A 20-Year First: FDA Approves First-Line Combo for Diffuse Large B-Cell Lymphoma

The US Food and Drug Administration (FDA) has approved polatuzumab vedotin-piiq (Polivy) in combination with rituximab, cyclophosphamide, doxorubicin and prednisone (R-CHP) for adult patients with untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), or high-grade B-cell lymphoma and who have an International Prognostic Index score of 2 or higher.

The combination is the first FDA-approved first-line therapy in nearly 20 years for the aggressive, hard-to-treat disease, which is the most common form of non-Hodgkin lymphoma in the United States.

The FDA decision on Wednesday converts the accelerated approval to regular approval for polatuzumab vedotin-piig in combination with bendamustine and rituximab for relapsed or refractory (R/R) DLBCL after at least two therapies.

Poor Outcomes on Current Standard Treatment for Most Patients

Nearly 31,000 people in the United States are projected to be diagnosed with DLBCL this year.

The maker of the polatuzumab vedotin-piiq combination therapy, Genentech, notes that little progress has been made in improving patient outcomes in previously untreated DLBCL over the past two decades.

“While many patients are responsive to initial treatment, as many as four in 10 people with DLBCL do not respond or relapse,” the press release states. “For people who undergo initial treatment with the standard of care, [rituximab] plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP), most relapses occur within two years of starting treatment, and the majority of those who require subsequent lines of therapy have poor outcomes.”

Approval Based on POLARIX Trial Results

The FDA approval was based on findings from the phase 3 POLARIX trial, an international phase 3, randomized, double-blind, placebo-controlled study that included 879 patients.

Topline data indicated a 27% reduction in the risk of disease progression, relapse or death with polatuzumab vedotin-piiq plus R-CHP compared with R-CHOP (hazard ratio [HR], 0.73; 95% confidence interval [CI], 0.57-0.95; P <.02).

The safety profiles were similar. In each respective arm, the rates of grade 3 and 4 adverse effects (AEs) were 57.7% vs 57.5%, the rates of serious AEs were 34.0% vs 30.6%, and the rates of grade 5 AEs were 3.0% vs 2.3%.

The most common AEs were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. The most common grade 3/4 AEs were lymphopenia and neutropenia.

The FDA approval follows the FDA Oncologic Drugs Advisory Committee (ODAC) vote on March 9 of 11 to 2 in favor of polatuzumab vedotin-piiq in combination with R-CHP for previously untreated DLBCL.

According to the press release, more than 70 countries have approved this combination for the treatment of adult patients with previously untreated DLBCL, including the EU, UK, Japan, Canada and China.

Additionally, the combination was recently added to the National Comprehensive Cancer Network Clinical Practice Guidelines in Oncology as a category 1, preferred regimen for first-line DLBCL.

The company says the polatuzumab vedotin-piiq combination therapy binds to cancer cells such as CD79b and destroys the B-cells via delivery of an anticancer agent, which is thought to minimize the effects on normal cells.