The FDA has approved polatuzumab vedotin-piiq (Polivy®, Genentech, Inc.) plus R-CHP (rituximab, cyclophosphamide, doxorubicin, and prednisone) for adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL), not otherwise specified (NOS), or high-grade B-cell lymphoma (HGBL); including those who have an International Prognostic Index (IPI) score of 2 or greater.
Why it matters: "Although most patients (depending on prognostic factors) can be cured with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), up to 40% of patients will have disease that is refractory to this treatment or will have a relapse after an initial response," wrote Hervé Tilly, Professor of Hematology at the University of Rouen, France, and colleagues, in their publication of the results of the POLARIX (NCT03274492) study, on which approval was based. "We conducted the phase 3 POLARIX trial to evaluate the efficacy and safety of polatuzumab vedotin plus R-CHP, as compared with R-CHOP, in patients with previously untreated DLBCL."
Approved population: Adult patients with previously untreated B-cell lymphoma and an IPI score of ≥2.
What they studied: Safety and efficacy were evaluated in the phase 3, double-blind, placebo-controlled study in which patients were randomized 1:1 to receive six 21-day cycles of either polatuzumab vedotin plus R-CHP or polatuzumab vedotin placebo plus R-CHOP followed by two more cycles of single-agent rituximab in both arms. The primary end point measured was progression-free survival, with secondary end points of event-free survival, complete response rate, and overall survival.
What they found:
Adverse events: The most common adverse events experienced by ≥20% of patients treated with polatuzumab vedotin plus R-CHP, not including laboratory abnormalities, were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis. In 53% of patients, peripheral neuropathy developed or worsened. In 58% of these cases, patients experienced resolution of peripheral neuropathy, in a median of 4 months. Serious adverse events occurred in 34% of patients, including febrile neutropenia and pneumonia. Grade 3 to 4 laboratory abnormalities experienced by ≥10% were lymphopenia, neutropenia, hyperuricemia, and anemia.
What's next: Future studies will address survival across patient subgroups and observe the cohorts across a longer follow-up period to study the durability of the remission period in patients who have not progressed.
Conclusion: "Among patients with DLBCL, first-line treatment with the polatuzumab vedotin plus R-CHP combination evaluated in the current trial showed a progression-free survival benefit over the R-CHOP regimen at 2 years and had a similar safety profile," concluded Dr. Tilly and colleagues in their publication.
Instructions: The recommended dosage of polatuzumab vedotin is a 1.8 mg/kg intravenous infusion in combination with R-CHP every 21 days for six cycles. It is also recommended that patients be premedicated with an antihistamine and an antipyretic and receive prophylaxis with a granulocyte colony-stimulating factor.
For More Information
Tilly H, Morschhauser F, Sehn LH, et al (2022). Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med, 386(4):351-363. DOI:10.1056/NEJMoa2115304
Clinicaltrials.gov (2023). 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). NLM identifier: NCT03274492.
Polivy® (polatuzumab vedotin-piiq) prescribing information (2023). Genentech. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761121s008lbl.pdf
US Food and Drug Administration (2023). FDA approves polatuzumab vedotin-piiq for previously untreated diffuse large B-cell lymphoma, not otherwise specified, and high-grade B-cell lymphoma. Available at: https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-polatuzumab-vedotin-piiq-previously-untreated-diffuse-large-b-cell-lymphoma-not
Image credit: Nephron. Licensed under CC BY-SA 3.0
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