|The following article features coverage from the 2021 American Society of Hematology Annual Meeting. Click here to read more of Cancer Therapy Advisor’s conference coverage.|
Polatuzumab vedotin plus rituximab, cyclophosphamide, doxorubicin, and prednisone (Pola-R-CHP) prolonged progression-free survival (PFS), when compared with standard care, in previously untreated diffuse large B-cell lymphoma (DLBCL), according to results from the phase 3 POLARIX trial.
Pola-R-CHP reduced the risk of progression, relapse, or death by 27%, compared with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), said Hervé Tilly, MD, of the University of Rouen in France.
Dr Tilly presented these results at the 2021 American Society of Hematology (ASH) Annual Meeting.1 The study was also published in the New England Journal of Medicine.2
The trial (ClinicalTrials.gov Identifier: NCT03274492) included 879 patients with previously untreated DLBCL. Patients were 18 to 80 years of age, had an International Prognostic Index (IPI) score of 2-5, and an Eastern Cooperative Oncology Group performance status of 0-2.
The patients were randomly assigned to receive Pola-R-CHP for 6 cycles with a vincristine placebo (n=440) or R-CHOP with a polatuzumab vedotin placebo (n=439). All patients received 2 subsequent cycles of rituximab.
The main baseline characteristics were well balanced between the treatment arms, Dr Tilly said. Overall, about 70% of patients were older than 60 years of age, more than 85% had Ann Arbor stage III/IV disease, and more than 60% had either high-intermediate or high-risk disease by IPI.
At a median follow-up of 28.2 months, the risk of disease progression, relapse, or death was reduced by 27% in patients receiving Pola-R-CHP (hazard ratio [HR], 0.73; 95% CI, 0.57-0.95; P <.02).
The 2-year PFS rate was 76.7% in the Pola-R-CHP arm and 70.2% in the R-CHOP arm, for an absolute difference of 6.5%.
Event-free survival was consistent with PFS, showing an improvement with Pola-R-CHP over R-CHOP (HR, 0.75; 95% CI, 0.58-0.96; P =.02).
There were no significant differences in best overall response rates between the Pola-R-CHP and R-CHOP arms. The complete response rates were 86.6% and 82.7%, respectively, and the partial response rates were 9.3% and 11.4%, respectively.
However, disease-free survival results suggested that responses were more durable with Pola-R-CHP (HR, 0.70; 95% CI, 0.50-0.98).
There was no significant difference in overall survival between the treatment arms (HR, 0.94; 95% CI, 0.65-1.37; P =.75).
Compared with the R-CHOP arm, patients in the Pola-R-CHP arm were less likely to receive subsequent anti-lymphoma treatments — 30.3% and 22.5%, respectively. This was true for radiotherapy (13.0% vs 9.3%), systemic therapy (23.5% vs 17.0%), stem cell transplant (7.1% vs 3.9%), and chimeric antigen receptor T-cell therapy (3.6% vs 2.0%).
Safety profiles were comparable between the treatment arms, Dr Tilly said. However, dose reductions were less frequent in the Pola-R-CHP arm than in the R-CHOP arm — 9.2% and 13.0%, respectively.
Grade 3-4 adverse events (AEs) occurred in 57.7% of patients in the Pola-R-CHP arm and 57.5% in the R-CHOP arm. Serious AEs were observed in 34.0% and 30.6%, respectively. Grade 5 AEs occurred in 3.0% and 2.3%, respectively.
The incidence and severity of peripheral neuropathy was similar between the arms. The time to onset and resolution of symptoms was similar as well.
“The positive results of the POLARIX study support the use of Pola-R-CHP in the initial management of this population,” Dr Tilly concluded.
Disclosures: This research was supported by Hoffman-La Roche. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Read more of Cancer Therapy Advisor’s coverage of the ASH 2021 meeting by visiting the conference page.
1. Tilly H, Morschhauser F, Sehn LH, et al. The POLARIX study: Polatuzumab vedotin with 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. Presented at ASH 2021; December 11-14, 2021. Abstract LBA-1.
2. Tilly H, Morschhauser F, Sehn LH, et al. Polatuzumab vedotin in previously untreated diffuse large B-cell lymphoma. N Engl J Med. Published online December 14, 2021. doi:10.1056/NEJMoa2115304