Purpose: Mounting evidence supports the clinical significance of gene mutations and immunogenetic features in common mature B-cell malignancies.Experimental Design: We undertook a detailed characterization of the genetic background of splenic marginal zone lymphoma (SMZL), using targeted resequencing and explored potential clinical implications in a multinational cohort of 175 patients with SMZL.Results: We identified recurrent mutations in TP53 (16%), KLF2 (12%), NOTCH2 (10%), TNFAIP3 (7%), MLL2 (11%), MYD88 (7%), and ARID1A (6%), all genes known to be targeted by somatic mutation in SMZL. KLF2 mutations were early, clonal events, enriched in patients with del(7q) and IGHV1-2 Ã 04 B-cell receptor immunoglobulins, and were associated with a short median time to first treatment (0.12 vs. 1.11 years; P ¼ 0.01).In multivariate analysis, mutations in NOTCH2 [HR, 2.12; 95% confidence interval (CI), 1.02-4.4; P ¼ 0.044] and 100% germline IGHV gene identity (HR, 2.19; 95% CI, 1.05-4.55; P ¼ 0.036) were independent markers of short time to first treatment, whereas TP53 mutations were an independent marker of short overall survival (HR, 2.36; 95 % CI, 1.08-5.2; P ¼ 0.03). Conclusions:We identify key associations between gene mutations and clinical outcome, demonstrating for the first time that NOTCH2 and TP53 gene mutations are independent markers of reduced treatment-free and overall survival, respectively.

After completing this course, the reader will be able to:1. Describe the effect of the addition of rituximab to standard CHOP chemotherapy on the outcome of patients with primary mediastinal large B-cell lymphoma.2. Explain potential changes in the use of radiotherapy and aggressive chemotherapy in the rituximab era.This article is available for continuing medical education credit at CME.TheOncologist.com. CME CME

Summary The prognostic value of baseline serum free light chain ratio (sFLCR) was investigated in 94 multiple myeloma (MM) patients. sFLCR was calculated as κ/λ or λ/κ, depending on the patients’ dominating monoclonal light chain. Median baseline sFLCR was 3·57 in κ‐MM patients, 45·09 in λ‐MM. ‘High’ sFLCR (≥ the observed median value for κ‐ and λ‐MM respectively) correlated with elevated serum creatinine and lactate dehydrogenase, extensive marrow infiltration and light chain type MM. The 5‐year disease‐specific survival was 82% and 30% in patients with sFLCR lower than and equal or greater than the median, respectively (P = 0·0001). sFLCR was an independent prognostic factor.