A 27% reduction in the risk of progression or death was noted when polatuzumab vedotin was added on R-CHP vs R-CHOP for patients with intermediate- or high-risk diffuse large B-cell lymphoma who received treatment in the first line.
Findings from the phase 3 POLARIX study (NCT03274492) that were presented during a press briefing at the 63rd American Society of Hematology Annual Meeting & Exposition indicated that polatuzumab vedotin-piiq (Polivy) plus R-CHP (rituximab [Rituxan], cyclophosphamide, doxorubicin, and prednisone) was superior to standard chemoimmunotherapy for patients with newly diagnosed intermediate- and high-risk diffuse large B-cell lymphoma.1
The results also showed that the 24-month progression-free survival rate was 76.7% with the polatuzumab vedotin regimen vs 70.2% with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone), reflecting an absolute difference of 6.5% (P < .02).
“These results support the use of polatuzumab vedotin plus R-CHP in the initial management of patients with DLBCL,” senior study author Gilles Salles MD, PhD, a medical oncologist and chief of the Lymphoma Service at Memorial Sloan Kettering Cancer Center, said in a presentation of the data.
R-CHOP has been the frontline standard of care for patients with DLBCL for more than 20 years; however, only 60% to 70% of patients are cured with R-CHOP. Moreover, efforts to improve upon R-CHOP have not yet been successful, leaving a significant unmet need for patients with untreated DLBCL.
On June 10, 2019, the FDA granted an accelerated approval to polatuzumab vedotin for use in combination with bendamustine and rituximab (BR) for the treatment of patients with relapsed/refractory DLBCL who have received at least 2 prior therapies.2
The approval of the antibody-drug conjugate was based on results from the phase 1b/2 GO29365 study (NCT02257567), in which 40% of patients who received polatuzumab vedotin plus BR achieved a complete response vs 18% of patients who received BR alone (P = .026).
Moreover, prior findings from a phase 2 study showed that polatuzumab vedotin plus R-CHP was tolerable and elicited encouraging antitumor activity, serving as the basis for the larger, randomized POLARIX study.
The POLARIX trial enrolled patients with previously untreated DLBCL between the ages of 18 and 80 years with an International Prognostic Index (IPI) between 2 and 5 and an ECOG performance score between 0 and 2.
Patients were randomized to 1.8 mg/kg of polatuzumab vedotin plus R-CHP plus a vincristine placebo or R-CHOP plus a polatuzumab vedotin placebo for 6, 21-day cycles followed by 375 mg/m2 of rituximab in cycles 7 and 8.
Baseline characteristics were well balanced between arms. The median patient age was 65 (range, 19-80) years in the polatuzumab vedotin arm vs 66 (range, 19-80) years in the R-CHOP arm. Most patients had high-intermediate and high-risk IPI in the polatuzumab vedotin and R-CHOP arms at 62%, as well as double-hit (38% vs 41%) vs triple-hit lymphoma (8% vs 6%), respectively.
Additional results showed that there was no difference in overall survival between the 2 arms with current follow-up. However, Salles noted that the burden of additional treatment was higher for patients who received R-CHOP.
In terms of safety, any-grade adverse effects (AEs) occurred in 97.9% of patients in the polatuzumab vedotin arm vs 98.4% of patients in the R-CHOP arm; rates of grade 3/4 AEs occurred in 57.7% vs 57.5% of patients, respectively.
Grade 5 AEs were reported in 3% of patients on polatuzumab vedotin vs 2.3% of patients on R-CHOP.
Serious AEs occurred in 34% of patients on polatuzumab vedotin vs 30.6% of patients on R-CHOP.
AEs leading to discontinuation of any study drug occurred in 6.2% of patients on polatuzumab vedotin vs 6.6% of patients on R-CHOP; discontinuation of polatuzumab vedotin or vincristine occurred in 4.4% vs 5% of patients, respectively.
Dose reduction of any study drug was recorded in 9.2% of patients on polatuzumab vedotin vs 13% of patients on R-CHOP.
Notably, the rates of neutropenia and neuropathy were comparable between the treatment arms.
“The safety profiles of polatuzumab vedotin plus R-CHP and R-CHOP were comparable,” concluded Salles.