Development and Validation of Prognostic Models for Treatment Response of Patients with B-Cell Lymphoma: Standard Statistical and Machine-Learning Approaches

<b>Background:</b> Achieving a complete response after therapy is an important predictor of long-term survival in lymphoma patients. However, previous predictive models have primarily focused on overall survival (OS) and progression-free survival (PFS), often overlooking treatment response. Predicting the likelihood of complete response before initiating therapy can provide more immediate and actionable insights. Thus, this study aims to develop and validate predictive models for treatment response to first-line therapy in patients with B-cell lymphomas. <b>Methods:</b> The study used 2763 patients from the Lymphoma and Related Diseases Registry (LaRDR). The data were randomly divided into training (n = 2221, 80%) and validation (n = 553, 20%) cohorts. Seven algorithms: logistic regression, K-nearest neighbor, support vector machine, random forest, Naïve Bayes, gradient boosting machine, and extreme gradient boosting were evaluated. Model performance was assessed using discrimination and classification metrics. Additionally, model calibration and clinical utility were evaluated using the Brier score and decision curve analysis, respectively. <b>Results:</b> All models demonstrated comparable performance in the validation cohort, with area under the curve (AUC) values ranging from 0.69 to 0.70. A nomogram incorporating the six variables, including stage, lactate dehydrogenase, performance status, BCL2 expression, anemia, and systemic immune-inflammation index, achieved an AUC of 0.70 (95% CI: 0.65-0.75), outperforming the international prognostic index (IPI: AUC = 0.65), revised IPI (AUC = 0.61), and NCCN-IPI (AUC = 0.63). Decision curve analysis confirmed the nomogram's superior net benefit over IPI-based systems. <b>Conclusions:</b> While our nomogram demonstrated improved discriminative performance and clinical utility compared to IPI-based systems, further external validation is needed before clinical integration.