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The clinical dilemma of grade 3 follicular lymphoma
Annals of Oncology Advance Access published August 26, 2016
Annals of Oncology 00: 1–1, 2016
The clinical dilemma of grade 3 follicular lymphoma
M. Sorigue1*, J. M. Ribera2 & J. M. Sancho2 1
Department of Hematology, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona; 2Department of Clinical Hematology, ICO-Hospital Germans Trias i Pujol, Jose Carreras Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain (*E-mail: [email protected])
funding None declared.
disclosure The authors have declared no conflicts of interest.
references 1. Koch K, Hoster E, Ziepert M et al. Clinical, pathological and genetic features of follicular lymphoma grade 3A: a joint analysis of the German low-grade and highgrade lymphoma study groups GLSG and DSHNHL. Ann Oncol 2016; 27: 1323–1329. 2. Horn H, Schmelter C, Leich E et al. Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles. Haematologica 2011; 96: 1327–1334. 3. Piccaluga PP, Califano A, Klein U et al. Gene expression analysis provides a potential rationale for revising the histological grading of follicular lymphomas. Haematologica 2008; 93: 1033–1038. 4. Shustik J, Quinn M, Connors JM et al. Follicular non-Hodgkin lymphoma grades 3A and 3B have a similar outcome and appear incurable with anthracycline-based therapy. Ann Oncol 2011; 22: 1164–1169. 5. Wahlin BE, Yri OE, Kimby E et al. Clinical significance of the WHO grades of follicular lymphoma in a population-based cohort of 505 patients with long follow-up times. Br J Haematol 2012; 156: 225–233.
doi: 10.1093/annonc/mdw284
© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from http://annonc.oxfordjournals.org/ at United Arab Emirates University on September 1, 2016
In a recent article, Koch et al. [1] described the histopathological and clinical features of grade 3 follicular lymphoma (FL3) patients from several German clinical trials. They found that FL3A often coexists with grades 1 and 2 FL (FL1/2) and that, unexpectedly, the survival curve of pure FL3A patients (without coexistence of FL1/2) forms a plateau, a finding previously reported for FL3B but not for FL3A. This seems to be because patients with coexisting FL1/2 and FL3A, unlike those with exclusive FL3A, relapse frequently. With the available evidence, FL3A seems biologically closer to FL1/2, while FL3B seems to be a distinct entity, although its relationship with diffuse large B-cell lymphoma (DLBCL) is unclear [2, 3]. Yet these biological differences have mostly failed to translate into consistently different clinical courses [1, 4, 5], although the lack of agreement between pathologists, the frequent morphologic heterogeneity within the same biopsy, with coexisting DLBCL or FL1/2 components, the different treatments employed ( particularly the addition of rituximab), as well as potentially insufficient follow-up make the results of these series hard to compare. Most crucially, however, the question of whether all FL3, only FL3B, or neither, are curable or follow a continuous pattern of relapses, remains open. The three recent largest series have shown different results; Shustik et al. [4] found no plateau in the survival curves of neither FL3A nor FL3B patients, while Wahlin et al. [5] found a worse overall survival but with a plateau in the survival curve of FL3B patients. On the other hand, Kock et al. [1] found that patients with pure FL3A had a prognosis similar to those with FL3B, with a plateau in both survival curves. These conflictive results are reflected in recommendations by different scientific organizations; while the ESMO and Spanish FL guidelines suggest that only FL3B patients should be treated according to DLBCL guidelines, the NCCN and Chinese guidelines suggest that this be applied to all FL3 patients. Regardless of the biological questions, this prognostic uncertainty leads to an important practical point that needs resolution. While the best and almost the only choice for cure in DLBCL resides in the first line, FL is not curable and requires long-term planning and consideration of toxicities and possible future treatments, and therefore, the therapeutic approach is different. Currently, despite a lack of strong evidence (as FL3 is
rare and often excluded from clinical trials), consensus-based use of RCHOP for FL3 (or FL3B) patients is reasonable because this regimen is the first choice for most DLBCL as well as one of the best available choices for FL. However, new drugs are becoming available and, while most of them are active in both DLBCL and FL, the benefits in first line will probably differ, especially if the treatment of choice in DLBCL depends on the molecular subtype. Therefore, it is very likely that in a few years, the lack of evidence concerning the best front-line treatment for FL3 will make more complex the decision of how to treat these patients.
