A prognostic index predicting survival in transformed Waldenström macroglobulinemia

Abstract

Histological transformation into diffuse large B-cell lymphoma is a rare complication in patients with Waldenström macroglobulinemia (WM) usually associated with a poor prognosis. The objective of this study was to develop and validate a prognostic index for survival in transformed WM patients. Through this multicenter, international collaborative effort, we developed a scoring system based on data from 133 patients with transformed WM who were evaluated between 1995 and 2016 (training cohort). Univariate and multivariate analyses were used to propose a prognostic index with 2-year survival after transformation as an end-point. For external validation, a data set of 67 patients was used to evaluate the performance of the model (validation cohort). By multivariate analysis, three adverse covariates were identified as independent predictors of 2-year survival after transformation: elevated serum LDH (2 points), platelet count < 100 x 109/L (1 point) and any previous treatment for WM (1 point). Three risk groups were defined: low-risk (0-1 point, 24% of patients), intermediate-risk (2-3 points, 59%, hazard ratio (HR) = 3.4) and high-risk (4 points, 17%, HR = 7.5). Two-year survival rates were 81%, 47%, and 21%, respectively (P < 0.0001). This model appeared to be a better discriminant than the International Prognostic Index (IPI) and the revised IPI (R-IPI). We validated this model in an independent cohort. This easy-to-compute scoring index is a robust tool that may allow identification of groups of transformed WM patients with different outcomes and could be used for improving the development of risk-adapted treatment strategies.

Figure 1.

Kaplan-Meier curves for survival after transformation according to subgroups defined by the transformed Waldenström International Prognostic Index. (A) The model was built using three variables: previous treatment for Waldenström macroglobulinemia, lactate dehydrogenase at transformation and platelet count at transformation. It divided the cohort into three risk groups: low-, intermediate-, and high-risk with 2-year survival rates after transformation of 80.8%, 46.9% and 21.1%, respectively. (B) Validation cohort: 2-year survival after transformation of 71.4%, 39.4% and 0%, for the low-, intermediate-, and high-risk groups, respectively.

Figure 2.

Kaplan-Meier curves for survival after transformation according to risk group as defined by (A) the International Prognostic Index (IPI) and (B) the revised IPI (R-IPI).