The Food and Drug Administration ( FDA ) has approved Polivy ( Polatuzumab vedotin-piiq; Polatuzumab vedotin ) with a Rituximab product, Cyclophosphamide, Doxorubicin, and Prednisone ( R-CHP ) for adult patients who have previously untreated diffuse large B-cell lymphoma ( DLBCL ), not otherwise specified ( NOS ), or high-grade B-cell lymphoma ( HGBL ) and who have an International Prognostic Index ( IPI ) score of 2 or greater.
Approval was based on POLARIX, a randomized, double-blind, placebo-controlled trial in 879 patients with previously untreated large B-cell lymphoma and an IPI score of 2-5.
The trial evaluated the superiority of substituting Polatuzumab vedotin for Vincristine in the R-CHOP ( Rituximab, Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone ) regimen.
Patients were randomized ( 1:1 ) to receive either Polatuzumab vedotin plus R-CHP ( pola + R-CHP ) or R-CHOP for six 21-day cycles, followed by two additional cycles of Rituximab alone in both arms.
The main diagnoses were de novo DLBCL, NOS ( 84% ) and HGBL ( 11% ).
Efficacy was based on investigator-assessed progression-free survival ( PFS ).
Progression-free survival was statistically significantly longer in the pola + R-CHP arm, with a hazard ratio ( HR ) of 0.73 ( 95% CI: 0.57, 0.95; p = 0.0177 ).
This arm also had a statistically significant improvement in modified event-free survival ( HR 0.75; 95% CI: 0.58, 0.96; p=0.0244 ).
No significant difference in complete response rate or overall survival ( HR 0.94; 95% CI: 0.67, 1.33 on final analysis ) was observed.
The most common adverse reactions with pola + R-CHP ( 20% or more ), excluding laboratory abnormalities, were peripheral neuropathy, nausea, fatigue, diarrhea, constipation, alopecia, and mucositis.
Grade 3 to 4 laboratory abnormalities ( 10% or more ) were lymphopenia, neutropenia, hyperuricemia, and anemia.
Peripheral neuropathy developed or worsened in 53% of patients, with resolution in 58% after a median of 4 months.
Serious adverse reactions occurred in 34% of patients, including febrile neutropenia and pneumonia.
The recommended dose of Polatuzumab vedotin is 1.8 mg/kg as an intravenous infusion every 21 days for 6 cycles in combination with R-CHP.
Patients should be premedicated with an antihistamine and antipyretic and receive prophylactic granulocyte colony-stimulating factor. ( Xagena )
Source: FDA, 2023