letter to the editor
letter to the editor
Annals of Oncology 00: 1–1, 2016
The clinical dilemma of grade 3 follicular lymphoma
M. Sorigue1*, J. M. Ribera2 & J. M. Sancho2 1
Department of Hematology, Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona; 2Department of Clinical Hematology, ICO-Hospital Germans Trias i Pujol, Jose Carreras Research Institute, Universitat Autònoma de Barcelona, Badalona, Spain (*E-mail: [email protected])
funding None declared.
disclosure The authors have declared no conflicts of interest.
references 1. Koch K, Hoster E, Ziepert M et al. Clinical, pathological and genetic features of follicular lymphoma grade 3A: a joint analysis of the German low-grade and highgrade lymphoma study groups GLSG and DSHNHL. Ann Oncol 2016; 27: 1323–1329. 2. Horn H, Schmelter C, Leich E et al. Follicular lymphoma grade 3B is a distinct neoplasm according to cytogenetic and immunohistochemical profiles. Haematologica 2011; 96: 1327–1334. 3. Piccaluga PP, Califano A, Klein U et al. Gene expression analysis provides a potential rationale for revising the histological grading of follicular lymphomas. Haematologica 2008; 93: 1033–1038. 4. Shustik J, Quinn M, Connors JM et al. Follicular non-Hodgkin lymphoma grades 3A and 3B have a similar outcome and appear incurable with anthracycline-based therapy. Ann Oncol 2011; 22: 1164–1169. 5. Wahlin BE, Yri OE, Kimby E et al. Clinical significance of the WHO grades of follicular lymphoma in a population-based cohort of 505 patients with long follow-up times. Br J Haematol 2012; 156: 225–233.
doi: 10.1093/annonc/mdw284
© The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].
Downloaded from http://annonc.oxfordjournals.org/ at United Arab Emirates University on September 1, 2016
In a recent article, Koch et al. [1] described the histopathological and clinical features of grade 3 follicular lymphoma (FL3) patients from several German clinical trials. They found that FL3A often coexists with grades 1 and 2 FL (FL1/2) and that, unexpectedly, the survival curve of pure FL3A patients (without coexistence of FL1/2) forms a plateau, a finding previously reported for FL3B but not for FL3A. This seems to be because patients with coexisting FL1/2 and FL3A, unlike those with exclusive FL3A, relapse frequently. With the available evidence, FL3A seems biologically closer to FL1/2, while FL3B seems to be a distinct entity, although its relationship with diffuse large B-cell lymphoma (DLBCL) is unclear [2, 3]. Yet these biological differences have mostly failed to translate into consistently different clinical courses [1, 4, 5], although the lack of agreement between pathologists, the frequent morphologic heterogeneity within the same biopsy, with coexisting DLBCL or FL1/2 components, the different treatments employed ( particularly the addition of rituximab), as well as potentially insufficient follow-up make the results of these series hard to compare. Most crucially, however, the question of whether all FL3, only FL3B, or neither, are curable or follow a continuous pattern of relapses, remains open. The three recent largest series have shown different results; Shustik et al. [4] found no plateau in the survival curves of neither FL3A nor FL3B patients, while Wahlin et al. [5] found a worse overall survival but with a plateau in the survival curve of FL3B patients. On the other hand, Kock et al. [1] found that patients with pure FL3A had a prognosis similar to those with FL3B, with a plateau in both survival curves. These conflictive results are reflected in recommendations by different scientific organizations; while the ESMO and Spanish FL guidelines suggest that only FL3B patients should be treated according to DLBCL guidelines, the NCCN and Chinese guidelines suggest that this be applied to all FL3 patients. Regardless of the biological questions, this prognostic uncertainty leads to an important practical point that needs resolution. While the best and almost the only choice for cure in DLBCL resides in the first line, FL is not curable and requires long-term planning and consideration of toxicities and possible future treatments, and therefore, the therapeutic approach is different. Currently, despite a lack of strong evidence (as FL3 is
rare and often excluded from clinical trials), consensus-based use of RCHOP for FL3 (or FL3B) patients is reasonable because this regimen is the first choice for most DLBCL as well as one of the best available choices for FL. However, new drugs are becoming available and, while most of them are active in both DLBCL and FL, the benefits in first line will probably differ, especially if the treatment of choice in DLBCL depends on the molecular subtype. Therefore, it is very likely that in a few years, the lack of evidence concerning the best front-line treatment for FL3 will make more complex the decision of how to treat these patients.
letter to the editor
letter to the editor