Zevalin, Chemotherapy, ASCT Combination Produces High Overall Survival In Patients With Relapsed Non-Hodgkin's Lymphoma
Results of Cell Therapeutics' phase II clinical study demonstrate that the addition of radioimmunotherapy (RIT) to high-dose chemotherapy (HDC) followed by autologous stem-cell transplantation (ASCT) produced a high rate (70 percent) 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.
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 percent) 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) percent. Importantly the 2-year overall and progression-free survival estimates were approximately 89 percent and 70 percent, 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 at CTI.
he 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. Median age of the patients treated was 59.6 years (range 19.8 to 78.9 years). Lymphoma histologies included diffuse B cell (n=20), mantle cell (n=13), follicular (n=4) and transformed (n=4). Median tumor bulk prior to treatment was 3.1cm; median number of prior therapies was 2 with range 1-6. Thirty-five of the 41 patients were alive at the time of analysis; 27 were in remission. With a median follow-up of 18.4 months (range 5.5 to 53.3 months), the Kaplan-Meier estimated 2-year OS and PFS were 88.9 percent and 69.8 percent, respectively. 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 percent. The authors concluded: "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".