Rituximab with BEAM Conditioning Prior to Auto-HCT for DLBCL not Recommended

In a large registry analysis of patients with diffuse large B-cell lymphoma (DLBCL) undergoing auto-HCT, published in Cancer, the addition of rituximab (Rituxan) to the BEAM (BCNU, etoposide, cytarabine, melphalan) conditioning regimen had no impact on transplantation outcomes. 

Additionally, older age, absence of complete response (CR) pre auto-HCT, and early chemoimmunotherapy failure were associated with inferior survival. Given these findings, routine use of rituximab with BEAM conditioning prior to auto-HCT for DLBCL is not recommended.

“In the modern era, where rituximab is an integral part of DLBCL therapy, both in the up-front and relapsed setting, additional rituximab exposure with the conditioning chemotherapy does not appear to impact transplantation outcomes,” the authors wrote. 

Using the Center for International Blood and Marrow Transplant Research (CIBMTR) registry, researchers assessed 862 adult DLBCL patients undergoing auto-HCT between 2003 and 2017 using BEAM conditioning regimen. The cohort was divided into 2 groups, with 667 patients only using the BEAM conditioning regimen and the remaining 195 receiving rituximab in addition to BEAM (R-BEAM).

On multivariate analysis, no significant difference was observed in overall survival (OS; P = 0.83) or progression-free survival (PFS; P = 0.61) across the 2 cohorts. The 4-year OS was 61% (95% CI, 57%-65%) in the BEAM cohort compared to 58% (95% CI, 51%-65%) in the R-BEAM group (P = 0.77). Moreover, the 4-year PFS in the BEAM group was 47% (95% CI, 43%-51%) compared to 48% (95% CI, 41%-56%) in the R-BEAM group.

No significant association between the use of rituximab and risk of relapse (P = 0.15) or non-relapse mortality (P = 0.12) was seen. Institutional practice varies in regard to rituximab dose intensity and administration schedule in auto-HCT conditioning according to the researchers. Though it is plausible that higher rituximab doses intensity may improve auto-HCT outcomes, patients who received a higher dose of rituximab (>375 mg/m²) in this study had a similar relapse rate and survival compared with patients receiving the standard 375 mg/m² dose. 

“In the contemporary era, the benefit of combining an anti-CD20 monoclonal antibody with auto-HCT conditioning regiments is yet to be determined,” the authors wrote. “Prospective data incorporating rituximab with conditioning regimens are from nonrandomized studies or lack a BEAM-only comparative arm.”

Variables that were independently associated with lower OS included older age at auto-HCT (P < 0.001), absence of CR at auto-HCT (P < 0.001) and early chemoimmunotherapy failure (P < 0.001). Older age (P < 0.0002) and non-CR pre-HCT (P < 0.0001) were also associated with inferior PFS. Notably, progressive disease was the major cause of death in 68% and 55% of patients in the BEAM and R-BEAM cohorts, respectively. Infection was found to be a contributing secondary cause of death in 5% of BEAM deaths and 6% of R-BEAM deaths. 

Previously conducted multicenter and single institution retrospective studies have validated early rituximab-based regimen failure as a negative predictor for transplantation outcomes. Moreover, researchers indicated that post-transplantation maintenance is another attractive treatment modality in the ongoing efforts to reduce post-HCT relapse. 

“Due to lack of evidence, the (American Society for Blood and Marrow Transplantation), CIBMTR, and (European Society for Blood and Marrow Transplantation) joint consensus statement does not endorse post auto-HCT maintenance treatment in patients with DLBCL,” the authors wrote. “Results from the ongoing BMT CTN phase III randomized trial will address whether maintenance ibrutinib (Imbruvica) after auto-HCT can impact outcomes in nongerminal center DLBCL (NCT02443077).” 

Reference:

Jagadeesh D, Majhail NS, He Y, et al. Outcomes of Rituximab-BEAM Versus BEAM Conditioning Regimen in Patients With Diffuse Large B Cell Lymphoma Undergoing Autologous Transplantation. Cancer. doi:10.1002/cncr.32752.