Polatuzumab Vedotin Plus Rituximab Bests R-CHOP in Treatment-Naïve DLBCL

Christopher Flowers, MD

Progression-free survival (PFS) was significantly prolonged with the combination of polatuzumab vedotin (Polivy) plus rituximab (Rituxan), cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) in patients with previously untreated diffuse large B-cell lymphoma (DLBCL).¹

These results, which were presented during the 10th Annual Meeting of the Society of Hematologic Oncology, are from the phase 3 POLARIX study (NCT03274492) showed that there weas a higher proportion of patients with survived beyond 2 years with Pola-R-CHP, and the safety of the 2 regimens was comparable.

“R-CHOP has really been the standard-of-care regimen for first-line diffuse large B cell lymphoma for over 20 years. And this has occurred despite a number of randomized controlled trials in this setting looking at ways to improve upon R-CHOP, and that includes regimens that intensified therapy regimens that substituted other agents,” said Christopher Flowers, MD, Department of Lymphoma-Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center in Houston, during his presentation.

Flowers noted that the preclinical activity of Pola-R-CHP rationalized its exploration in a phase 3 study. POLARIX is a randomized double-blinded study of 839 patients with treatment-naïve DLBCL who were randomized 1:1 to receive either polatuzumab vedotin 1.8mg/kg with R-CHP for 6 cycles that lasted 21 days or R-CHOP. In each regimen, rituximab was dosed at 375 mg/m2 and administered during cycles 7 and 8.

All patients enrolled in the trial were between the ages of 18 and 80 with an International Prognostic Index (IPI) score of 2-5 and an ECOG performance status of 0-2. The patients were stratified by IPI score, bulky disease, and geographic region. Baseline characteristics were well balanced between the 2 treatment arms.

The primary end point explored in the study was PFS, and the secondary end points included event-free survival (EFS), complete response (CR) rate at the end of treatment, disease-free survival (DFS), and overall survival (OS). To determine the safety of the regimen, investigators evaluated the incidence nature and severity of adverse events (AEs).

At a median follow of 28.2 months, Pola-R-CHP achieved a 27% reduction in the relative risk of disease progression, relapse, or death compared with R-CHOP (HR, 0.73l 95% CI, 0.57-0.95; P = .02). The 24-month PFS rate observed with Pola-R-CHP was 76.7% vs 70.2% with R-CHOP.

Findings for the secondary end points showed that Pola-R-CHP led to a longer EFS of 86.6% vs 82.7% in the R-CHOP arm (HR 0.75; 95% CI: 0.58-0.96; P = .02). OS was also prolonged with Pola-R-CHP compared with R-CHOP (HR, 0.94; 95% CI 0.65-1.37; P = .75).

Any-grade AEs occurred in 97.9% of the Pola-R-CHP vs 98.4% of the R-CHOP arm, and grade 3 and 4 events were seen in 57.7% vs 57.5%, respectively. Grade 5 AEs occurred in 3% of the Pola-R-CHP arm vs 2.3% of the R-CHOP arm.

AEs that led to treatment discontinuation occurred in 6.2% of the Pola-R-CHP group compared with 6.6% of the R-CHOP group, and dose reductions were required for 9.2% vs 13.0%, respectively. AEs were related to polatuzumab vedotin in 4.4% of the Pola-R-CHP group and were related to vincristine in 5.0% of the R-CHOP arm.

The most common AEs observed in the study were peripheral neuropathy, nausea, diarrhea, neutropenia, and anemia.

“This schema really shows the overall common adverse events in terms of the peripheral neuropathy. One of the things that was determined early on in the single agent studies of polatuzumab vedotin and some of the combination studies is that the neuropathy appeared to be cumulative, and that neuropathy more likely occurred with 6 cycles of therapy. And, and so that's why only 6 total doses of polatuzumab vedotin was given in this study,” explained Flowers.

Results from POLARIX support the use of Pola-R-CHP in the upfront management of patients with DLBCL, according to Flowers.

_REFERNCES:

_{Flowers C, Tiklly H, Morschhauser F, et al. Polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) versus rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) therapy in patients with previously untreated diffuse large b-cell lymphoma (DLBCL): results from the phase III POLARIX study. Presented at: 10th Annual Meeting of the Society of Hematologic Oncology (SOHO 2022); September 28-October 1, 2022; Houston TX.}