Gene expression and copy number profiling of follicular lymphoma biopsies from patients treated with first-line rituximab without chemotherapy.

The Nordic Lymphoma Study Group has performed two randomized clinical trials with chemotherapy-free first-line treatment (rituximab +/- interferon) in follicular lymphoma (FL), with 73% of patients alive and 38% without any need of chemotherapy after 10.6 years median follow-up. In order to identify predictive markers, that may also serve as therapeutic targets, gene expression- and copy number profiles were obtained from 97 FL patients using whole genome microarrays. Copy number alterations (CNAs) were identified, e.g. by GISTIC. Cox Lasso Regression and Lasso logistic regression were used to determine molecular features predictive of time to next therapy (TTNT). A few molecular changes were associated with TTNT (e.g. increased expression of INPP5B, gains in 12q23/q24), but were not significant after adjusting for multiple testing. Our findings suggest that there are no strong determinants of patient outcome with respect to GE data and CNAs in FL patients treated with a chemotherapy-free regimen (i.e. rituximab +/- interferon).

Follicular lymphoma in Sweden: nationwide improved survival in the rituximab era, particularly in elderly women: a Swedish Lymphoma Registry study.

Treatment for follicular lymphoma (FL) improved with rituximab. In Sweden, first-line rituximab was gradually introduced between 2003 and 2007, with regional differences. The first national guidelines for FL were published in November 2007, recommending rituximab in first-line therapy. Using the population-based Swedish Lymphoma Registry, 2641 patients diagnosed with FL from 2000 to 2010 were identified and characterized by year and region of diagnosis, age (median, 65 years), gender (50% men), first-line therapy and clinical risk factors. Overall and relative survivals were estimated by calendar periods (2000-2002, 2003-2007 and 2008-2010) and region of diagnosis. With each period, first-line rituximab use and survival increased. Survival was superior in regions where rituximab was quickly adopted and inferior where slowly adopted. These differences were independent in multivariable analyses. Ten-year relative survival for patients diagnosed 2003-2010 was 92%, 83%, 78% and 64% in the age groups 18-49, 50-59, 60-69 and ⩾70, respectively. With increasing rituximab use, male sex emerged as an adverse factor. Survival improved in all patient categories, particularly in elderly women. The introduction and the establishment of rituximab have led to a nationwide improvement in FL survival. However, rituximab might be inadequately dosed in younger women and men of all ages.