TY - JOUR
T1 - Rituximab and the risk of transformation of follicular lymphoma: a retrospective pooled analysis
AU - Aristotle Consortium
AU - Federico, Massimo
AU - Caballero Barrigón, María Dolores
AU - Marcheselli, Luigi
AU - Tarantino, Vittoria
AU - Manni, Martina
AU - Sarkozy, Clementine
AU - Alonso-Álvarez, Sara
AU - Wondergem, Marielle
AU - Cartron, Guillaume
AU - Lopez-Guillermo, Armando
AU - Issa, Djamila
AU - Morschhauser, Franck
AU - Alcoceba, Miguel
AU - Kimby, Eva
AU - Rusconi, Chiara
AU - Chamuleau, Martine
AU - Holte, Harald
AU - Lockmer, Sandra
AU - Montoto, Silvia
AU - Gomes da Silva, Maria
AU - Aurer, Igor
AU - Zucca, Emanuele
AU - Paszkiewicz-Kozik, Ewa
AU - Minoia, Carla
AU - Skrypets, Tetiana
AU - Blaker, Yngvild Nuvin
AU - Salles, Gilles
AU - Coiffier, Bertrand
PY - 2018
Y1 - 2018
N2 - Background: Histological transformation of follicular lymphoma to aggressive lymphoma is a serious event with a substantial effect on patient outcome. The aim of the Aristotle study was to assess the effect of rituximab on the risk of histological transformation and its outcome. Methods: 11 cooperative groups or institutions across Europe contributed data to this study. Eligible patients (≥18 years) had histologically confirmed follicular lymphoma grade 1, 2, or 3a, diagnosed between Jan 2, 1997, and Dec 20, 2013. Histological transformation was defined as a biopsy-proven aggressive lymphoma that occurred as a first event after first-line therapy. The primary endpoints were the cumulative hazard of histological transformation and survival after transformation. Findings: Information was available for 10 001 patients with follicular lymphoma, 8116 of whom were eligible for analysis. 509 histological transformations were reported. After a median follow-up of 87 months (range 1–221; 2·5–97·5th percentile 5–160), the 10-year cumulative hazard of histological transformation was 7·7% (95% CI 6·9–8·5). The 10-year cumulative hazard of histological transformation was 5·2% (95% CI 4·5–6·2) in patients who received rituximab and 8·7% (7·2–10·6) in those who did not (hazard ratio [HR] 0·73, 95% CI 0·58–0·90; p=0·004). The 10-year cumulative hazard of histological transformation was 5·9% (95% CI 5·0–7·0) for patients who received induction rituximab only and 3·6% (95% CI 2·3–5·5) for those treated with induction and maintenance rituximab (HR 0·55, 95% CI 0·37–0·81; p=0·003). This finding was confirmed in a multivariate analysis (p=0·016). 287 deaths were recorded in 509 patients with histological transformation, resulting in a 10-year survival after transformation of 32% (95% CI 26–38). Survival after transformation did not differ between patients not exposed to rituximab and those who received rituximab in induction only (HR 0·94, 95% CI 0·69–1·28; p=0·70), and those who received rituximab in induction and maintenance (0·96, 0·58–1·61; p=0·88). Interpretation: The risk of histological transformation as a first event can be significantly reduced by the use of rituximab. These findings support the need to inform patients using rituximab nowadays that the risk of transformation is lower than it was before the introduction of rituxumab. Funding: Associazione Angela Serra per la Ricerca sul Cancro, European Lymphoma Institute, European Hematology Association Lymphoma Group, Fondazione Italiana Linfomi, Spanish Group of Lymphoma and Bone Marrow Transplantation.
AB - Background: Histological transformation of follicular lymphoma to aggressive lymphoma is a serious event with a substantial effect on patient outcome. The aim of the Aristotle study was to assess the effect of rituximab on the risk of histological transformation and its outcome. Methods: 11 cooperative groups or institutions across Europe contributed data to this study. Eligible patients (≥18 years) had histologically confirmed follicular lymphoma grade 1, 2, or 3a, diagnosed between Jan 2, 1997, and Dec 20, 2013. Histological transformation was defined as a biopsy-proven aggressive lymphoma that occurred as a first event after first-line therapy. The primary endpoints were the cumulative hazard of histological transformation and survival after transformation. Findings: Information was available for 10 001 patients with follicular lymphoma, 8116 of whom were eligible for analysis. 509 histological transformations were reported. After a median follow-up of 87 months (range 1–221; 2·5–97·5th percentile 5–160), the 10-year cumulative hazard of histological transformation was 7·7% (95% CI 6·9–8·5). The 10-year cumulative hazard of histological transformation was 5·2% (95% CI 4·5–6·2) in patients who received rituximab and 8·7% (7·2–10·6) in those who did not (hazard ratio [HR] 0·73, 95% CI 0·58–0·90; p=0·004). The 10-year cumulative hazard of histological transformation was 5·9% (95% CI 5·0–7·0) for patients who received induction rituximab only and 3·6% (95% CI 2·3–5·5) for those treated with induction and maintenance rituximab (HR 0·55, 95% CI 0·37–0·81; p=0·003). This finding was confirmed in a multivariate analysis (p=0·016). 287 deaths were recorded in 509 patients with histological transformation, resulting in a 10-year survival after transformation of 32% (95% CI 26–38). Survival after transformation did not differ between patients not exposed to rituximab and those who received rituximab in induction only (HR 0·94, 95% CI 0·69–1·28; p=0·70), and those who received rituximab in induction and maintenance (0·96, 0·58–1·61; p=0·88). Interpretation: The risk of histological transformation as a first event can be significantly reduced by the use of rituximab. These findings support the need to inform patients using rituximab nowadays that the risk of transformation is lower than it was before the introduction of rituxumab. Funding: Associazione Angela Serra per la Ricerca sul Cancro, European Lymphoma Institute, European Hematology Association Lymphoma Group, Fondazione Italiana Linfomi, Spanish Group of Lymphoma and Bone Marrow Transplantation.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85049322355&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/30078408
U2 - https://doi.org/10.1016/S2352-3026(18)30090-5
DO - https://doi.org/10.1016/S2352-3026(18)30090-5
M3 - Article
C2 - 30078408
SN - 2352-3026
VL - 5
SP - e359-e367
JO - The Lancet Haematology
JF - The Lancet Haematology
IS - 8
ER -