The Prognostic Impact of Relative Dose Intensity of Vincristine in R-CHOP for Untreated Patients with Diffuse Large B-Cell Lymphoma: A Supplementary Analysis of JCOG0601

Introduction R-CHOP (rituximab, cyclophosphamide [CY], doxorubicin [DXR], vincristine [VCR], and prednisolone) is the standard of care for diffuse large B-cell lymphoma (DLBCL) and cures around 60% of patients. However, some DLBCL survivors suffer from long-lasting peripheral neuropathy (PN) caused by VCR, and the dose of VCR is usually decreased to prevent severe PN. Though, there is a lack of information regarding the effect of VCR dose reduction on DLBCL prognosis, especially based on data from prospective clinical trials. Recently, VCR dose reduction was not associated with poor prognosis in patients with aggressive B-cell lymphomas, based on the results of the RICOVER-60 trial (NCT00052936) (Bewarder et al., Haematologica 2023). In this trial, R-CHOP was administered in 14-day cycles. To evaluate the clinical impact of relative dose intensity (RDI) of VCR (RDI O) in patients with DLBCL treated with tri-weekly R-CHOP (R-CHOP21), we conducted a supplemental analysis of the JCOG0601: randomized phase II/III trial of the Japan Clinical Oncology Group (jRCTs031180139). In the JCOG0601 trial, RW-CHOP21 (CHOP21 with eight doses of weekly rituximab) and R-CHOP21 were compared for progression-free survival (PFS) (Ohmachi et al., Blood Adv. 2021). Methods Between 2007 and 2014, 422 patients were enrolled in the JCOG0601 trial. Among them, 401 patients who received at least six courses of R-CHOP21 (n=206) or RW-CHOP21 (n=195) were eligible for this supplemental analysis. Those who could not complete six courses of chemotherapy were excluded because their treatment outcomes might be impaired mainly due to their disease aggressiveness and not the dose intensity of chemotherapy. As PFS was not significantly different between the two treatment arms, these 401 patients were analyzed together (Figure A). The impact of decreased RDI O on PFS was assessed using the Cox proportional hazard model and two-sided log-rank p-values with several cutoff values of RDI O (95, 90, 85, 80, 70, 60, or 50%). The VCR dose was reduced according to the protocol. As a subgroup analysis, the impact of RDI O was evaluated in patients whose RDI of CY and DXR (RDI C+H) were retained, defined as RDI C+H were both ≥85% (high RDI C+H), or not retained, defined as either or both of RDI C+H were