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Risk Factors for Higher-Grade Transformation in Marginal Zone Lymphoma

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Key Points

  • Elevated LDH, more than four nodal sites, and failure to achieve CR after initial treatment were independent predictors of higher-grade transformation.
  • Higher-grade transformation was associated with poorer overall survival.

In a single-institution study reported in the Journal of Clinical Oncology, Alderuccio et al found that not achieving complete remission (CR) after initial treatment, elevated lactate dehydrogenase (LDH), and more than four nodal sites at marginal zone lymphoma diagnosis are predictive of transformation to higher-grade lymphoma.  

Study Details

The study involved data from 453 patients with marginal zone lymphoma seen at the University of Miami Sylvester Comprehensive Cancer Center between 1995 and 2016. Cumulative incidence rates of higher-grade transformation were estimated using competing risk methods, with death as the competing risk.

Risk Factors for Higher-Grade Transformation

Of the 453 patients, 34 (7.5%) had higher-grade transformation to diffuse large B-cell lymphoma, with 7 of these (21%) diagnosed at the time of marginal zone lymphoma diagnosis. Among the 27 patients with incident higher-grade transformation, median time to transformation was 29 months (range = 1.3–135 months). Increased risk of higher-grade transformation was associated with nodal/splenic marginal zone lymphoma (subdistribution hazard ratio [SHR] = 2.60, P = .023).

On multivariable competing risk analysis, elevated LDH (SHR = 2.71, P = .011), more than four nodal sites (SHR = 2.97, P = .017), and failure to achieve CR after initial treatment (SHR = 3.76, P = .001) were associated with significantly increased risk for higher-grade transformation. International Prognostic Index (IPI), Follicular Lymphoma IPI (FLIPI), and Mucosa-Associated Lymphoid Tissue Lymphoma IPI (MALT-IPI) were significant predictors only in univariate analysis.

Effect on Survival

On multivariate analysis, higher-grade transformation (time dependent) was associated with poorer overall survival (HR = 3.97, P < .001). Overall survival at 5 years was 65% among patients with higher-grade transformation vs 86% among those without higher-grade transformation (P < .001). Four-year overall survival was 43% among patients developing higher-grade transformation within 12 months of marginal zone lymphoma diagnosis vs 81% among those with higher-grade transformation at marginal zone lymphoma diagnosis or who developed higher-grade transformation at > 12 months after marginal zone lymphoma diagnosis (P < .001). Absence of CR and higher scores on IPI, FLIPI, and MALT-IPI were significant predictors of shorter progression-free and overall survival on multivariate analysis.

The investigators concluded, “Failure to achieve CR after initial treatment, elevated lactate dehydrogenase, and more than four nodal sites at the time of [marginal zone lymphoma] diagnosis are the main predictors of increased risk of [higher-grade transformation]. Patients with [higher-grade transformation] have shorter [overall survival].”

The study was supported by the Dwoskin, Recio and Anthony Rizzo Family Foundations and Jaime Erin Follicular Lymphoma Research Consortium.

Izidore S. Lossos, MD, of the University of Miami Sylvester Comprehensive Cancer Center, is the corresponding author for the Journal of Clinical Oncology article.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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