Brentuximab Vedotin Plus Lenalidomide and Rituximab Generates OS Benefit in Previously Treated DLBCL

Roger Dansey, MD

Treatment with the antibody-drug conjugate (ADC) brentuximab vedotin (Adcetris) in combination with lenalidomide (Lenvima) and rituximab (Rituxan) led to a statistically significant and clinically meaningful improvement in overall survival (OS) compared with lenalidomide and rituximab plus placebo in patients with relapsed/refractory diffuse large B-cell lymphoma (DLBCL), according to data from the phase 3 ECHELON-3 trial (NCT04404283) shared in a press release from Pfizer.¹

Findings from the ongoing, randomized, double-blind, multicenter study demonstrated positive outcomes in relation to key secondary end points, including progression-free survival (PFS) and overall response rate (ORR).

Full data will be submitted for presentation at an upcoming medical meeting, and Pfizer plans to share the updated ECHELON-3 data with the FDA to support a regulatory filing for the agent in the United States.

“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, stated in the press release. “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 heavily pretreated patients, including some who received prior [CAR T-cell] therapy.”

DLBCL currently stands as one of the most prevalent forms of lymphoma, characterized by rapid growth and aggressive behavior within the bloodstream. Approximately 40% of patients with DLBCL either progress on initial treatment or experience relapse in disease following first-line therapy. However, brentuximab vedotin represents a standard treatment option for patients with certain lymphomas.

The ADC is made up of a CD30-directed monoclonal antibody attached by a protease-cleavable linker to the microtubule disrupting agent monomethyl auristatin E (MMAE); the ADC then employs a linker system that is designed to be stable in the bloodstream as it releases MMAE upon internalization into CD30-positive tumor cells.

To date, 230 eligible patients with relapsed/refractory DLBCL have been randomly assigned to the trial across North America, Europe, and Asia-Pacific. Patients are eligible for study treatment if they are relapsed/refractory to 2 or more prior lines of systemic therapy; ineligible for hematopoietic stem cell transplantation or CAR T-cell therapy; have submitted tumor tissue from their most recent DLBCL biopsy; have an ECOG performance status of 0 to 2; and have demonstrated fluorodeoxyglucose-avid disease by PET with bidimensional measurable disease of at least 1.5 cm by CT within 28 days of day 1 of the study.²

The primary end point of the study is OS in the intent-to-treat population. Key secondary end points include PFS and ORR as assessed by investigators, and other end points include complete response rate, duration of response, safety, and tolerability.

The safety profile of the treatment combination was consistent with what has been previously presented for patients with relapsed/refractory DLBCL treated with brentuximab vedotin in clinical trials.¹

To date, brentuximab vedotin has been approved for 7 indications in the United States:

• Brentuximab vedotin in combination with chemotherapy as a frontline option for adult patients with stage III or IV classical Hodgkin lymphoma
• Brentuximab vedotin in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide in pediatric patients 2 years of age and older with previously untreated, high-risk classical Hodgkin lymphoma
• Brentuximab vedotin as a consolidation therapy following autologous stem cell transplantation in patients with classical Hodgkin lymphoma at risk of relapse or progression
• Brentuximab vedotin following failure of autologous hematopoietic stem cell transplant (auto-HSCT) or after progression on at least 2 prior multi-agent chemotherapy regimens in patients with classical Hodgkin lymphoma who are not auto-HSCT candidates
• Brentuximab vedotin for use in combination with chemotherapy for the frontline treatment of adult patients with CD30-expressing peripheral T-cell lymphoma
• Brentuximab vedotin in adult patients with systemic anaplastic large cell lymphoma (ALCL) after progression on at least 1 prior multi-agent chemotherapy regimen
• Brentuximab vedotin as a treatment for patients with primary cutaneous (ALCL) who have received prior systemic therapy

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. March 12, 2024. Accessed March 12, 2024. https://www.pfizer.com/news/press-release/press-release-detail/pfizer-announces-positive-overall-survival-phase-3-trial
2. 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