The POLARIX study found patients with diffuse large B-cell lymphoma (DLBCL) had a significantly higher likelihood of survival without disease progression 2 years after receiving a new drug combination known as pola-R-CHP (polatuzumab vedotin-piiq with rituximab, cyclophosphamide, doxorubicin, and prednisone) compared with those who received the standard of care, R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). The findings, presented by Tilly et al at the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition (Abstract LBA-1), represent the first significant improvement over standard of care for newly diagnosed patients with DLBCL reported in more than 2 decades, according to the authors.

Although the trial found no significant difference in complete response rates or overall survival at 2 years, those who received the new drug combination were less likely to need additional treatment compared with those receiving R-CHOP.

“I think this could be a practice-changing result,” said senior study author Gilles Salles, MD, PhD, Chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center. “This is the first randomized phase III study that has shown a benefit in patients with first-line DLBCL. It shows that it is possible to significantly reduce disease progression, including in patients with difficult-to-treat subtypes.”

R-CHOP, the current standard of care, is curative in only about 60% to 70% of patients with newly diagnosed DLBCL. The new study compared R-CHOP to a modified drug combination that omits vincristine and includes polatuzumab vedotin, a CD79b-targeting antibody–drug conjugate. Polatuzumab vedotin was previously approved for patients with relapsed DLBCL.

“With this disease, it can be difficult to achieve a cure in some patients with more extensive disease or older age,” said Dr. Salles, pointing to a need for therapies that work better for higher-risk patients. “Despite the fact that a high percentage [of patients] respond initially to R-CHOP, many ultimately relapse after therapy is completed.”

POLARIX Details

The trial enrolled 879 patients with previously untreated DLBCL in 23 countries. Half of the participants were randomly assigned to receive pola-R-CHP and half were randomly assigned to receive R-CHOP. At 2 years, 76.7% of those receiving pola-R-CHP and 70.2% of those receiving R-CHOP survived without disease progression or relapse. The trial met its primary endpoint, with a 27% reduction in the relative risk of disease progression, relapse, or death associated with pola-R-CHP.

The results also showed a significant improvement with pola-R-CHP in terms of secondary endpoints, event-free survival, and disease-free survival. However, there was no significant difference in the rate of complete response to treatment, which was seen in 78% of those receiving pola-R-CHP and 74% of those receiving R-CHOP, or overall survival at 2 years (88.7% and 88.6% for pola-R-CHP and R-CHOP, respectively). Researchers noted that further follow-up could help elucidate whether pola-R-CHP brings a survival benefit in the longer term. In either case, Dr. Salles said the new regimen should reduce the risk of relapse and help patients avoid intensive treatments such as stem cell transplantation and chimeric antigen receptor T-cell therapy.

Study participants receiving both treatments experienced a similar rate of adverse events, which included low blood cell counts and peripheral neuropathy. The rate of drug dose reduction or drug discontinuation was similar in both groups.

“It is quite satisfying that we were able to improve outcomes without significantly impairing patients’ quality of life,” commented Dr. Salles.

The trial will continue to follow participants for insights into longer-term outcomes. In addition, researchers are analyzing patient subgroups to determine whether tumor biology or other factors may influence which patients are likely to benefit most from the new drug combination.

Disclosure: This international study was sponsored by Genentech, Inc, and F. Hoffmann-La Roche Ltd, and designed by the sponsor in collaboration with the cooperative group LYSA (the Lymphoma Study Association). Dr. Salles has provided consulting and advisory services to Roche and Genentech.