Transformed Follicular Lymphoma: survival and risk retrospective analysis by the GELTAMO group

Last month in the British Journal of Haematology, the Spanish GELTAMO group reported the results of a retrospective, multi-center study on the risk of transformation, and resulting survival, of Follicular Lymphoma (FL) patients in the rituximab era.

The study, authored by Sara Alonso-Álvarez from Hospital Universitario de Salamanca-IBSAL, Salamanca, Spain, and colleagues, recruited 1,734 patients who were diagnosed between January 1, 2002 and December 31, 2012, of which 106 had histologically-documented transformation (HT) based on pathological criteria.

Highlights:

• Median age at initial diagnosis = 59 years old (16–97)
• Initial FL Grade:
  • Grade 1 = 37%
  • Grade 2 = 35%
  • Grade 3A = 16%
• Low-grade = 13%

Initial Treatment:

• Rituximab combination therapy = 65%
• Rituximab monotherapy = 5%
• 54% received an anthracycline containing regimen
• Of the 1,734 pts, CR or CRu = 75%, PR = 18%
• Ten-year OS = 72% (95% CI, 69–75) after median follow-up of 6.6-years

Transformation:

• After a median follow-up of 6.2-years 106 pts developed HT
• Median time to transformation = 2.5-years
• Cumulative index of HT (CI-HT): at 5-years = 5%, at 10-years = 8%
• Pts with HT 5-year survival following transformation = 26% (70 pts)
• Watchful waiting approach was not shown to result in significantly higher 10-year CI-HT rate compared with treatment (7.2% vs. 9.2%, P= 0.19)
• Higher 10-year CI-HT by FLIPI status (P= 0.001):
  • Low-risk = 7%
  • Intermediate-risk = 9%
  • High-risk = 14%
• No type of treatment was more significantly associated with 10-year CI-HT rates than any other
• Independent factors found to influence 5-year survival after transformation
  • Not receiving an Autologus Stem Cell Transplantation (ASCT) HR = 3.9 (95% CI: 1.5–10.1)
  • Higher-risk revised-IPI score HR = 2.2 (95% CI: 1.1–4.2)
  • No response to salvage therapy HR = 5.3 (95% CI: 2.4–12.0)
• Independent predictors of HT were high-risk FLIPI (HR 2.6, 95% CIL 1.5–4.5) and no response to initial therapy (HR 2.9, 95% CI: 1.3–6.8)

This study represents the largest data series analysing FL transformation, with a mandatory histological confirmation, and the authors conclude by stating that an “international consensus on the definition of FL transformation must be reached if we are to reliably establish the CI-HT”. To this end, the authors state that further prospective and retrospective trials will need to be conducted, due to the rarity of FL transformation, this will also help to determine the role of stem cell transplantation in the treatment of FL transformation.

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 Espanol de Linfoma y Transplante Autologo de Medula Osea, 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.