Risk of, and survival following, histological transformation in follicular lymphoma in the rituximab era. A retrospective multicentre study by the Spanish GELTAMO group

Abstract

The diagnostic criteria for follicular lymphoma (FL) transformation vary among the largest series, which commonly exclude histologically-documented transformation (HT) mandatorily. The aims of this retrospective observational multicentre study by the Spanish Grupo Español de Linfoma y Transplante Autólogo de Médula Ósea, which recruited 1734 patients (800 males/934 females; median age 59 years), diagnosed with FL grades 1-3A, were, (i) the cumulative incidence of HT (CI-HT); (ii) risk factors associated with HT; and (iii) the role of treatment and response on survival following transformation (SFT). With a median follow-up of 6·2 years, 106 patients developed HT. Ten-year CI-HT was 8%. Considering these 106 patients who developed HT, median time to transformation was 2·5 years. High-risk FL International Prognostic Index [Hazard ratio (HR) 2·6, 95% confidence interval (CI): 1·5-4·5] and non-response to first-line therapy (HR 2·9, 95% CI: 1·3-6·8) were associated with HT. Seventy out of the 106 patients died (5-year SFT, 26%). Response to HT first-line therapy (HR 5·3, 95% CI: 2·4-12·0), autologous stem cell transplantation (HR 3·9, 95% CI: 1·5-10·1), and revised International Prognostic Index (HR 2·2, 95% CI: 1·1-4·2) were significantly associated with SFT. Response to treatment and HT were the variables most significantly associated with survival in the rituximab era. Better therapies are needed to improve response. Inclusion of HT in clinical trials with new agents is mandatory.

Patterns of change in treatment, response, and outcome in patients with follicular lymphoma over the last four decades: a single-center experience

“…Despite a median OS now approaching 20 years, early progression (progression of disease within 24 months, or POD24), defined as a relapse within the first 2 years of frontline treatment, confers a much poorer prognosis 16 . Likewise, histologic transformation (HT) to a high-grade lymphoma significantly reduces survival 17,18 , although recent studies have suggested that its incidence might be lower in the rituximab era 19 . Some single-center and registry studies have described the changes in survival of FL patients over the last decades and trends in relative survival according to the general population 7,9 .…”

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

“…5 The current rate of HT stands at 10%. 6,7 The importance of studying HT relies in the fact that while the clinical course of FL tends to be indolent for decades, when an HT occurs, the expected survival may decrease to approximately 2 years. 8,9 Although this process was first described more than 70 years ago by Gall and Mallory, 10 its biological process and clinical events remain unknown.…”

Autologous stem cell transplantation may be curative for patients with follicular lymphoma with early therapy failure who reach complete response after rescue treatment

“…However, FL remains largely incurable, relapses remain common, and patients tend to become chemorefractory and achieve less durable and lower‐quality responses after subsequent therapies . Moreover, transformation may occur, and many patients ultimately die from the disease . In patients requiring treatment, the addition of rituximab to conventional chemotherapy was a significant development in FL therapy, with several phase III randomized trials demonstrating the benefits, including better OS, of first‐line rituximab‐containing chemotherapy .…”