FDA Approves Polatuzumab Vedotin-piiq Plus R-CHP For Certain Types of Diffuse Large B-cell Lymphoma

Officials with the FDA have approved polatuzumab vedotin-piiq (Polivy; Roche) in combination with rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for the treatment of adults with previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified, or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index score of 2 or greater.

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This decision converts the accelerated approval of polatuzumab vedotin-piiq in combination with bendamustin and rituximab for relapsed or refractory DLBCL after at least 2 prior therapies to a regular approval, according to a press release.

Polatuzumab vedotin-piiq is a first-in-class, anti-CD79b antibody-drug conjugate. According to investigators, the CD79b protein is expressed specifically in the majority of B cells, which are impacted in some types of non-Hodgkin lymphoma. Polatuzumab vedotin-piiq binds to cancer cells and destroys these B-cells by delivering an anti-cancer agent, which is believed to minimize the impacts on normal cells.

DLBCL is an aggressive and difficult-to-treat disease and is the most common form of Hodgkin lymphoma in the United States, with approximately 31,000 individuals projected to be diagnosed in 2023. Little progress has been made in improving patient outcomes in previously untreated DLBCL. Although many patients respond to initial treatment, as many as 4 in 10 do not respond or relapse.

“It has been nearly 20 years since a new treatment option has become available to people newly diagnosed with diffuse large B-cell lymphoma,” said Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, in a press release. “Today’s decision from the FDA to approve Polivy in combination with R-CHP in this setting brings a much-needed new treatment option which may improve outcomes and bring other benefits to many patients with this aggressive lymphoma.”

For patients who undergo initial treatment with the standard of care rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), most relapses occur within 2 years of starting treatment. Additionally, the majority of those who require subsequent lines of therapy have poor outcomes.

The new approval is based on pivotal data from the POLARIX trial, an international phase 3, randomized, double-blind, placebo-controlled study. The trial included 879 patients randomized 1:1 to receive either polatuzumab vedotin-piiq plus R-CHP plus a vincristine placebo for 6 cycles, followed by rituximab for 2 cycles; or R-CHOP plus a polatuzumab vedotin-piiq placebo for 6 cycles followed by 2 cycles with rituximab. The primary outcome is progression-free survival (PFS).

The trial demonstrated a statistically significant and clinically meaningful improvement in PFS compared to treatment with R-CHOP. The risk of disease progression, relapse, or death was reduced by 27% with polatuzumab vedotin-piiq plus R-CHP compared with R-CHOP, according to the study.

The safety profile was comparable for polatuzumab vedotin-piiq plus R-CHP versus R-CHOP, including rates of grade 3 or 4 adverse events (AEs [57.7% versus 57.5%]), serious AEs (34% versus 30.6%), grade 5 AEs (3% versus 2.3%), and AEs leading to dose reduction (9.2% versus 13%). The most common AEs were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis, whereas the most common grade 3 or 4 AEs were lymphopenia and neutropenia.

REFERENCE

FDA approves Roche’s Polivy in combination with R-CHP for people with certain types of previously untreated diffuse large B-cell lymphoma. News release. Roche. April 19, 2023. Accessed April 20, 2023.