FDA Approves Pfizer’s Adcetris for Relapsed or Refractory Large B-Cell Lymphoma

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The FDA has approved Pfizer’s supplemental Biologics License Application (sBLA) for Adcetris (brentuximab vedotin) in combination with lenalidomide and a rituximab product for the treatment of adults with relapsed or refractory large B-cell lymphoma (LBCL), including diffuse LBCL (DLBCL) and high-grade B-cell lymphoma (HGBL), after at least two prior systemic therapies. According to the company, approval was based on results from the Phase III ECHELON-3 study, which demonstrated a significant reduction in the risk of death in patients treated with Adcetris compared to placebo.¹

“Patients with large B-cell lymphoma can face a challenging journey, with too many patients enduring multiple rounds of chemotherapy and even CAR T therapy with limited success,” said Craig Portell, associate professor, University of Virginia, principal investigator of the trial, in a press release. “For patients who have previously faced setbacks with other therapies, Adcetris provides a new therapeutic option with outpatient administration and proven safety and efficacy.”

The ongoing, randomized, double-blind, multicenter ECHELON-3 trial evaluated Adcetris plus lenalidomide and rituximab versus lenalidomide and rituximab plus placebo. The trial enrolled 230 patients across North America, Europe, and Asia, including those with hard-to-treat subtypes, such as double hit or triple hit lymphoma and transformed disease. The primary endpoint is overall survival (OS) in the intent to treat population, while secondary endpoints include progression-free survival (PFS) and objective response rate (ORR) as assessed by investigator, complete response rate, duration of response, safety, and tolerability.

Detailed findings from ECHELON-3 were published in JCO Oncology Practice and presented at ASCO 2024.1

Results found that Adcetris demonstrated a 37% reduction in risk of death compared to placebo. Additionally, the treatment demonstrated consistent OS benefit regardless of CD30 expression and improvements in PFS and ORR. Notable treatment-related adverse events included neutropenia, thrombocytopenia, and anemia. The safety profile of Adcetris was reported to be consistent with its known profile.

According to Pfizer, over 25,000 cases of DLBCL are diagnosed in the United States annually, representing 25% of all lymphoma cases. An additional 40% have relapsed or have refractory disease after frontline treatment.¹

According to the American Cancer Society, non-Hodgkin lymphoma (NHL) accounts for 4% of all cancers in the United States, making it one of the most common types of the disease. By the end of 2025, it is estimated that 80,350 people will be diagnosed with NHL, with approximately 19,390 deaths. While both men and women can develop the disease, men have a higher propability, with a one in 44 risk, whereas women have a one in 54 risk. While NHL is a more common cancer in children, teens, and young adults, the risk of developing it increases with age. A majority of all reported cases of NHL are in patients over 65 years of age^.2

“Each year, more than 3,500 patients in the US with this aggressive form of non-Hodgkin lymphoma experience treatment failure or relapse after two prior lines of therapy,” said Roger Dansey, MD, chief oncology officer, Pfizer, in the press release. “[This] approval further reinforces the important role of Adcetris as an existing standard of care with overall survival improvement shown for certain types of lymphomas, and now allows physicians to have an option beyond chemotherapy or CAR Ts for patients with relapsed/refractory large B-cell lymphoma.”

References

1. U.S. FDA Approves Pfizer’s ADCETRIS® Combination Regimen for the treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma. Pfizer. February 12, 2025. Accessed February 14, 2025. https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-adcetrisr-combination-regimen

2. Key Statistics for Non-Hodgkin Lymphoma. American Cancer Society. Accessed February 14, 2025. https://www.cancer.org/cancer/types/non-hodgkin-lymphoma/about/key-statistics.html