Brentuximab Vedotin Improves Survival in Relapsed/Refractory DLBCL

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The combination of brentuximab vedotin (Adcetris) and lenalidomide plus rituximab (Rituxan) demonstrated a statistically significant improvement in overall survival (OS) compared with lenalidomide and rituximab plus placebo in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), according to findings from the phase 3 ECHELON-3 trial (NCT04404283).¹

OS serves as the primary end point of the ECHELON-3 study. Improvements were also observed in the key secondary end points of progression-free survival (PFS) and overall response rate (ORR). Safety and tolerability findings of the combination were in line with previous reports.

The complete findings will be presented at an upcoming medical meeting.

“This is the third phase 3 study in a type of lymphoma to demonstrate an overall survival benefit for [the brentuximab vedotin] combination. 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,” said Roger Dansey, MD, chief development officer of oncology, Pfizer, in a press release.

“The results are particularly encouraging because the study evaluated heavily pre-treated patients, including some who received prior [chimeric antigen receptor (CAR) T-cell] therapy,” Dansey continued in the press release.

Brentuximab vedotin is currently FDA-approved for 7 indications across Hodgkin and non-Hodgkin lymphomas. Pfizer plans to share these positive findings from ECHELON-3 with the FDA in search of the eighth approved indication in this intent-to-treat population.

The phase 3 ECHELON-2 trial (NCT01777152) investigated brentuximab vedotin in combination with cyclophosphamide, doxorubicin, and prednisone for the treatment of patients with CD30-positive T-cell lymphoma. Findings presented at the 41st Annual Chemotherapy Foundation Symposium Innovative Cancer Therapy for Tomorrow conference in November 2023 showed an almost tripling in PFS compared with the standard of care.²

About the ECHELON-3 Study of Brentuximab Vedotin in DLBCL

ECHELON-3 is a randomized, double-blind, placebo-controlled, multicenter phase 3 study with an enrollment of 240 patients with relapsed or refractory DLBCL.³ Patients in the experimental arm are receiving brentuximab vedotin 1.2 mg/kg administered intravenously (IV) plus 375 mg/m² of rituximab as well as 20 mg of oral lenalidomide. Patients in the active comparator arm are receiving the same protocols of rituximab and lenalidomide plus placebo. Brentuximab vedotin and placebo are administered every 2 weeks. Rituximab is administered on cycle 1, day 1, and a further 1400-mg subcutaneous injection is allowed every 3 weeks from cycle 2, day 1, through the end of treatment.

The study’s primary end point is OS, and secondary end points include PFS, ORR, complete response rate, duration of response, incidence of adverse events, and OS in CD30-positive patients.

Patients must have relapsed or refractory disease following 2 or more lines of prior systemic therapy and be ineligible for stem cell transplant or CAR T-cell therapy. They must also have an ECOG performance status of 0 to 2.

Patients are ineligible for study participation if they have history of another malignancy within 2 years, active cerebral or meningeal disease, uncontrolled grade 3 or higher infection, have received previous treatment with brentuximab vedotin or lenalidomide, or are receiving immunosuppressive medications.

The study has an estimated completion date of April 30, 2027.

REFERENCES:

1. Pfizer announces positive overall survival in phase 3 trial of Adcetris regimen in patients with relapsed/refractory diffuse large B-cell lymphoma. News release. Pfizer. March 12, 2024. Accessed March 12, 2024. https://tinyurl.com/24n9we5u

2. Horwitz S. Updates in T-cell lymphoma. Presented at: 41st Annual Chemotherapy Foundation Symposium Innovation Cancer Therapy for Tomorrow conference; November 8-10, 2023; New York, NY.

3. Brentuximab vedotin plus lenalidomide and rituximab for the treatment of relapsed/refractory DLBCL (ECHELON-3). ClinicalTrials.gov. Updated February 20, 2024. Accessed March 12, 2024. https://clinicaltrials.gov/study/NCT04404283