Personalized risk prediction for event‐free survival at 24 months in patients with diffuse large B‐cell lymphoma

Abstract

We recently defined event-free survival at 24 months (EFS24) as a clinically relevant outcome for patients with DLBCL. Patients who fail EFS24 have very poor overall survival, while those who achieve EFS24 have a subsequent overall survival equivalent to that of the age- and sex-matched general population. Here, we develop and validate a clinical risk calculator (IPI24) for EFS24. Model building was performed on a discovery dataset of 1,348 patients with DLBCL and treated with anthracycline-based immunochemotherapy. A multivariable model containing age, Ann Arbor stage, normalized serum LDH, ALC, ECOG performance status, bulky disease, and sex was identified. The model was then applied to an independent validation dataset of 1,177 DLBCL patients. The IPI24 score estimates the probability of failing to achieve the EFS24 endpoint for an individual patient. The IPI24 model showed superior discriminatory ability (c-statistic = 0.671) in the validation dataset compared to the IPI (c-statistic = 0.649) or the NCCN-IPI (c-statistic = 0.657). After recalibration of the model on the combined dataset, the median predicted probability of failing to achieve EFS24 was 36% (range, 12–88%), and the IPI24 showed an EFS24 gradient in all IPI groups. The IPI24 also identified a significant percentage of patients with high risk disease, with over 20% of patients having a 50% or higher risk of failing to achieve EFS24. The IPI24 provides an individual patient level probability of achieving the clinically relevant EFS24 endpoint. It can be used via electronic apps.

Simplicity at the cost of predictive accuracy in diffuse large B‐cell lymphoma: a critical assessment of the R‐IPI,IPI, andNCCN‐IPI

“…Maurer et al. (2016) used a logistic regression model with continuous variables to calculate the probability of EFS at 24 months and compared the regression model to the IPI model . Consistent with our finding, a large spread of predicted probabilities within each of the IPI groups was noted .…”

“…(2016) reported similar effects using event‐free survival (EFS) at 24 months as endpoint. The EFS at 24 months was chosen since, in other studies, DLBCL survival normalized relative to that of a matched background population at this milestone time point . Maurer et al.…”

Cancer‐specific mortality, cure fraction, and noncancer causes of death among diffuse large B‐cell lymphoma patients in the immunochemotherapy era

“…8,42,43 With these other models, it may be possible to identify very low-risk groups that indeed show clear evidence of a cure. Because we relied on data collected by cancer registries, the risk model that we used to categorize DLBCL cases lacked some useful clinical variables (eg, performance status and serum lactate dehydrogenase level) included in clinical risk models.…”

A diffúz nagy B-sejtes lymphoma modern szemlélete és kezelése

“…Emiatt egy újabb provizórikus prognosztikai rendszert, az IPI24 bevezetését javasolják, amely ezt jól előre tudja jelezni. Az IPI24-ben használt változók: az életkor, az LDH, az abszolút lymphocytaszám, az Ann Arbor stádium, ECOG PS, a 10 cm-nél nagyobb bulky és a nem [27].…”