Brentuximab Vedotin Combination Shows 37% Reduction in Risk of Death in Relapsed or Refractory DLBCL

The addition of brentuximab vedotin (BV) to lenalidomide plus rituximab (R2) resulted in a statistically significant overall survival (OS) advantage over R2 alone in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).¹

The median OS shown was 13.8 months (95% CI, 10.3-18.8) in patients treated with BV+R2 versus 8.5 months (95% CI, 5.4-11.7) in those treated with R2 alone, resulting in a 37% reduction in the risk of death (hazard ratio [HR], 0.629; 95% CI, 0.445-0.891; P=.0085), according to published results from the phase III ECHELON-3 study (NCT04404283). The OS benefit was consistent across the high-risk subgroups assessed in the study.

“The overall survival benefit of BV+R2 is clearly clinically meaningful and somewhat surprising given the modest PFS [progression-free survival] benefit. This is particularly true in this older patient population,” Craig A. Portell, MD, a study co-investigator and clinical faculty member, Division of Hematology/Oncology at the University of Virginia told Blood Cancers Today.

In terms of PFS, BV+R2 showed a median of 4.2 months (95% CI, 2.9-7.1) compared with a median of 2.6 months (95% CI, 1.4-3.1) with R2, achieving a 47% reduction in the risk of disease progression or death (HR, 0.527; 95% CI, 0.380-0.729; P<.0001).

The objective response rate observed with BV+R2 was 64.3% (95% CI, 54.7-73.1) versus 41.5% (95% CI, 32.5-51.0) in the R2-only arm (P=.0006). Complete responses were achieved in 40.2% of the BV+R2 arm compared with 18.6% of the R2 arm. The median duration of response was 8.3 months (95% CI, 4.2-15.3) with BV+R2 versus 3 months (95% CI, 2.8-5.4) with R2 alone.

Grade ≥3 treatment-emergent adverse events (TEAEs) were observed in 88% of patients in the BV+R2 arm compared with 77% of patients in the R2-alone arm, and serious TEAEs occurred in 60% versus 50%, respectively. Grade 5 TEAES occurred in 2% of the BV+R2 arm versus 8% of the R2 arm.

Portell stated that “while cytopenias were common, neutropenic fever was not, and there were no new safety signals that were seen.” In the BV+R2 arm versus the R2-only arm, investigators reported the most common TEAEs as neutropenia in 46% versus 32%, anemia in 29% versus 27%, and diarrhea in 31% versus 23%, respectively. Thirty-one percent of the BV+R2 arm had peripheral neuropathy compared with 24% of the R2 arm.

Efficacy and safety data from ECHECLON-3 come from a cohort of 230 patents with relapsed or refractory DLBCL, 112 of whom received BV+R2 and 118 of whom received R2 alone. All patients enrolled received at least one dose of study treatment, and the median duration of treatment was 3.6 months in the BV+R2 arm and 2.0 months in the R2-only arm. All patients had a median of three (range, 2–8) prior lines of therapy including prior chimeric antigen receptor (CAR) T-cell therapy.

Based on the findings at a median follow-up of 16.4 months (range, 0.1-31.5 months), investigators have deemed BV+R2 a novel therapeutic option for heavily pretreated, relapsed or refractory DLBCL. According to ECHELON-3 investigators, this is important, considering that patients with relapsed or refractory DLBCL who experience relapse after transplant or who are ineligible for transplant or CAR T-cell therapy have a poor prognosis.²

“I think we need to understand why BV added such a benefit in OS. Even with the target of BV, CD30 was not expressed. Hopefully, some correlative work with samples from the study will help with this,” said Portell.

References

1. Bartlett N, Hahn U, Kim W, et al. Brentuximab vedotin combination for relapsed diffuse large B-cell lymphoma. J Clin Oncol. Published January 7, 2025. doi:1200/JCO-24-02242
2. Bartlett N, Yasenchak C, Ashraf K, et al. Brentuximab vedotin in combination with lenalidomide and rituximab in patients with relapsed/refractory diffuse large B-cell lymphoma: safety and efficacy results from the safety run-in period of the phase 3 ECHELON-3 study. J Clin Oncol. 2022;40(16):suppl 7559. doi:1200/JCO.2022.40.16_suppl.755