The overall incidence of peripheral neuropathy was 43
The overall incidence of peripheral neuropathy was 43.6% in the polatuzumab vedotin + BR arm compared with 7.7% in the BR arm (26). Current FDA Label and Boxed Warnings On the basis of the results DprE1-IN-2 from the study by Sehn et al. These approvals were based on a randomized study of patients treated with either polatuzumab vedotin plus BR or BR alone, where complete response was 40% in the polatuzumab vedotin + BR group versus 18% in the DprE1-IN-2 BR group. The most common adverse events of this treatment were cytopenias and peripheral neuropathy. and pneumonia and herpesvirus during treatment with polatuzumab vedotin. Other considerations include prophylactic treatment with granulocyte colony-stimulating factor (G-CSF), as well as tumor lysis syndrome prophylaxis for patients who are at increased risk (22). Dose modifications Dose modifications are recommended for peripheral neuropathy, cytopenias and infusion reactions (22). For peripheral neuropathy that is Grade (Gr) 2C3, it is recommended to hold the medication until improved to Gr 1. If recovery to Gr 1 neuropathy occurs by day 14, polatuzumab vedotin can be resumed at a reduced dose of 1 1.4 mg/kg, and if Gr 2C3 neuropathy continues beyond day 14 polatuzumab vedotin should be permanently discontinued. For Gr 4 peripheral neuropathy, it is recommended that polatuzumab vedotin be completely discontinued (22). For Gr 3C4 neutropenia, it is recommended to hold treatment until ANC 1000/L. If ANC recovers later than 7 days, the healthcare provider can consider using G-CSF prophylactically and dose-reduce polatuzumab vedotin to 1 1. 4 mg/kg if bendamustine has already been NFKB-p50 dose-reduced. Similarly, for Gr 3C4 thrombocytopenia, treatment should be held until platelets recover to 75,000/L, and if thrombocytopenia takes longer than 7 days to recover, polatuzumab vedotin could be dose-reduced to 1 1.4 mg/kg if bendamustine has already been dose-reduced (22). In the event of a Gr 4 infusion reaction, polatuzumab vedotin should be permanently discontinued. For Gr 1C3 infusion reactions, interruption of infusion and supportive treatment is recommended, and infusion may be restarted at 50% of the rate once symptoms have resolved. However, if initial symptoms are Gr 3 (or recurrent Gr 2) wheezing, bronchospasm or generalized urticaria, polatuzumab vedotin should be permanently discontinued (22). Safety and Toxicity In the phase I study led by Palanca-Wessels, single-agent polatuzumab vedotin at the recommended phase II dose of 2.4 mg/kg resulted in Gr 3C4 adverse events (AEs) in 58% of NHL patients. The most common Gr 3C4 AEs were neutropenia (40%), anemia (11%) and peripheral neuropathy (9%). Other common AEs included diarrhea (4%) and respiratory tract infections DprE1-IN-2 (4%). In the cohort treated with polatuzumab vedotin and rituximab, 77% of patients had Gr 3C4 AEs, and the most common AEs were neutropenia (56%), anemia (22%) and febrile neutropenia (22%) (24). In the study combining polatuzumab vedotin with BR, Gr 3C4 hematological toxicities were more common in the investigational arm than in the control BR arm. The most common toxicities in the investigational arm were Gr 3C4 neutropenia (46.2% vs. 33.3%), anemia (28.2% vs. 17.9%) and thrombocytopenia (41% vs. DprE1-IN-2 23.1%), while Gr 3C4 infections were similar in both arms (23.1% vs. 20.5%) (26). Although cytopenias were higher in the polatuzumab vedotin + BR arm than in the BR arm, transfusion rates were no different between both arms. For red blood cells, transfusion rates were 25.6% versus 20.5%, and for platelets they were 15.4% versus 15.4%. Dose reduction of polatuzumab vedotin only occurred in 2 patients in this trial and it was due to Gr 2 peripheral neuropathy. The overall incidence of peripheral neuropathy was 43.6% in the polatuzumab vedotin + BR arm compared with 7.7% in the BR arm (26). Current FDA Label and Boxed Warnings On the basis of the results from the study by Sehn et al. (26), the U.S. Food and Drug Administration (FDA) granted accelerated approval to polatuzumab vedotin (Genentech Inc.; Polivy, polatuzumab vedotin-piiq) on June 6, 2019, and its indication is in combination with BR for adult patients with relapsed or refractory DLBCL after at least two prior therapies (22). The.