Phase 3 findings from the POLARIX trial showed that the addition of platuzumab vedotin to rituximab, cyclophosphamide, doxorubicin, and prednisone resulted in a 27% reduction in risk of disease progression, relapse, or death for patients with newly diagnosed diffuse large B-cell lymphoma.
Phase 3 findings from the POLARIX (NCT03274492) trial showed that a combination of polatuzumab vedotin-piiq (Polivy) to the regimen of rituximab (Rituxan), cyclophosphamide, doxorubicin, and prednisone (pola-R-CHP) resulted in a 27% reduction in risk of disease progression, relapse, or death for patients compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).
The data were presented in a poster at the 2022 Pan Pacific Lymphoma Conference.1
At 2 years, the progression-free survival (PFS) rate was 76.7% (95% CI, 72.7%-80.8%) in the experimental arm compared with 70.2% (95% CI, 65.8%-74.6%) with R-CHOP, translating into an absolute difference in PFS of 6.5% (HR, 0.73; 95% CI, 0.57-0.95; P = .02).
Investigators in POLARIX administered 1.8 mg/kg of polatuzumab vedotin once per day plus 375 mg/m2 of rituximab, 750 mg/m2 of cyclophosphamide, and 50 mg/m2 of doxorubicin for six 21-day cycles (n = 440). The control arm included 439 patients assigned to R-CHOP, the current standard of care. All patients received 375 mg/m2 of once-daily rituximab for cycles 7 and 8.
In this double-blind, placebo-controlled international trial, eligible adults aged 18 to 80 years were required to have previously untreated DLBCL and an International Prognostic Index (IPI) of 2 to 5. Eligible patients also had an ECOG performance score of 0 to 2. Patients were further stratified by IPI score (2 vs 3-5), bulky disease (<7.5 cm vs ≥7.5 cm), and geographic region (Western Europe, United States, Canada, and Australia vs Asia vs rest of the world).
The primary end point was investigator-assessed PFS. Key secondary end points included event-free survival (EFS), end-of-treatment PET-CT complete response (CR) rate, disease-free survival (DFS), overall survival (OS), and safety.
Median patient age was 65.0 years (range, 19-80) in the experimental arm and 66.0 (range, 19-80) for the control. Just over half of patients in both groups were male and 44% in both groups had bulky disease. In the pola-R-CHP arm, 85% of patients had an ECOG score of 0 or 1 and 38% had an IPI score of 2 compared with 83% and 38%, respectively, in the R-CHOP arm.
Investigators found that EFS favored the pola-R-CHP arm (HR, 0.75; 95% CI, 0.58-0.96; P = .02). There was no significant difference between PET-CR rate at end of treatment (78.0% vs 74.0%; P =.16). However, investigators found that DFS results (HR, 0.70; 95% CI, 0.50-0.98) suggested that responses are more durable with the experimental combination.
There was no difference in OS between the treatment arms (HR, 0.94; 95% CI, 0.65-1.37; P = 0.75). However, fewer patients in the pola-R-CHP arm required subsequent anti-lymphoma therapies.
The incidence of grade 3/4 adverse effects (AEs) was 57.7% in the pola-R-CHP arm vs 57.5% in the R-CHOP arm. Thirty-four percent of patients in the experimental arm experienced serious AEs compared with 30.6% with R-CHOP.
Thirteen (3.0%) patients experienced grade 5 AEs with pola-R-CHP compared with 10 (2.3%) in the control group. However, patients in the pola-R-CHP arm were less likely to require dose discontinuations (4.4% vs 5.0%) or dose reductions (9.2% vs 13.0%).
In May 2022, the European Commission approved pola-R-CHP in this patient population based on findings from POLARIX.2
“The approval of Polivy plus R-CHP in the first-line setting is great news for people in the EU diagnosed with this aggressive lymphoma, giving them a greater opportunity for positive outcomes,” said Hervé Tilly, MD, PhD, POLARIX principal investigator and professor of haematology at the University of Rouen, stated in a press release at the time. “Treatment with this regimen has been shown to reduce the chance of relapse and therefore need for subsequent treatments, limiting the burden of DLBCL.”
The FDA approved polatuzumab vedotin in combination with bendamustine and a rituximab product in June 2019. The combination is indicated for adult patients with relapsed/refractory DLBCL not otherwise specified after at least 2 prior therapies.3
Approval was based on data from the open-label, multicenter Study GO29365 trial (NCT02257567), of 80 patients with relapsed/refractory DLBCL who previously received at least 1 prior regimen. Investigators randomly assigned patients to polatuzumab vedotin plus bendamustine and a rituximab product (BR) or BR for six 21-day cycles.
Forty percent (95% CI, 25%-57%) of patients in the polatuzumab vedotin arm had a CR with compared with 18% (95% CI, 7%-33%) with BR alone. Best overall response rate also favored the experimental combination, at 63% vs 25%, respectively. Of the 25 patients who achieved partial or complete response with the triplet, 16 (64%) had response durations of at least 6 months and 12 (48%) had response durations of at least 12 months.