Randomized Phase III Trial of 131 iodine-Tositumomab (Bexxar)/Carmustine, Etoposide, Cytarabine, Melphalan (BEAM) Vs. Rituximab/BEAM and Autologous Stem Cell Transplantation for Relapsed Diffuse Large B-Cell Lymphoma (DLBCL): No Difference in Progression-Free (PFS) or Overall Survival (OS)

Abstract Abstract 661 Objective: To compare 131Iodine-Tositumomab/BEAM to Rituximab/BEAM as the conditioning regimen followed by autologous stem cell transplantation for patients with relapsed chemotherapy sensitive DLBCL. Patients and Methods: The Blood and Marrow Transplant Clinical Trials Network (BMT CTN 0401) study sponsored by the National Heart, Lung, and Blood Institute and the National Cancer Institute enrolled 224 patients between 1/06 and 7/09. Eligible patients were age 18–80 years, had a Karnofsky performance score > 70%, persistent or recurrent DLBCL, chemotherapy sensitive disease, and had received 1–3 prior chemotherapy regimens. Patients with transformed DLBCL were excluded. Patients were randomized to receive 131Iodine Tositumomab (dosimetric dose of 5 mCi on day −19 and therapeutic dose of 75 cGy on day −12), carmustine 300 mg/m2 (day −6), etoposide 100 mg/m2 twice daily × 4 (days −5 to −2), cytarabine 100 mg/m2 twice daily × 4 (days −5 to −2), and melphalan 140 mg/m2 (day −1) (Bexxar/BEAM, n=111) vs. rituximab 375 mg/m2 on days −19 and −12 with the BEAM regimen (R/BEAM, n=113). All drugs were given intravenously. The median age at the time of transplant was 56.8 years in the Bexxar/BEAM and 58.8 years in the R/BEAM arm. All 224 patients were included in the intent to treat analysis for the primary endpoint of 2-year PFS. Twelve patients were not transplanted and two patients were ineligible based upon incorrect pathologic subtype and therefore were not included in further analyses Results: The median follow-up of the patients was 25.5 months (mo) (range 13.8– 47.0) in the Bexxar/ BEAM and 24.7 mos (range 4.7 – 58.6) in the R/BEAM arms, respectively. The primary end point of 2-year PFS was 47.9% (95% CI: 38.2%, 57.0%) for Bexxar/BEAM and 48.6% (95% CI: 38.6%, 57.8%) for R/BEAM (p= 0.94). The 2-year OS of all randomized patients was 61.0% (95% CI: 50.9%, 69.6%) for Bexxar/BEAM and 65.6% (95% CI: 55.3%, 74.1%) for R/BEAM (p= 0.38). Patients in complete remission after salvage chemotherapy (CR2) had an improved 2-yr OS compared to patients with primary induction failure (PIF) or chemosensitive relapse (p= 0.005). However, there were no differences in any group by treatment arm. 2-yr OS for CR2 patients with Bexxar/BEAM was 76.9% (95% CI: 62.9%, 86.1%) compared to 79.9% (95% CI: 64.7%, 89.1%) with R/BEAM (p= 0.61). The most common cause of failure was progression/relapse of the lymphoma with a cumulative incidence of relapse/progression at 2 yrs post transplant of 45.0% (95% CI: 35.2%, 54.8%) in the Bexxar/BEAM arm and 48.1% (95% CI: 38.1%, 58.1%) in the R/BEAM arm (p= 0.69). The treatment related mortality was 4.9% (95% CI: 0.8%, 9.0%) in the Bexxar/BEAM and 4.1% (95% CI: 0.2%, 8.0%) in the R/BEAM arms at 2 years post transplant (p= 0.97). Engraftment was similar with neutrophils to > 500/ul in 96.1% (95% CI: 92.2%, 100%) of Bexxar/BEAM and 93.5% (95% CI: 88.6%, 98.4%) of R/BEAM patients by day +28 (p= 0.40). Platelet recovery to > 20,000/ul with no transfusion by day +100 was present in 84.5% (95% CI: 77.4%, 91.6%) of the Bexxar/BEAM and 81.3% (95% CI: 73.9%, 88.7%) of the R/BEAM patients (p= 0.58). The median maximum mucositis score (by OMAS scale) was higher in the Bexxar/BEAM patients at 0.72 compared to 0.31 in the R/BEAM patients (p < 0.0001). One case of myelodysplastic syndrome (MDS) was reported in each arm of the trial and one additional case of acute myelogenous leukemia (AML) was reported in the R/BEAM arm. By exploratory analyses, immune reconstitution as measured by levels of quantitative immunoglobulins and B and T-lymphocyte subsets was not different between the two randomized arms at baseline, day +100, day +365, or day +730. Conclusions: The Bexxar/BEAM and the R/BEAM regimens produced similar 2-yr PFS and OS for patients with chemotherapy sensitive relapsed DLBCL. No differences in engraftment or other toxicities were apparent other than an increase in mucositis with the Bexxar/BEAM regimen. No significant difference in the risk of MDS or AML could be detected with the current follow up. Disclosures: Vose: Genentech: Research Funding; Pharmacyclics: Research Funding; SBio: Research Funding; Exelixis: Research Funding; BMS: Research Funding; Celgene: Research Funding; Millenium: Research Funding; GSK: Research Funding. Off Label Use: 131 Iodine Tositumomab combined with BEAM chemotherapy as a transplant preparative regimen for diffuse large B-cell lymphoma is an off label use. Burns:Novartis: Research Funding. Press:Roche/Genentech: Consultancy, Honoraria; Spectrum: Consultancy, Honoraria. Fenske:Seattle Genetics: Consultancy, Honoraria; Spectrum Pharmaceuticals: Consultancy, Honoraria; Millennium (Takeda) Pharmaceuticals: Research Funding.