Brentuximab Vedotin Combo Significantly Improves Survival in R/R DLBCL

In the double-blind, multicenter ECHELON-3 trial (NCT04404283), 230 patients from North America, Europe, and the Asia-Pacific region were randomly assigned to receive brentuximab vedotin at 1.2 mg/kg intravenously every 3 weeks or matched placebo plus lenalidomide and rituximab.

Combining brentuximab vedotin (Adcetris) with lenalidomide (Revlimid) and rituximab (Rituxan) elicited a clinically meaningful and statistically significant improvement in overall survival (OS) compared with lenalidomide plus rituximab and placebo among patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to a press release on findings from the phase 3 ECHELON-3 trial (NCT04404283).¹

Data also highlighted a progression-free survival (PFS) and overall response rate (ORR) benefit with the brentuximab vedotin combination. The safety and tolerability data in the ECHELON-3 trial were comparable with prior reports of brentuximab vedotin in the management of relapsed/refractory DLBCL.

Investigators will submit their final findings for presentation at a future medical conference, and will also share the results with the FDA to support regulatory filling.

“This is the third phase 3 study in a type of lymphoma to demonstrate an [OS] benefit for a [brentuximab vedotin] combination,” Roger Dansey, MD, chief development officer of Oncology at Pfizer, said in the press release.¹ “Based on the strong results from ECHELON-3, we’re excited that [brentuximab vedotin] could address an area of high unmet need in patients with relapsed or refractory DLBCL irrespective of CD30 expression. The results are particularly encouraging because the study evaluated patients who were heavily pre-treated, including some who received prior CAR T-cell therapy.”

In the double-blind, multicenter ECHELON-3 trial, 230 patients from North America, Europe, and the Asia-Pacific region were randomly assigned to receive brentuximab vedotin at 1.2 mg/kg intravenously every 3 weeks or matched placebo plus lenalidomide and rituximab.² Investigators administered rituximab at 375 mg/m² intravenously on day 1 of cycle 1, with subcutaneous doses at 1400 mg permitted every 3 weeks from day 1 of cycle 2 onward. Additionally, patients received lenalidomide 20 mg orally once a day.

The trial’s primary end point was OS. Secondary end points included PFS, ORR, complete response rate, duration of response, and adverse effects.

Patients 18 years and older with histologically confirmed relapsed/refractory DLBCL and at least 2 prior lines of systemic therapy who are ineligible to receive hematopoietic stem cell transplantation or CAR T-cell therapy were able to enroll on the trial. Additional eligibility criteria included having available tumor tissue for central pathology lab review, an ECOG performance status of 0 to 2, and bidimensional measurable disease of 1.5 cm or larger based on radiologist assessment within 28 days of study entry.

Those with another malignancy within 2 years of beginning study treatment, a history of progressive multifocal leukoencephalopathy, or any uncontrolled grade 3 or higher viral, bacterial, or fungal infection within 2 weeks before beginning treatment were ineligible for enrollment. Patients were also unsuitable for enrollment if they had prior treatment with brentuximab vedotin or lenalidomide; current treatment with immunosuppressive medications, systemic anti-neoplastic agents, or investigational therapies; or congestive class III or IV heart failure based on New York Heart Association classification.

The European Commission previously approved brentuximab vedotin in combination with doxorubicin (Adriamycin), vinblastine and dacarbazine for adult patients with previously untreated CD30-positive stage III Hodgkin lymphoma in October 2023.³ Supporting data for this approval came from the phase 3 ECHELON-1 trial (NCT01712490), in which the brentuximab vedotin combination met the primary end point of PFS and elicited a statistically significant improvement in OS compared with doxorubicin plus bleomycin, vinblastine, and dacarbazine.

“This approval is an exciting advancement in care, allowing even more [patients with] lymphoma to access the proven efficacy, consistent safety, and tolerability that [brentuximab vedotin] is known to deliver,” lead study investigator John Radford, MD, FMedSci, a professor at University of Manchester and the Christie NHS Foundation, said in a press release at the time of the approval.³

References

1. Pfizer announces positive overall survival in phase 3 trial of ADCETRIS® regimen in patients with relapsed/​refractory diffuse large B-cell lymphoma (DLBCL). News release. Pfizer Inc. March 12, 2024. Accessed March 12, 2024. https://tinyurl.com/2h8u9pb5
2. Brentuximab vedotin plus lenalidomide and rituximab for the treatment of relapsed/​refractory DLBCL (ECHELON-3). ClinicalTrials.gov. Accessed March 12, 2024. https://tinyurl.com/2fajp4bw
3. European Commission approves ADCETRIS® (brentuximab vedotin) for the treatment of adult patients with previously untreated CD30+ stage III Hodgkin lymphoma in combination with AVD. News release. Takeda. October 18, 2023. Accessed March 12, 2024. https://shorturl.at/hAPU9