Certain Predictors Determine Risk for Higher-Grade Lymphoma in MZL

Patients with marginal zone lymphoma (MZL) who have >4 nodal sites at the time of diagnosis have an increased risk for transitioning to higher-grade lymphoma, according to the results of a recent study that determined the main predictors of increased risk for HGT in this patient population (J Clin Oncol. 2018 Oct 12. Epub ahead of print).

“MZLs typically exhibit an indolent course associated with a long natural history. However, a subset of MZLs undergo transformation to higher-grade lymphomas characterized by aggressive behavior and shorter survival,” explained lead investigator Juan Pablo Alderuccio, MD, Hematologist, Sylvester Comprehensive Cancer Center, Miami, Florida, and colleagues.

“Although some reports suggest that patient outcomes significantly improved in the rituximab era, histologic higher-grade transformation (HGT) remains one of the major challenges in managing patients with indolent lymphomas, including MZL,” they added.

Thus, to fill the gap in knowledge about this clinically significant event, Dr Alderuccio and colleagues conducted an analysis of patients with MZL who received treatment at the Sylvester Comprehensive Cancer Center between 1995 and 2016. They used Kaplan-Meier, Cox proportional hazards regression, and competing risk methods to analyze time-to-event outcomes.

A total of 453 patients were included in the analysis; the median age at time of MZL diagnosis was 60.5 years, and most (n = 20; 59%) presented with stage III to IV disease.

HGT to diffuse large B-cell lymphoma occurred in 34 (7.5%) patients, including 7 (21%) diagnosed when they were initially diagnosed with MZL. Median time to HGT was 29 months (range, 1.3-35 months) in 27 incident patients.

Dr Alderuccio and colleagues observed a higher risk for HGT in patients with nodal/splenic MZL. According to the multivariable competing risk analysis, elevated lactate dehydrogenase, having >4 nodal sites, and no achievement of complete remission (CR) after initial treatment were prognostic factors associated with a significantly higher risk for HGT (P <.02).

“International Prognostic Index (IPI), Follicular Lymphoma IPI, and Mucosa-Associated Lymphoid Tissue Lymphoma IPI were only significant predictors of HGT univariably,” they said.

Overall, patients with HGT had shorter survival rates than those without HGT (5-year overall survival rates, 65% vs 86%, respectively; P <.001). Survival was also shorter for patients who presented with HGT within 1 year of their MZL diagnosis compared with those who had HGT at MZL diagnosis combined with those who had HGT >12 months later (4-year overall survival rate, 43% vs 81%; P <.001).

“Failure to achieve CR after initial treatment, elevated lactate dehydrogenase, and more than four nodal sites at the time of MZL diagnosis are the main predictors of increased risk of HGT,” Dr Alderuccio and colleagues concluded.—Hina Khaliq