The European Commission ( EC ) has granted approval of Polivy ( Polatuzumab vedotin ) in combination with Rituximab plus Cyclophosphamide, Doxorubicin, and Prednisone ( R-CHP ) for the treatment of adult patients with previously untreated diffuse large B-cell lymphoma ( DLBCL ).
DLBCL is an aggressive blood cancer and the most common form of non-Hodgkin lymphoma ( NHL ). Each year in Europe, it is estimated that 40,000 people are diagnosed with DLBCL.
While many patients are responsive to initial treatment, four out of ten are not cured with the current standard of care, and the majority of people who require subsequent lines of therapy have poor outcomes.
Most DLBCL relapses occur within 24 months of starting treatment and patients who remain progression-free 24 months following initiation of first-line therapy have favourable survival outcomes.
EC approval was based on results from the phase III POLARIX study, the first trial to show a clinically meaningful improvement in progression free survival ( PFS ), compared to standard of care Rituximab plus Cyclophosphamide, Doxorubicin, Vincristine and Prednisone ( R-CHOP ), in people with previously untreated DLBCL.
All patients were followed for at least 24 months and at a median follow-up of 28.2 months.
The results of the study have shown a 27% reduction in the risk of disease worsening or death with Polivy plus R-CHP compared to R-CHOP in first-line DLBCL ( hazard ratio [ HR ] 0.73; 95% confidence interval [ CI ]: 0.57–0.95; P less than 0.0177 ).
The safety profile was comparable for Polivy plus R-CHP versus R-CHOP.
The most frequently-reported ( greater than or equal to 30% ) adverse events with Polivy plus R-CHP were peripheral neuropathy ( 52.9% ), nausea ( 41.6% ), neutropenia ( 38.4% ), and diarrhoea ( 30.8% ).
In addition to approval, the EC has also converted Polivy's initial conditional marketing authorisation in the EU for the treatment of adult patients with relapsed or refractory DLBCL, who are not candidates for a haematopoietic stem cell transplant, to a full approval.
Polatuzumab vedotin is a first-in-class anti-CD79b antibody-drug conjugate ( ADC ). The CD79b protein is expressed specifically in the majority of B-cells, an immune cell impacted in some types of non-Hodgkin lymphoma, making it a promising target for the development of new therapies.
Polatuzumab binds to cancer cells such as CD79b and destroys these B-cells through the delivery of an anti-cancer agent ( Vedotin ), which is thought to minimise the effects on normal cells.
POLARIX was an international phase III, randomised, double-blind, placebo-controlled study evaluating the efficacy, safety and pharmacokinetics of Polivy plus R-CHP versus R-CHOP in people with previously untreated diffuse large B-cell lymphoma.
Eight-hundred and seventy-nine patients ( 879 ) were randomised 1:1 to receive either Polivy plus R-CHP plus a Vincristine placebo for six cycles, followed by Rituximab for two cycles; or R-CHOP plus a Polivy placebo for six cycles, followed by two cycles of Rituximab.
The primary outcome measure was progression-free survival ( PFS ) as assessed by the investigator using the Lugano Response Criteria for malignant lymphoma.
PFS is a clinically meaningful disease-related outcome for patients with previously untreated DLBCL as it represents the goal of first-line therapy: decreasing the risk of disease worsening. ( Xagena )
Source: Roche, 2022