On April 19, 2023, polatuzumab vedotin-piiq was approved for use with a rituximab product, cyclophosphamide, doxorubicin, and prednisone (R-CHP) for patients with diffuse large B-cell lymphoma (DLBCL)–not otherwise specified or those with high-grade B-cell lymphoma who have an International Prognostic Index score of 2 or greater.1
Supporting Efficacy Data
Approval was based on findings from the double-blind multicenter POLARIX trial (ClinicalTrials.gov identifier NCT03274492), in which 879 patients were randomly assigned to receive polatuzumab vedotin plus R-CHP (n = 430) or R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone; n = 429) for six 21-day cycles, followed by two additional cycles of rituximab alone in both groups. The main diagnoses were de novo DLBCL–not otherwise specified (84%) and high-grade B-cell lymphoma (11%).
Progression-free survival events occurred in 24% vs 31% of patients (hazard ratio [HR] = 0.73, 95% confidence interval [CI] = 0.57–0.95, P = .0177). The polatuzumab vedotin plus R-CHP group also had significant improvement in modified event-free survival (HR = 0.75, 95% CI = 0.58–0.96, P = .0244). No significant differences in complete response rate (78% vs 74%, P = .1557) or overall survival (HR = 0.94, 95% CI = 0.67–1.33) on final analysis were observed.
How It Is Used
The recommended dose of polatuzumab vedotin is 1.8 mg/kg via intravenous infusion every 21 days for six cycles in combination with R-CHP. Patients should be premedicated with an antihistamine and antipyretic and receive prophylactic granulocyte colony–stimulating factor.
Safety Profile
In the POLARIX study, the most common adverse events of any grade in the polatuzumab vedotin plus R-CHP group were peripheral neuropathy (53% vs 54% in R-CHOP group), nausea (42% vs 37%), fatigue (37% vs 38%), diarrhea (31% vs 20%), constipation (29% vs 29%), alopecia (24% vs 24%), and mucositis (22% vs 19%). The most common grade 3 or 4 adverse events in the polatuzumab vedotin plus R-CHP group included febrile neutropenia (15%) diarrhea (3.9%), and fatigue (2.5%). The most common grade 3 or 4 laboratory abnormalities were lymphopenia (44%), neutropenia (39%), and increased uric acid (18%).
KEY POINTS
- Polatuzumab vedotin-piiq was approved for use with R-CHP for patients with DLBCL–not otherwise specified or those with high-grade B-cell lymphoma who have an International Prognostic Index score of 2 or greater.
- The recommended dose of polatuzumab vedotin is 1.8 mg/kg via intravenous infusion every 21 days for six cycles in combination with R-CHP.
Serious adverse events occurred in 34% of patients in the polatuzumab vedotin plus R-CHP group, most commonly febrile neutropenia and pneumonia (≥ 5%). Adverse events led to discontinuation of polatuzumab vedotin in 4.4% of patients. Fatal adverse events occurred in 3.0% of patients in the polatuzumab vedotin plus R-CHP group, including pneumonia (0.9%) and sepsis (0.2%).
Polatuzumab vedotin has warnings/precautions for peripheral neuropathy, infusion-related reactions, myelosuppression, serious and opportunistic infections, progressive multifocal leukoencephalopathy, tumor-lysis syndrome, hepatotoxicity, and embryofetal toxicity. Patients should be advised not to breastfeed while receiving polatuzumab vedotin.
REFERENCE
1. Polivy (polatuzumab vedotin-piiq) for injection, for intravenous use, prescribing information, Genentech, Inc, April 2023. Available at https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761121s008lbl.pdf. Accessed May 10, 2023.
