The antibody–drug conjugate polatuzumab vedotin-piiq (Polivy) added to R-CHP (rituximab [Rituxan], cyclophosphamide, doxorubicin, and prednisone) achieved a 27% reduction in the risk for progression or death compared with the standard regimen of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line therapy for patients with intermediate- and high-risk diffuse large B-cell lymphoma (DLBCL). These results were presented during a late-breaking session and featured at a press conference at the ASH 2021 Annual Meeting and Exposition. The investigators also found that the rate of progression-free survival at 24 months was significantly better with the combined experimental regimen versus R-CHOP (P <.02), for an absolute difference of 6.5% favoring polatuzumab vedotin over standard therapy.
“With this disease, it can be difficult to achieve a cure in some patients with more extensive disease or older age. Despite the fact that a high percentage [of patients] respond initially to R-CHOP, many ultimately relapse after therapy is completed. These results support the use of polatuzumab vedotin plus R-CHP in the initial management of patients with DLBCL,” said senior study investigator Gilles Salles, MD, PhD, Medical Oncologist and Chief, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York City, at the meeting.
Although R-CHOP has been the frontline standard of care for DLBCL for more than 2 decades, this leads to cure in approximately 60% to 70% of patients. Thus far, no new drug or regimen has surpassed the efficacy of frontline R-CHOP for DLBCL, and improved treatments represent an unmet need.
Polatuzumab vedotin was approved by the FDA 2 years ago in combination with bendamustine and rituximab for the treatment of patients with relapsed/refractory DLBCL who received ≥2 previous lines of therapy. Approval was based on the results of a phase 1/2 trial showing that the combination led to complete response rates of 40% versus 18% for the bendamustine and rituximab combination, with good tolerability.
The phase 3 POLARIX trial compared standard R-CHOP with a modified drug combination that omits vincristine and includes polatuzumab vedotin, a CD79b-targeting antibody–drug conjugate. Overall, 879 patients with previously untreated DLBCL from 23 countries were enrolled in the trial. Participants were randomized in a 1:1 ratio to receive polatuzumab vedotin 1.8 mg/kg plus R-CHP or R-CHOP plus placebo for six 21-day cycles followed by 375 mg/m2 of rituximab in cycles 7 and 8.
Patients had Eastern Cooperative Oncology Group performance status scores ranging from 0 to 2. Baseline characteristics were well-balanced between the 2 treatment arms. Median age was approximately 65 years. Approximately 62% had high-intermediate and high-risk International Prognostic Index scores, and approximately 40% and 7% had double-hit and triple-hit lymphoma, respectively.
The results showed a significant improvement with polatuzumab vedotin plus R-CHP in terms of secondary end points, event-free survival, and disease-free survival.
At the time of the presentation, no difference in overall survival was observed at 2 years between the study arms (88.7% in the experimental arm vs 88.6% in the R-CHOP arm). Complete responses were achieved in 78% and 74% of patients, respectively.
“It is quite satisfying that we were able to improve outcomes without significantly impairing patients’ quality of life,” Dr Salles commented.
Both treatment arms had similar percentages of patients who experienced adverse events (AEs). Any-grade AEs were reported in 97.9% of patients in the polatuzumab vedotin arm versus 98.4% of patients in the R-CHOP arm; rates of grade 3/4 AEs were 57.7% versus 57.5% of patients, respectively. The rates of neutropenia and neuropathy were comparable between the treatment arms. Grade 5 AEs were reported in 3% of patients on polatuzumab vedotin versus 2.3% of patients on R-CHOP.
Serious AEs were reported in 34% of patients receiving polatuzumab vedotin versus 30.6% of those receiving R-CHOP. AEs leading to treatment discontinuation of any study drug occurred in 6.2% of patients on polatuzumab vedotin and 6.6% of those on R-CHOP. Dose reductions of any study drug were observed in 9.2% of patients receiving polatuzumab vedotin versus 13% of those receiving R-CHOP.
The POLARIX investigators noted that they will continue to follow participants for insights into longer-term outcomes. In addition, they said that patient subgroups are being analyzed to determine subsets more likely to benefit from the investigational combination.