The Relative Dose Intensity Changes during Cycles of Standard Regimens in Patients with Diffuse Large B-Cell Lymphoma

SIMPLE SUMMARY: The important role of relative dose intensity (RDI) of first-line chemotherapy in improving the prognosis of diffuse large B-cell lymphoma has been widely known, but no studies have focused on the trajectory of the average RDI (ARDI) during cycles. We explored the patterns of changes in ARDI during chemotherapy cycles and its association with overall survival. Maintaining a high ARDI in each cycle has a prognostic contribution to the outcome up to the sixth cycle, but no effect from the seventh cycle. The negative prognostic impact of significantly lower ARDI in the early part of the regimen could not be counteracted by increasing ARDI in the second half of the regimen. Malnutrition was associated with a significantly poor prognostic pattern of ARDI changes. A better understanding of ARDI trajectories may help with the early identification of deteriorating patients and has potential implications for the personalized prevention of reduced ARDI. ABSTRACT: No studies have focused on the trajectory of the average relative dose intensity (ARDI) during cycles of first-line chemotherapy for patients with diffuse large B-cell lymphoma. To evaluate the impact of attenuating ARDI during cycles on overall survival, we conducted a multi-centre, longitudinal, observational retrospective study. A total of 307 analysable patients were enrolled. Multivariate Cox hazards modelling with restricted cubic spline models revealed prognostic benefits of higher ARDI up to, but not after, cycle 6. According to group-based trajectory modelling, patients were classified into five groups depending on the pattern of ARDI changes. Among these, two groups in which ARDI had fallen significantly to less than 50% by cycles 4–6 displayed significantly poorer prognosis, despite increased ARDI in the second half of the treatment period (log-rank p = 0.02). The Geriatric Nutritional Risk Index offered significant prediction of unfavourable ARDI changes (odds ratio 2.540, 95% confidence interval 1.020–6.310; p = 0.044). Up to cycle 6, maintenance of ARDI in all cycles (but particularly in the early cycles) is important for prognosis. Malnutrition is a significant factor that lets patients trace patterns of ARDI changes during cycles of chemotherapy associated with untoward prognosis.