Phase III randomized study of rituximab/carmustine, etoposide, cytarabine, and melphalan (BEAM) compared with iodine-131 tositumomab/BEAM with autologous hematopoietic cell transplantation for relapsed diffuse large B-cell lymphoma: results from the BMT CTN 0401 trial

Abstract

Purpose: This clinical trial evaluated standard-dose radioimmunotherapy with a chemotherapy-based transplantation regimen followed by autologous hematopoietic cell transplantation versus rituximab with the same regimen in patients with relapsed diffuse large B-cell lymphoma (DLBCL).

Patients and methods: Patients with chemotherapy-sensitive persistent or relapsed DLBCL were randomly assigned to receive iodine-131 tositumomab (dosimetric dose of 5 mCi on day -19 and therapeutic dose of 0.75 Gy on day -12), carmustine 300 mg/m(2) (day -6), etoposide 100 mg/m(2) twice daily (days -5 to -2), cytarabine 100 mg/m(2) twice daily (days -5 to -2), and melphalan 140 mg/m(2) (day -1; B-BEAM) or rituximab 375 mg/m(2) on days -19 and -12 and the same chemotherapy regimen (R-BEAM).

Results: Two hundred twenty-four patients were enrolled, with 113 patients randomly assigned to R-BEAM and 111 patients assigned to B-BEAM. Two-year progression-free survival (PFS) rates, the primary end point, were 48.6% (95% CI, 38.6% to 57.8%) for R-BEAM and 47.9% (95% CI, 38.2% to 57%; P = .94) for B-BEAM, and the 2-year overall survival (OS) rates were 65.6% (95% CI, 55.3% to 74.1%) for R-BEAM and 61% (95% CI, 50.9% to 69.9%; P = .38) for B-BEAM. The 100-day treatment-related mortality rates were 4.1% (95% CI, 0.2% to 8.0%) for R-BEAM and 4.9% (95% CI, 0.8% to 9.0%; P = .97) for B-BEAM. The maximum mucositis score was higher in the B-BEAM arm (0.72) compared with the R-BEAM arm (0.31; P < .001).

Conclusion: The B-BEAM and R-BEAM regimens produced similar 2-year PFS and OS rates for patients with chemotherapy-sensitive relapsed DLBCL. No differences in toxicities other than mucositis were noted.

Trial registration: ClinicalTrials.gov NCT00329030.

Conflict of interest statement

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

Figures

Fig 1.

CONSORT diagram outlining the number of patients at each step of the trial. B-BEAM, iodine-131 tositumomab plus carmustine, etoposide, cytarabine, and melphalan; R-BEAM, rituximab plus carmustine, etoposide, cytarabine, and melphalan.

Fig 2.

(A) Progression-free survival (PFS) according to random assignment groups. (B) Overall survival according to random assignment groups. (C) PFS of patients in second complete response according to random assignment groups. (D) PFS of patients with chemotherapy-sensitive relapse according to random assignment groups. B-BEAM, iodine-131 tositumomab plus carmustine, etoposide, cytarabine, and melphalan; R-BEAM, rituximab plus carmustine, etoposide, cytarabine, and melphalan.

Fig 3.

(A) Cumulative incidence of disease progression or relapse according to random assignment groups. (B) Cumulative incidence of transplantation-related mortality according to random assignment groups. B-BEAM, iodine-131 tositumomab plus carmustine, etoposide, cytarabine, and melphalan; R-BEAM, rituximab plus carmustine, etoposide, cytarabine, and melphalan.