Rituximab Conditioning Does Not Significantly Impact Outcomes for Patients With DLBCL Undergoing Transplant

By Cameron Kelsall, /alert Contributor
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The addition of rituximab to a traditional conditioning regimen prior to autologous hematopoietic cell transplant (auto-HCT) did not meaningfully impact transplant outcomes for patients with diffuse large B-cell lymphoma (DLBCL), according to results from a registry study published in Cancer.

Further, the researchers observed certain factors associated with worsened outcomes, including older age, lack of complete remission prior to transplant and early chemoimmunotherapy failure.

“The benefit of combining rituximab with auto-HCT conditioning regimens is not well defined, and no randomized clinical trials have explored the issue,” wrote Mehdi Hamadani, MD, professor of internal medicine at Medical College of Wisconsin, and colleagues. “Retrospective studies evaluating the integration of rituximab with conditioning regimens for auto-HCT in B-cell non-Hodgkin lymphoma have produced conflicting results.”

Hamadani and colleagues accessed retrospective data from the Center for International Blood and Marrow Transplant Research registry to evaluate outcomes among patients undergoing auto-HCT based on conditioning regimen.

The researchers identified 862 patients who received a transplant between 2003 and 2017. Patients were grouped based on conditioning regimen: carmustine, etoposide, cytarabine and melphalan (BEAM), alone (n = 667) or with rituximab (R-BEAM; n = 195).

All patients received first-line chemoimmunotherapy with rituximab and had chemosensitive disease, which the researchers defined as complete or partial remission prior transplant. Patients who did not achieve complete remission after first-line chemoimmunotherapy were considered in early chemoimmunotherapy failure, as were those who experienced relapse or progression within 1 year of diagnosis.

Overall survival (OS) served as the study’s primary outcome measure.

The researchers observed no overall difference in OS or progression-free survival (PFS) based on conditioning regimen. Patients who received BEAM conditioning had a 4-year median PFS of 47% (95% CI, 43-51), compared with 48% (95% CI, 41-56) for patients who received R-BEAM.

A multivariate analysis revealed factors associated with worsened PFS outcomes, including older age (≥50 years) at transplant (P < .0002) and lack of complete remission before auto-HCT (P < .0001).

The 4-year OS was 61% (95% CI, 57-65) for patients receiving BEAM conditioning and 58% (95% CI, 51-65) for patients receiving R-BEAM conditioning.

Factors associated with inferior OS included older age at transplant, lack of complete remission and early chemoimmunotherapy failure (P < .001 for all).

Rituximab receipt was not associated with significant differences in 1-year nonrelapse mortality (BEAM vs. R-BEAM, 5% vs. 6%) or 4-year cumulative incidence of relapse or progression (44% vs. 41%). Multivariate analyses showed that patients aged 65 years and older had a significantly higher risk for nonrelapse mortality (P < .01) and patients in partial remission prior to transplant had a higher risk for relapse/progression (P < .0001).

In addition, rituximab receipt did not significantly increase the risk for any infection (viral, bacterial or fungal) within the first 100 days following auto-HCT.

Disease relapse was the leading cause of death in both groups (BEAM vs. R-BEAM, 68% vs. 55%).

“In the modern era, where rituximab is an integral part of DLBCL therapy, both in the upfront and relapsed setting, additional rituximab exposure with the conditioning chemotherapy does not appear to impact transplantation outcomes,” the researchers concluded. “Based on our results, routine use of rituximab with BEAM conditioning prior to auto-HCT for DLBCL is not recommended.”

 

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