FDA Approves Polatuzumab Vedotin/R-CHP Combo in Previously Untreated DLBCL

The FDA has granted approval to polatuzumab vedotin-piiq (Polivy) in combination with rituximab (Rituxan), cyclophosphamide, doxorubicin, and prednisone (R-CHP) as a treatment for patients with previously untreated diffuse large B-cell lymphoma (DLBCL), according to a press release from Genentech.¹

"This approach with [polatuzumab plus R-CHP] is a first-line therapy that can cure patients and reduce the need for having any subsequent therapy," according to an expert from The University of Texas MD Anderson Cancer Center.

The approval also includes patients with DLBCL not otherwise specified, or who have high-grade B-cell lymphoma, and who have an International Prognostic Index of 2 or greater.

The approval was supported by findings from the phase 3 POLARIX trial (NCT03274492). Topline data indicated a 27% reduction in the risk of disease progression or death with polatuzumab vedotin plus R-CHP compared with R-CHOP (HR, 0.73; 95% CI, 0.57-0.95; P <.02). In each respective arm, the rates of grade 3 and 4 adverse effects (AEs) were 57.7% vs 57.5%, the rates of serious AEs were 34.0% vs 30.6%, and the rates of grade 5 AEs were 3.0% vs 2.3%. The most common grade 3/4 AEs lymphopenia and neutropenia.

According to findings from the POLARIX trial published in The New England Journal of Medicine, polatuzumab plus R-CHP produced a 2-year progression-free survival (PFS) rate of 76.7% (95% CI, 72.7%-80.8%) vs 70.2% (95% CI, 65.8%-74.6%) with R-CHP plus vincristine (R-CHOP; HR, 0.73; 95% CI, 0.57-0.95; P = .02).² Additionally, 2-year overall survival (OS) rates were 88.7% (95% CI, 85.7%-91.6%) and 88.6% (95% CI, 85.6%-91.6%) in each respective arm (HR, 0.94; 95% CI, 0.65-1.37; P = .75).

“Patients who were eligible for the [phase 3 POLARIX trial] with [DLBCL] received a benefit across the board from this treatment,” Christopher R. Flowers, MD, MS, FASCO, said in an interview with CancerNetwork^® ahead of the approval. “That benefit in [PFS] is a meaningful benefit.”

Flowers, a professor and chair in the Department of Lymphoma/Myeloma and interim division head of the Division of Cancer Medicine at The University of Texas MD Anderson Cancer Center, spoke about what the polatuzumab regimen offers to patients as a first-line therapy option compared with other treatments.

“[There are] other therapies like autologous stem cell transplantation, CAR T-cell therapies, and others that are now available in the second or later line for patients with [DLBCL,]” Flowers said. “Those are approaches that can help to prolong [OS], but those are also approaches that are associated with toxicity. This approach with [polatuzumab plus R-CHP] is a first-line therapy that can cure patients and reduce the need for having any subsequent therapy.”

Investigators of the double-blind, placebo-controlled, international phase 3 POLARIX trial randomly assigned 879 patients 1:1 to either the polatuzumab vedotin plus R-CHP arm (n = 440) or the R-CHOP arm (n = 439). Patients received either regimen for 6 cycles followed by rituximab monotherapy for the next 2 cycles.

The primary end point of the trial was investigator-assessed PFS. Secondary end points included OS, event-free survival (EFS), disease-free survival, and safety.

Patients 18 to 80 years old with previously untreated CD20-positive DLBCL and availability of archival or freshly collected tumor tissue were eligible for enrollment on the trial. Additional eligibility criteria included having an ECOG performance status of 0 to 2, a life expectancy of at least 12 months, and adequate hematologic function.

The 2-year EFS rate was 75.6% (95% CI, 71.5%-79.7%) with polatuzumab plus R-CHP vs 69.4% (95% CI, 65.0%-73.8%) with R-CHOP (HR, 0.75; 95% CI, 0.58-0.96; P = .02). In terms of DFS, patients who received polatuzumab plus R-CHP and had a complete response (CR) as their best response were more likely to have persistent disease remission compared with those who received R-CHOP and had a CR (HR, 0.70; 95% CI, 0.50-0.98).

The most common grade 3/4 AEs in the polatuzumab plus R-CHP and R-CHOP arms, respectively, included neutropenia (28.3% vs 30.8%), febrile neutropenia (13.8% vs 8.0%), and anemia (12.0% vs 8.4%). Overall, 6.2% and 6.6% of patients in each respective arm had AEs leading to treatment discontinuation. Of these patients, 4.4% in the experimental arm discontinued polatuzumab due to AEs, and 5.0% in the comparator arm discontinued vincristine due to AEs.

The FDA previously accepted the supplemental biologics license application for polatuzumab plus R-CHP in DLBCL based on findings from the phase 3 POLARIX trial in August 2022.³

References

1. FDA approves Genentech’s Polivy in combination with R-CHP for people with certain types of previously untreated diffuse large B-cell lymphoma. News release. Genentech. April 19, 2023. Accessed April 19, 2023. bit.ly/3N0LiYG
2. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab Vedotin in Previously Untreated Diffuse Large B-Cell Lymphoma. N Engl J Med. 2022;386(4):351-363. doi:10.1056/NEJMoa2115304
3. FDA accepts supplemental biologics license application for Roche’s Polivy combination for people with previously untreated diffuse large B-cell lymphoma. News release. Roche. August 16, 2022. Accessed March 24, 2023. https://bit.ly/3C9QELH