In the phase III POLARIX trial reported in The New England Journal of Medicine, Tilly et al found that polatuzumab vedotin-piiq plus R-CHP (rituximab, cyclophosphamide, doxorubicin, and prednisone) significantly improved progression-free survival vs R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with previously untreated intermediate- or high-risk diffuse large B-cell lymphoma (DLBCL).

As stated by the investigators, “DLBCL is typically treated with R-CHOP. However, only 60% of patients are cured with R-CHOP. Polatuzumab vedotin is an antibody-drug conjugate targeting CD79b, which is ubiquitously expressed on the surface of malignant B cells.”

Study Details

In the international double-blind trial, 879 patients from sites in regions including Western Europe, the United States, Canada, Australia, and Asia were randomly assigned between November 2017 and June 2019 to receive polatuzumab vedotin plus R-CHP (pola-R-CHP; n = 440) or standard R-CHOP (n = 439). Patients were to receive eight 21-day cycles of treatment, consisting of six cycles of pola-R-CHP or R-CHOP and two cycles of rituximab alone. Polatuzumab vedotin at 1.8 mg/kg or placebo was given on day 1 of each of the first six cycles. The primary endpoint was investigator-assessed progression-free survival.

Progression-Free Survival

At data cutoff (June 2021), median follow-up was 28.2 months (range = 0.1–43.4 months).

Progression-free survival at 2 years was 76.7% (95% confidence interval [CI] = 72.7%–80.8%) in the pola-R-CHP group vs 70.2% (95% CI = 65.8%–74.6%) in the R-CHOP group (stratified hazard ratio [HR] = 0.73, 95% CI = 0.57–0.95, P = .02). Subgroups that did not exhibit a clear benefit with pola-R-CHP included patients aged ≤ 60 years, those with the germinal center B-cell–like subtype of DLBCL, those with bulky disease, and those with lower International Prognostic Index scores.

At 2 years, event-free survival was 75.6% (95% CI = 71.5%–79.7%) with pola-R-CHP vs 69.4% (95% CI = 65.0%–73.8%) with R-CHOP (HR = 0.75, 95% CI = 0.58–0.96, P = .02); overall survival (interim analysis) was 88.7% (95% CI = 85.7%–91.6%) vs 88.6% (95% CI = 85.6%–91.6%), respectively (HR = 0.94, 95% CI = 0.65–1.37, P = .75).

Complete response rates at end of treatment on blinded central review were 78.0% vs 74.0% (P = .16).

Adverse Events

Grade ≥ 3 adverse events occurred in 60.7% of patients in the pola-R-CHP group vs 59.8% of the R-CHOP group; the most common grade 3 or 4 adverse events were neutropenia (28.3% vs 30.8%), febrile neutropenia (13.8% vs 8.0%), and anemia (12.0% vs 8.4%). Grade 3 or 4 infections occurred in 15.2% vs 12.6% of patients; grade ≥ 2 peripheral neuropathy occurred in 13.8% vs 16.7%. Serious adverse events occurred in 34.0% vs 30.6%.

Adverse events led to discontinuation of any component of study treatment in 6.2% vs 6.6%, including discontinuation of polatuzumab vedotin in 4.4%. Adverse events led to death in 13 patients in the pola-R-CHP group vs 10 in the R-CHOP group, primarily due to infection (pneumonia in 4 vs 3 patients, sepsis in 1 vs 3 patients).

The investigators concluded, “Among patients with previously untreated intermediate-risk or high-risk DLBCL, the risk of disease progression, relapse, or death was lower among those who received pola-R-CHP than among those who received R-CHOP.”

Disclosure: The study was funded by F. Hoffmann-La Roche/Genentech. For full disclosures of the study authors, visit nejm.org.