Reply to the letter to the editor ‘Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) in the real-world setting’ by van der Galiën et al.
Authors: M.J. Maurer, T.M. Habermann
Journal: Annals of Oncology (2018)

We thank van der Galien et al. for their interest in this topic and sharing their insights from their data and experience [1.van der Galiën H.T. Hoogendoorn M. Kibbelaar R.E. et al.Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) in the real-world setting.Ann Oncol. 2019; 30: 151-152Abstract Full Text Full Text PDF PubMed Scopus (5) Google Scholar]. It is valuable to contrast real-world results with cohort of patients from clinical trials [2.Maurer M.J. Habermann T.M. Shi Q. et al.Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) enrolled on randomized clinical trials.Ann Oncol. 2018; 29: 1822-1827Abstract Full Text Full Text PDF PubMed Scopus (44) Google Scholar]. The results observed in their cohort of patients from Friesland in the Netherlands correspond with other published registry-based [3.Maurer M.J. Ghesquières H. Jais J.-P. et al.Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.J Clin Oncol. 2014; 32: 1066-1073Crossref PubMed Scopus (247) Google Scholar], trial-based [3.Maurer M.J. Ghesquières H. Jais J.-P. et al.Event-free survival at 24 months is a robust end point for disease-related outcome in diffuse large B-cell lymphoma treated with immunochemotherapy.J Clin Oncol. 2014; 32: 1066-1073Crossref PubMed Scopus (247) Google Scholar], and population-based [4.Jakobsen L.H. Bøgsted M. Brown P.D.N. et al.Minimal loss of lifetime for patients with diffuse large B-cell lymphoma in remission and event free 24 months after treatment: a Danish population-based study.J Clin Oncol. 2017; 35: 778-784Crossref PubMed Scopus (58) Google Scholar, 5.Ekberg S. Jerkeman M. Andersson P.-O. et al.Long-term survival and loss in expectancy of life in a population-based cohort of 7114 patients with diffuse large B-cell lymphoma.Am J Hematol. 2018; 93: 1020-1028Crossref Scopus (19) Google Scholar] cohorts. Combined, these results have now examined outcomes after achieving 24 months of progression-free survival (PFS24), event-free survival (EFS24) or overall survival (OS24) in over 16 000 newly diagnosed patients in diffuse large B-cell lymphoma (DLBCL) in the immunochemotherapy era. These studies consistently show a small but clinically negligible survival reduction from the background population in the first 5 years after achieving the 24-month end point. This broad confirmation across real-world and trial-based cohorts provides strong evidence for utilization of these results in patient counseling and re-prognostication of outcomes in the setting of DLBCL. The use of EFS24 or PFS24 can also be utilized as an end point in biological studies of newly diagnosed DLBCL. Initial work from the SEAL group suggests that PFS24 has promise for meeting criteria for surrogacy for OS in newly diagnosed DLBCL [6.Shi Q. Schmitz N. Ou F.-S. et al.Progression-free survival as a surrogate end point for overall survival in first-line diffuse large B-cell lymphoma: an individual patient–level analysis of multiple randomized trials (SEAL).J Clin Oncol. 2018; 36: 2593-2602Crossref PubMed Scopus (51) Google Scholar]. We agree with the authors that a potential decline in late survival compared with the background population cannot be ruled out in patients achieving EFS24 or PFS24. Indeed, this effect has been noted by Jakobsen et al. in their study from a Danish population-based series [4.Jakobsen L.H. Bøgsted M. Brown P.D.N. et al.Minimal loss of lifetime for patients with diffuse large B-cell lymphoma in remission and event free 24 months after treatment: a Danish population-based study.J Clin Oncol. 2017; 35: 778-784Crossref PubMed Scopus (58) Google Scholar]. As these cohorts continue to accrue follow-up in the immunochemotherapy era, exploration of the rate of late relapses and the magnitude and potential causes of any long-term survival deficit in EFS24/PFS24 achievers is warranted. Survivorship issues will be an important clinical concern in these patients and should be an area of future research. In addition, as PFS24 or EFS24 end points potentially move into frontline clinical trials, it will be important to continue to acquire long-term follow-up on clinical trial patients to assess for potential late effects. The National Institutes of Health University of Iowa/Mayo Clinic Lymphoma SPORE (CA97274) grant provided support for MJM and TMH.