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The European Commission has approved the combination of polatuzumab vedotin and rituximab and cyclophosphamide, doxorubicin, and prednisone for use in adult patients with previously untreated diffuse large B-cell lymphoma.
The European Commission (EC) has approved the combination of polatuzumab vedotin (Polivy) and rituximab (MabThera) and cyclophosphamide, doxorubicin, and prednisone (R-CHP) for use in adult patients with previously untreated diffuse large B-cell lymphoma (DLBCL).1
The regulatory decision was supported by data from the phase 3 POLARIX trial (GO39942; NCT03274492). At a median follow-up of 28.2 months (range, 0.1-43.4), polatuzumab vedotin plus R-CHP significantly improved progression-free survival (PFS) vs R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone), translating to a 27% reduction in the risk of disease progression or death (HR, 0.73; 95% CI, 0.57-0.95; P < .0177).2
The initial conditional marketing authorization of polatuzumab vedotin in the European Union for use in adult patients with relapsed or refractory DLBCL who are not eligible to undergo hematopoietic stem cell transplant has also been converted into a full approval.
“After more than 20 years with very limited treatment advances, the approval of [polatuzumab vedotin] plus R-CHP marks a new era for people battling this aggressive disease,” Levi Garraway, MD, PhD, chief medical officer and head of Global Product Development at Roche, stated in a press release. “We are delighted that the European Commission has approved this [polatuzumab vedotin] regimen and believe it has the potential to make a significant impact on the lives of people with DLBCL.”
Patients with CD20-positive DLBCL who did not receive prior treatment for lymphoma were enrolled to POLARIX. To participate, they were required to be between the ages of 18 years and 80 years, have an ECOG performance status of 0 to 2, an International Prognostic Index (IPI) score between 2 and 5 at baseline, and adequate hematologic, renal, hepatic, and cardiac function.
Those with a history of indolent lymphoma or who had a contraindication to any component of R-CHOP were excluded. Patients who received prior anthracycline agents or who had known central nervous system involvement were not permitted.
Study participants (n = 879) were randomized 1:1 to receive either polatuzumab vedotin in combination with R-CHP (n = 440) or R-CHOP (n = 439). In the first 6 treatment cycles, patients were given polatuzumab vedotin/R-CHP or R-CHOP. On the first day of each cycle, polatuzumab was administered at 1.8 mg/kg with a placebo matching vincristine in the investigative arm. In the control arm, patients received a placebo matching polatuzumab vedotin and vincristine at 1.4 mg/m2, in combination with rituximab at 375 mg/m2, cyclophosphamide at 750 mg/m2, and doxorubicin at 50 mg/m2.
All participants were given oral prednisone at 100 mg once daily on days 1 through 5 of each of the first 6 cycles of treatment. In cycle 7 and 8, all patients received rituximab monotherapy at 375 mg/m2.
Stratification factors included IPI score (2 vs 3 to 5), bulky disease (present vs absent), and geographic region (Western Europe, United States, Canada, and Australia vs rest of world).
Investigator-assessed PFS served as the primary end point of the trial, and key secondary end points comprised investigator-assessed event-free survival (EFS), positron emission tomography and computed tomography (PET-CT)–based complete response (CR) at treatment completion by blinded independent central review, overall survival (OS), and safety.
In the overall population, the median age was 65 years (range, 19-80). Notably, the 2 treatment arms were noted to be well balanced with regard to stratification factors and centrally evaluated disease subsets.
Additional findings revealed a higher percentage of patients who survived without disease progression at 2 years in the investigative arm (76.7%; 95% CI, 72.7%-80.8%) vs the control arm (70.2%; 95% CI, 65.8%-74.6%), a difference that translated to 6.5 percentage points.
Notably, subgroup analyses showed that a clear benefit was not achieved with polatuzumab plus R-CHP vs R-CHOP in following populations: those aged 60 years or younger, those with germinal-center B-cell–like disease, those with bulky disease, and those with lower IPI scores.
Those in the investigative arm experienced a lower rate of EFS at 2 years vs those in the control arm, at 75.6% (95% CI, 71.5%-79.7%) and 69.4% (95% CI, 65.0%-73.8%), respectively (HR, 0.75; 95% CI, 0.58-0.96; P = .02). There was not a statistically significant difference in the percentage of patients who experienced a CR at treatment completion between the 2 arms (78.0% vs 74.0%, respectively; P = .16).
However, those who received polatuzumab vedotin/R-CHP and achieved a CR as their best response to treatment were found to have a higher likelihood of persistent remission compared with those who received R-CHOP and achieved a CR (HR, 0.70; 95% CI, 0.50-0.98). OS was not found to significantly differ between the treatment arms.
At the data cutoff of June 28, 2021, a lower percentage of patients in the investigative arm went on to receive at least 1 subsequent course of therapy for disease vs those in the control arm, at 22.5% and 30.3%, respectively.
The toxicity profile for polatuzumab vedotin plus R-CHP was comparable to that observed with R-CHOP. Most toxicities experienced with the investigative regimen included peripheral neuropathy (52.9%), nausea (41.6%), neutropenia (38.4%), and diarrhea (30.8%).