FDA Accepts sBLA for Polatuzumab Vedotin Plus R-CHP in Untreated DLBCL

FDA

The FDA has accepted a supplemental biologics license application (sBLA) for the combination of polatuzumab vedotin-piiq (Polivy) and R-CHP (rituximab [Rituxan], cyclophosphamide, doxorubicin, and prednisone) as a treatment for patients with previously untreated diffuse large B-cell lymphoma (DLBCL).¹

The sBLA is supported by data from the phase 3 POLARIX trial (NCT03274492), which showed that polatuzumab vedotin plus R-CHP demonstrated a 27% reduction in relative risk for disease progression, relapse, or death compared with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) in patients with newly diagnosed DLBCL.²

In findings presented at the 2022 Pan Pacific Lymphoma Conference in July, the 2-year progression-free survival (PFS) rate was 76.7% (95% CI, 72.7%-80.8%) in the polatuzumab vedotin plus R-CHP arm vs 70.2% (95% CI, 65.8%-74.6%) in the R-CHOP arm. These results translate to an absolute difference in PFS of 6.5% (HR, 0.73; 95% CI, 0.57-0.95; P = .02).

“The POLARIX study results suggest that [polatuzumab vedotin] plus R-CHP could transform the treatment of this aggressive malignancy, and we are working with the FDA to bring this combination to newly diagnosed DLBCL patients as soon as possible,” Levi Garraway, MD, PhD, the chief medical officer and head of Global Product Development at Roche, stated in a news release. “We hope it will become the new standard of care for the first-line treatment of DLBCL, potentially reducing the need for subsequent treatments and limiting patient burden.”

In May 2022, the European Commission approved polatuzumab vedotin plus R-CHP for use in adult patients with previously untreated DLBCL based on results from POLARIX.³

The international, randomized, double-blind, placebo-controlled POLARIX study evaluated the efficacy, safety, and pharmacokinetics of polatuzumab vedotin plus R-CHP vs R-CHOP in patients with previously untreated CD20-positive DLBCL.⁴ Patients were required to have an international prognostic index score of 2-5, an ECOG performance status of 0 to 2, a life expectancy of at least 12 months, and adequate hematologic function.

Key exclusion criteria included a history of severe allergic, anaphylactic reactions to humanized or murine monoclonal antibodies, or known sensitivity or allergy to murine products; a contraindication to any of the individual components of CHOP, including prior receipt of anthracyclines; prior organ transplantation; current grade greater than 1 peripheral neuropathy by clinical examination; a history of indolent lymphoma or follicular lymphoma grade 3B; B-cell lymphoma, unclassifiable, with features intermediate between DLBCL and classical Hodgkin lymphoma; primary mediastinal LBCL; or Burkitt lymphoma.

Once enrolled, patients were randomly assigned to 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) or standard-of-care R-CHOP (n = 439). All patients received 375 mg/m2 of rituximab per day for cycles 7 and 8.

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.

Additional data showed that polatuzumab vedotin plus R-CHP elicited an EFS benefit (HR, 0.75; 95% CI, 0.58-0.96; P = .02).2 There was no significant difference between PET-CR rate at end of treatment (78.0% vs 74.0%; P =.16), though DFS results suggested that responses are more durable with the experimental combination (HR, 0.70; 95% CI, 0.50-0.98). There was no significant difference in OS between the treatment arms (HR, 0.94; 95% CI, 0.65-1.37; P = 0.75).

References

1. 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 August 16, 2022. https://bit.ly/3QuHrls
2. 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) therapy in patients with previously untreated diffuse large B-cell lymphoma (DLBCL): results from the phase III POLARIX study. Presented at: 2022 Pan Pacific Lymphoma Conference; July 18-22, 2022; Koloa, HI. https://bit.ly/3PJhGgJ
3. Roche’s Polivy combination approved by European Commission for people with previously untreated diffuse large B-cell lymphoma. News release. F. Hoffman-La Roche Ltd. May 25, 2022. Accessed August 16, 2022. https://bit.ly/3GD0ZQR
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 (POLARIX). ClinicalTrials.gov. Updated May 31, 2022. Accessed August 16, 2022. https://clinicaltrials.gov/ct2/show/NCT03274492