Polatuzumab Vedotin plus R-CHP Outperforms R-CHOP as First-Line Therapy in Patients with Diffuse Large B-Cell Lymphoma

JHOP - February 2022 Vol 12, No 1 - ASH Highlights
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Adding the antibody–drug conjugate polatuzumab vedotin to rituximab, cyclophosphamide, doxorubicin, and prednisone (R-CHP) achieved a 27% reduction in the risk for disease progression or death versus standard therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) as first-line therapy for patients with intermediate- or high-risk diffuse large B-cell lymphoma (DLBCL) in the POLARIX study.1

The study also showed that at 24 months, the rate of progression-free survival was significantly better (P <.02) with the R-CHP regimen than with R-CHOP, for an absolute difference of 6.5% favoring polatuzumab vedotin plus R-CHP over standard therapy with R-CHOP.

“With this disease, it can be difficult to achieve a cure in some patients with more extensive disease or older age. Despite the fact that a high percentage [of patients] respond initially to R-CHOP, many ultimately relapse after therapy is completed,” said Gilles Salles, MD, PhD, Medical Oncologist and Chief, Lymphoma Service, Memorial Sloan Kettering Cancer Center, New York City, who discussed the results at a late-breaking session during the 2021 American Society of Hematology annual meeting.

“These results support the use of polatuzumab vedotin plus R-CHP in the initial management of patients with DLBCL,” he added.

Although R-CHOP has been the first-line standard of care for DLBCL for more than 2 decades, it leads to cure in approximately 60% to 70% of patients. Thus far, no new drug or regimen has surpassed the efficacy of first-line R-CHOP for DLBCL, and improved treatments represent an unmet need.

Polatuzumab vedotin was approved by the FDA in 2019 in combination with bendamustine and rituximab for the treatment of patients with relapsed or refractory DLBCL after at least 2 previous lines of therapy. The approval was based on results of a phase 1/2 trial showing that the combination led to complete response rates of 40% versus 18% (P = .026) with the bendamustine plus rituximab arm.

The phase 3 POLARIX clinical trial compared the current standard R-CHOP versus a modified drug regimen that replaces vincristine with polatuzumab vedotin, a CD79b-targeting antibody–drug conjugate.

The study included 879 patients with previously untreated DLBCL from 23 countries who were randomized in a 1:1 ratio to polatuzumab vedotin 1.8 mg/kg plus R-CHP (N = 440) versus R-CHOP plus placebo (N = 439) for six 21-day cycles, followed by 375 mg/m2 of rituximab in cycles 7 and 8.

The patients’ baseline characteristics were well-balanced between the 2 arms (median age, approximately 65 years; 62% had high-intermediate or high-risk International Prognostic Index score; 40% had double-hit lymphoma; and 7% had triple-hit lymphoma).

The results showed a significant improvement in event-free survival and disease-free survival, the secondary end points, with polatuzumab vedotin plus R-CHP compared with R-CHOP.

At the time of this analysis, no difference in 2-year overall survival was found between the 2 arms: 88.7% with the experimental arm versus 88.6% with R-CHOP. The complete responses were 78% and 74%, respectively.

“It is quite satisfying that we were able to improve outcomes without significantly impairing patients’ quality of life,” Dr Salles said.

The 2 treatment arms had similar rates of adverse events. Adverse events of any grade were 97.9% in the polatuzumab vedotin arm versus 98.4% in the R-CHOP arm; grade 3 or 4 adverse events were 57.7% versus 57.5%, respectively. The rates of neutropenia and neuropathy were comparable between the 2 arms.

Adverse events leading to discontinuation occurred in 6.2% of patients on polatuzumab vedotin versus 6.6% of patients on R-CHOP. Dose reduction was reported in 9.2% of patients on polatuzumab vedotin versus 13% of patients on R-CHOP.

Reference

  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. Blood. 2021;138(suppl 2):Abstract LBA-1.
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