FDA Approves Pfizer Combination Regimen for Treating R/R Diffuse Large B-Cell Lymphoma

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FDA has approved the supplemental biologics license application for Pfizer’s ADCETRIS (brentuximab vedotin) in combination with lenalidomide and a rituximab product for treating adult patients with relapsed or refractory large B-cell lymphoma (R/R LBCL), Pfizer announced on Feb. 12, 2025. The additional indication includes patients with diffuse large B-cell lymphoma (DLBCL) not otherwise specified (NOS), DLBCL arising from indolent lymphoma, or high-grade B-cell lymphoma (HGBL), after two or more lines of systemic therapy who are not eligible for autologous hematopoietic stem cell transplantation (auto-HSCT) or chimeric antigen receptor (CAR) T-cell therapy.

Brentuximab vedotin is an antibody-drug conjugate (ADC) that comprises a CD30-directed monoclonal antibody attached by a protease-cleavable linker to monomethyl auristatin E (MMAE), a microtubule disrupting agent. This ADC employs a linker system that is designed to remain stable in the bloodstream but then releases MMAE when internalized by CD30-positive tumor cells.

“Each year, more than 3500 patients in the [United States] 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 a company press release (1). “Today’s 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 [chimeric antigen receptor T cell therapies] for patients with relapsed/refractory large B-cell lymphoma.”

The approval was based on efficacy and safety data from a Phase III study (ECHELON-3), in which the combination regimen demonstrated a statistically significant and clinically meaningful improvement in overall survival in patients with R/R DLBCL (2). The study included patients who were heavily pre-treated, some of whom had previously received CAR-T therapy. Survival benefit was observed irrespective of CD30 expression.

“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 principal investigator Craig Portell, MD, associate professor, University of Virginia, in the 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.”

Overall, brentuximab vedotin (under the brand name, ADCETRIS) is approved in the US in the following eight indications:

• adult patients with R/R LBCL, including DLBCL NOS, DLBCL arising from indolent lymphoma, or HGBL, after two or more lines of systemic therapy, who are not eligible for auto-HSCT or CAR-T cell therapy, in combination with lenalidomide and a rituximab product (2025 approval)
• adult patients with previously untreated Stage III/IV classical Hodgkin lymphoma (cHL) in combination with doxorubicin, vinblastine, and dacarbazine (2018 approval)
• pediatric patients two years and older with previously untreated high risk cHL in combination with doxorubicin, vincristine, etoposide, prednisone, and cyclophosphamide (2022 approval)
• adult patients with cHL who are at high risk of relapse or progression as post-autologous hematopoietic stem cell transplantation (auto-HSCT) consolidation (2015)
• adult patients with cHL after failure of auto-HSCT or after failure of at least two prior multi-agent chemotherapy regimens in patients who are not auto-HSCT candidates (2011 approval)
• adult patients with previously untreated systemic anaplastic large cell lymphoma (sALCL) or other CD30-expressing peripheral T-cell lymphomas (PTCL), including angioimmunoblastic T-cell lymphoma and PTCL not otherwise specified, in combination with cyclophosphamide, doxorubicin, and prednisone (2018 approval)
• adult patients with sALCL after failure of at least one prior multi-agent chemotherapy regimen (2011 approval)
• adult patients with primary cutaneous anaplastic large cell lymphoma or CD30-expressing mycosis fungoides after prior systemic therapy (2017 approval).

Pfizer and Takeda have a collaboration to jointly develop brentuximab vedotin (under the brand name, ADCETRIS). Under their agreement, Pfizer holds US and Canadian commercialization rights while Takeda has rights to commercialize the product in the rest of the world. The two companies are funding joint development costs for this product on a 50/50 basis, excluding Japan, where Takeda is solely responsible for development costs (1).

References

1. Pfizer. US FDA Approves Pfizer’s ADCETRIS Combination Regimen for the treatment of Relapsed/Refractory Diffuse Large B-Cell Lymphoma. Press Release. Feb. 12, 2025.
2. Kim, J. A.; Hahn, U.; Kim, W-S.; et al. Brentuximab Vedotin in Combination with Lenalidomide and Rituximab in Patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma: Results from the Phase 3 ECHELON-3 Study. J. Clin. Oncol. 2024, 42 (17) suppl. DOI: 10.1200/JCO.2024.42.17_suppl.LBA7005