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FDA approves Polatuzumab Vedotin Plus R-CHP for previously untreated DLBCL

FDA approves Polatuzumab Vedotin Plus R-CHP for previously untreated DLBCL
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This article originally appeared on OncLive. This version has been slightly modified.

The FDA has approved polatuzumab vedotin-piiq (Polivy) plus rituximab (Rituxan), cyclophosphamide, doxorubicin, and prednisone (R-CHP) for use in adult patients with diffuse large B-cell lymphoma ( LDGCB) previously untreated, not otherwise specified (NOS) or high-grade B-cell lymphoma (HGBL) and who have an International Prognostic Index score of two or more.1

The regulatory decision converts the June 2019 accelerated approval of the antibody-drug conjugate (ADC) in combination with bendamustine and rituximab (BR) for the treatment of patients with relapsed or refractory DLBCL who have already received at least 2 therapies in regular therapy.2 This approval was based on data from the Phase 1b/2 GO29365 trial (NCT02257567), in which 40% of patients receiving the polatuzumab vedotin regimen achieved a complete response (CR) compared to 18% of patients in the BR arm alone, meeting the primary endpoint criteria of the study.

The first-line approval is supported by results from the Phase 3 POLARIX trial (NCT03274492), in which polatuzumab vedotin plus R-CHP (n=440) significantly improved progression-free survival (PFS) compared to rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP; n=439) in this patient population.3

The addition of ADC to R-CHP resulted in a 27% reduction in the risk of disease progression, relapse or death compared to R-CHOP (HR, 0.73; 95% CI, 0 .57-0.95; P < .02). Data presented at the 2022 Pan Pacific Lymphoma Conference showed that the 2-year PFS rate in the investigational group was 76.7% (95% CI, 72.7%-80.8%) compared to 70.2% in the control group (95% CI, 65.8%-74.6%).

“It has been nearly 20 years since a new treatment option became available for people newly diagnosed with diffuse large B-cell lymphoma,” said Levi Garraway, MD, PhD, Chief Medical Officer and Global Head of products at Roche, in a press release. Press release. “Today’s decision by the FDA to approve Polivy in combination with R-CHP in this setting provides a much-needed new treatment option that may improve outcomes and bring other benefits to many patients with this condition. aggressive lymphoma.”

The international, randomized, double-blind, placebo-controlled POLARIX study enrolled patients with previously untreated LBCL, an International Prognostic Index score between 2 and 5 representing low-to-intermediate-to-high risk disease , no central nervous system disease and no primary large mediastinum B-cell lymphoma.4

The trial included patients with multiple types of LBCL, including DLBCL NOS, HBCL with MYC And BCL2 and or BCL6 rearrangements, HGBL NOS and other low-grade B-cell lymphomas including T cell/histiocyte rich LBCL, Epstein–Barr virus positive DLBCL, ALK-LBCL positive and DLBCL positive for HHV8.

Participants were randomized 1:1 to receive either polatuzumab vedotin 1.8 mg/kg once daily plus rituximab 375 mg/m2, cyclophosphamide 750 mg/m2 and doxorubicin 50 mg/m2 for six cycles 21 days; or R-CHOP standard of care. All patients received 375 mg/m2 rituximab daily for cycles 7 and 8.

Investigator-assessed PFS served as the primary endpoint of the trial. Primary secondary endpoints included event-free survival (EFS), PET-CT CR rate at end of treatment, disease-free survival (DFS), overall survival (OS), and safety.

Additional data showed that the hazard ratio for EFS with polatuzumab vedotin plus R-CHP vs R-CHOP was 0.75 (95% CI, 0.58-0.96; P = .02). No significant difference between the PET-CR rate at the end of treatment was observed (78.0% versus 74.0%; P = 0.16), although DFS data suggest that responses are more durable with the polatuzumab vedotin combination (HR, 0.70; 95% CI, 0.50-0.98).

No significant difference in OS was observed between treatment arms (HR, 0.94; 95% CI, 0.65-1.37; P = 0.75). At a median follow-up of 39.7 months, median OS was not achieved in either arm. At 2 years, the OS rate was 88.7% in both arms.

The toxicity profile of polatuzumab vedotin plus R-CHP was found to be comparable to that of R-CHOP.1 Grade 3 or 4 adverse effects (AE) were experienced by 57.7% of people in the experimental group and 57.5% of those in the control group; serious AEs occurred in 34.0% and 30.6% of patients, respectively. In addition, grade 5 toxicities were reported in 3.0% of people in the ADC group versus 2.3% of those in the placebo group. Toxicities led to dose reductions for 9.2% of those who received polatuzumab vedotin and 13.0% of those who did not.

The most commonly reported toxicities included peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. Lymphopenia and neutropenia were the most common grade 3 or 4 AEs.

The first-line regulatory approval follows the FDA’s Oncology Drug Advisory Committee vote by 11 to 2 in March 2023 that POLARIX data supports a favorable benefit-risk profile for polatuzumab vedotin in this population.5

The references

  1. (Ad hoc announcement pursuant to Art. 53 LR) FDA approves Roche’s Polivy in combination with R-CHP for people with certain types of previously untreated diffuse large B-cell lymphoma. Press release. Rock. April 19, 2023. Accessed April 19, 2023. https://www.roche.com/media/releases/med-cor-2023-04-19
  2. FDA approves polatuzumab vedotin-piiq for diffuse large B-cell lymphoma. FDA. June 10, 2019. Accessed April 19, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-polatuzumab-vedotin-piiq-diffuse-large-b-cell-lymphoma
  3. Mehta-Shah N, Tilly 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) in patients with untreated diffuse large B-cell lymphoma (DLBCL) before: results of the phase III POLARIX study. Presented at: 2022 Pan Pacific Lymphoma Conference; July 18-22, 2022; Coloa, Hi. https://f5cb18b31bcff05c4c68-a0ad32938c5dd185096ff3214cd552d4.ssl.cf1.rackcdn.com/2089833-1655492027.pdf
  4. A study comparing the efficacy and safety of polatuzumab vedotin with rituximab-cyclophosphamide, doxorubicin, and prednisone (R-CHP) versus rituximab-cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in participants with diffuse large B-cell lymphoma (POLARIS). ClinicalTrials.gov. Updated May 31, 2022. Accessed April 19, 2023. https://clinicaltrials.gov/ct2/show/NCT03274492
  5. Meeting of the Oncology Drug Advisory Committee (ODAC). Youtube. March 9, 2023. Accessed April 19, 2023. https://www.youtube.com/watch?v=zCf87ABhqpU

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