Analysis of peripheral neuropathy (PN) using clinician- and patient-reported outcomes (ClinRO and PRO) in the POLARIX study.

Abstract

7561 Background: PN is an identified risk of anti-microtubule agents, including polatuzumab vedotin and vincristine. POLARIX (NCT03274492), a Phase III randomized, double-blind, placebo-controlled study comparing Pola-R-CHP with R-CHOP, demonstrated improved progression-free survival (PFS) with Pola-R-CHP (Tilly et al. NEJM 2022). Here, we evaluate the impact of Pola-R-CHP vs R-CHOP on PN using ClinRO and PRO data. Methods: Patients with previously untreated diffuse large B-cell lymphoma (DLBCL) received Pola-R-CHP or R-CHOP. ClinRO data were based on PN grading according to the NCI CTCAE v4.0. PRO data were generated from assessment of patient-reported PN symptoms at baseline and Day 1 of each cycle using the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group – Neurotoxicity (FACT-GOG/NTX) subscale, ranging from 0–44, with higher scores representing lower levels of PN (minimal clinically important difference: 1.38–3.68 [Cheng et al. Health Qual Life Outcomes 2020]). Results: At baseline, ClinRO and PRO symptom scores showed low PN burden (Table). Overall incidence of PN was comparable between treatment arms (Pola-R-CHP: 52.9%; R-CHOP: 53.9%); most events were grade 1, and incidence of grade 2 (Pola-R-CHP: 12.2%; R-CHOP: 15.5%) and grade 3 (Pola-R-CHP: 1.6%; R-CHOP: 1.1%) events were comparable between treatment arms. FACT-GOG/NTX survey completion was high in both arms (96% at baseline; >80% at other timepoints). When evaluated by cycle, ClinRO and PRO demonstrated that more patients experienced earlier onset PN with R-CHOP than with Pola-R-CHP (Table), with ̃10% more R-CHOP- than Pola-R-CHP-treated patients having clinician-reported PN in Cycle (C) 2–5, and a ̃+1-point difference (i.e. fewer symptoms) in PRO symptom scores in C3–6 with Pola-R-CHP vs R-CHOP; by C8+, and during follow up, rates and symptoms of PN were similar. PN symptoms resulted in fewer dose reductions (3.9% vs 8.2%) and drug discontinuations (0.7% vs 2.1%) with Pola-R-CHP vs R-CHOP. Duration of PN was similar for both treatments. Conclusions: In the POLARIX study, Pola-R-CHP did not result in different rates or severity of PN vs R-CHOP. According to ClinRO and PRO data, PN occurred later following initial exposure to Pola-R-CHP than to R-CHOP, and there were fewer dose modifications with Pola-R-CHP than with R-CHOP. Overall, the risk of PN was manageable. Clinical trial information: NCT03274492. [Table: see text]