDC with the BEAM regimen (carmustine, cytarabine, etoposide, and melphalan). Thirty-seven of the 41 patients had failed prior rituximab therapy. Seven of the ten patients transplanted in partial remission (70 per cent) converted to complete remissions following the Zevalin-based regimen. The addition of Zevalin to the BEAM regimen did not appear to add to the toxicity of HDC; the day 100 mortality rate was zero (0) per cent. Importantly the 2-year overall and progression-free survival estimates were approximately 89 per cent and 70 per cent, respectively.
"The promise of utilizing targeted radioimmunotherapy together with high-dose chemotherapy prior to autologous stem-cell transplant is an exciting new potential application of Zevalin. We expect to explore this as an additional registration direction for Zevalin," noted Jack W. Singer, M.D. chief medical officer, CTI.
The trial evaluated the safety and efficacy of combining a standard dose of Zevalin (14.8 MBq/kg [0.4mCi/kg]) followed by high-dose BEAM and ASCT in patients with non-Hodgkin's lymphoma who were considered ineligible for total-body irradiation because of older age or prior radiotherapy. Primary endpoints of the study were overall (OS) and progression-free survival (PFS). Secondary endpoints included safety and long-term complications. Sixty patients were enrolled with 41 patients receiving full protocol of imaging and therapy. The primary toxicities observed included grade 3 or 4 mucositis in 21 patients, grade 3 hypoxia in eight patients, and grade 3 pneumonitis, which responded to corticosteroids, in 3 patients. Transplantation-related mortality at 100 days was 0 per cent. Combining 90Y ibritumomab tiuxetan with high dose BEAM before ASCT is feasible with no evidence of increase toxicity. The high rates of PFS, especially in patients with DBCL are also encouraging, the study said.
Zevalin, (Ibritumomab Tiuxetan), is a form of cancer therapy called radioimmunotherapy and is indicated for the treatment of patients with relapsed or refractory low-grade or follicular B-cell NHL, including patients with Rituximab-refractory NHL. It was approved by the FDA in February of 2002 as the first radioimmunotherapeutic agent for the treatment of NHL.
Headquartered in Seattle, CTI is a biopharmaceutical company committed to developing an integrated portfolio of oncology products aimed at making cancer more treatable.