Progression-free survival at 24 months (PFS24) and subsequent outcome for patients with diffuse large B-cell lymphoma (DLBCL) in the real-world setting
Authors: H.T. van der Galiën, M. Hoogendoorn, R.E. Kibbelaar, T. van Meerten, R.S. van Rijn
Journal: Annals of Oncology (2018)

With great interest, we read the article by Maurer et al., in which the Surrogate Endpoint for Aggressive Lymphoma (SEAL) collaboration reported that diffuse large B-cell lymphoma (DLBCL) patients who are enrolled in randomized clinical trials and remain alive without progression at 24 months from the onset of treatment with the first-line anthracycline-based immuno-chemotherapy (PFS24), have excellent outcomes, with an overall survival (OS) comparable to the general population [1.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]. Using PFS24 as a surrogate end point in clinical trials compared with the classic OS may allow a faster approval of effective new drugs for hemato-oncologic patients with unmet medical needs. However, in the end, these new drugs will be applied not only to DLBCL patients in randomized clinical trials but also to a substantial amount of ‘real-world’ patients, who are excluded from trials for several reasons such as patient preference, socio-economic circumstances, distant homes, older age and comorbidities [2.Boslooper K. Kibbelaar R. Storm H. et al.Treatment with rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone is beneficial but toxic in very elderly patients with diffuse large B-cell lymphoma: a population-based cohort study on treatment, toxicity and outcome.Leuk Lymphoma. 2014; 55: 526-532Crossref PubMed Scopus (41) Google Scholar, 3.Kibbelaar R.E. Oortgiesen B.E. van der Wal-Oost A.M. et al.Bridging the gap between the randomised clinical trial world and the real world by combination of population-based registry and electronic health record data: a case study in haemato-oncology.Eur J Cancer. 2017; 86: 178-185Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar]. To answer the question how the data from the SEAL collaboration compare with ‘real-world’, we would like to report the population-based survival data from our HemoBase registry, which is a > 10-year cohort from 2005 to 2018, including all 558 patients diagnosed with DLBCL treated in the province of Friesland, The Netherlands [4.Van der Galien H.T. Kooistra H.A. Veeger N.J.G.M. et al.Outcome of a 10-year population-based cohort of diffuse large b-cell lymphoma patients in the first-line, refractory and relapsed setting: ‘Real-world’ data identify subgroups in need of new therapies [abstract].23rd Congress of European Hematology Association. 15 June 2018; : 214769Google Scholar]. In addition, as this database contains fully complete parameters, we can provide insight in causes of death after PFS24. In our cohort, 474 (85%) patients received anthracycline-containing immuno-chemotherapy. Median age was 67 years (range 18–93) and 70% of patients were >60 years, which is older than patients from the SEAL cohort (52% >60) [1.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]. Patients were 56% male, 48% had an elevated lactate dehydrogenase, 53% had stage III–IV disease and 13% had an Eastern Cooperative Oncology Group performance status of 2–4. The International Prognostic Index was 0–1 in 37%, 2 in 26%, 3 in 21% and 4–5 in 16% and comparable to the SEAL cohort. 319 patients (67%) achieved PFS24. The subsequent OS at 3, 5 and 7 years was 91.2%, 85.5% and 71.6%, respectively (Figure 1A). After PFS24, 28/319 patients (9%) had relapsed disease and 57/319 patients (18%) died. Causes of death were relapsed lymphoma (19%), cardiovascular events (23%), second malignancies (25%) and other (8%). In 25% of cases, the cause of death was unknown—the majority of these patients were >80 years old (Figure 1B). In conclusion, although patients in clinical trials differ substantially from those in the general population, OS in our ‘real-world’ cohort did not differ from OS in the SEAL cohort for PFS24 patients in the first 5 years, supporting the use of PFS24 as a surrogate end point. However, after 5 years, in comparison with clinical trial patients, there was a slight decline in survival. Even years after PFS24, fatal relapses occurred. Also, a notable number of deaths may have been related to previous DLBCL treatment with immuno-chemotherapy, e.g. cardiovascular events and second malignancies. However, these patients represent an older population with more comorbidities. Longer follow-up of the SEAL collaboration data and comparison to our cohort will give more insight into these important events for all patients. Unrestricted grant by Servier (no grant number applies).