The Risk of Transformation of Follicular Lymphoma “Transformed” by Rituximab: The Aristotle Study Promoted by the European Lymphoma Institute

Abstract

Results: The expression of 395 genes was associated with the risk of progression. Twenty-three genes reflecting both B-cell biology and tumour microenvironment were retained to build a predictive model.The model identified a population at increased risk of progression in the training cohort (P < 0.001).The locked model was tested in the 3 independent validation cohorts.In the overall validation cohort, 26% of all patients (122/461) were identified as being at high risk of progression. The median PFS was 3.1 and 10.8 years in the high-and low-risk groups, respectively (p < 0.001, Figure 1). The risk of lymphoma progression at 2 years was twice higher in the high-risk group (38% versus 19%, P < 0.001).In a multivariate analysis, the score predicted PFS independently of anti-CD20 maintenance treatment and of the FLIPI score (Hazard Ratio for the combined cohort, 2.30; 95% CI, 1.72-3.08). In particular, the model stratified patients with high-risk FLIPI into groups with markedly distinct outcome (median PFS of 2.1 vs 6.6 years; log-rank test, p < 0.001).Additional unsupervised analyses of the training cohort expression data confirmed that both tumour cells and microenvironment features impacted FL prognosis. Namely, a centroblast-associated signature had adverse prognostic significance, further strengthening the biological rationale of this model. Conclusion:Using the largest study evaluating molecular prognostic biomarkers in FL patients, we developed a robust 23-gene expression-based predictor of PFS, applicable to routinely available FFPE biopsies from FL patients at diagnosis. In patients treated initially with rituximab-chemotherapy, this model identifies patients with a high risk of early progression.

Transformed follicular lymphoma in the rituximab era: A report from the Spanish Lymphoma Oncology Group

“…The rate of transformation has clearly decreased in the rituximab era as has been described in recent series with a large number of patients . HT occurrence is 2% to 3% patients per year .…”

“…The rate of transformation has clearly decreased in the rituximab era as has been described in recent series with a large number of patients. 13 HT occurrence is 2% to 3% patients per year. 2,14,15 Three studies have been performed in the era of immunochemotherapy, 7,9,14 describing that the rate of transformation was close to 10%.…”

Novel acquisitions on biology and management of transformed follicular lymphoma

“…Large retrospective series, mainly including patients treated without rituximab, documented a stable risk of HT of 2% to 3%/year through at least 10 to 15 years from diagnosis of FL and a subsequent plateau . Subsequent analysis performed during the rituximab era has shown reduced frequency of HT …”

“…5,7,8 Subsequent analysis performed during the rituximab era has shown reduced frequency of HT. 9,31 A second biopsy to confirm the HT is preferable, although not always possible due to poor clinical conditions. Some series describing the transformation into an aggressive lymphoma of FL reported cases identified by clinical features at time of disease relapse without histologic confirmation.…”

“…A risk reduction in the rituximab era (2% yearly decrease in the incidence) has been reported in the Mayo Clinic/Iowa series by Link et al 9 In a large, multicenter, retrospective survey, prior therapy with rituximab significantly reduced the frequency of HT at first relapse, this protective effect was more evident in the patients receiving maintenance therapy. 31 The largest prospective registry, the LymphoCare study, has also emphasized the protective effect from HT of rituximab maintenance 10 ; however, probably due to low number of events, rituximab maintenance was not associated to risk of HT in the PRIMA trial. 40…”