Trends in the Use of Hematopoietic Stem Cell Transplantation in the Management of Relapsed/Refractory Diffuse Large B Cell Lymphoma. a Retrospective Analysis of the Lymphoma Working Party of the EBMT

Field: Medicine (Health Sciences)

Background. Both autologous (auto-HSCT) and allogeneic stem cell transplantation (allo-HSCT) represent accepted treatment strategies for patients with relapsed / refractory (RR) diffuse large B cell lymphoma (DLBCL). Nevertheless, both transplant modalities have evolved over time and the advent of new drugs might have modified indications and timing of HSCT. Aims. We analyzed the transplant activity for patients with RR DLBCL reported to the EBMT registry over the last three decades. Methods. Patients were included if they had RR (primary refractory or relapsed disease) DLBCL, were above 18 years of age and had undergone auto-HSCT as 1st HSCT or allo-HSCT either as a 1st HSCT or after a prior auto-HSCT between January 1990 to December 2019. Minimal essential data-A were retrieved from the EBMT database. Results. 5454 patients [4329 auto-HSCT and 1125 allo-HSCT (556 1st allo-HSCT and 569 allo-HSCT after an auto-HSCT)] were registered in the EBMT database during the study period. The number of auto-HSCT steadily increased from 284 in the 1990-2000 period up to a maximum of 1751 in the 2015-2019 time period; the number of allo-HSCT also increased from 65 up to a peak of 585 in the same time periods. With regards to autologous recipients, there was a significant increase in age at HSCT [48.8 yrs (1990-2000) vs 57 yrs (2015-2019), p<0.0001], time between diagnosis and HSCT became shorter [17.7 mo (1990-2000) vs 14 mo (2015-2019), p<0.0001], performance status at HSCT improved (>=80% [86 (1990-2000) vs 92 (2015-2019), p<0.02], peripheral blood (PB) has become the universally used stem cell source [87% (1990-200] vs 99% (2015-2019), p<0.0001] and total body irradiation has almost been abandoned [12.9% (1990-2000) vs 0.4% (2015-2019), p<0.0001]. A significantly higher proportion of patients have undergone the autologous procedure in complete remission (CR) [19% (1990-200] vs 40% (2015-2019), p<0.0001]. 36-mo overall survival (OS) has significantly improved over time [48.3% (1990-2000) vs 57.8% (2015-2019), p=0.003] as well as non-relapse mortality (NRM) [7.3% (1990-12000) vs 5.9% (2015-2019), p=0.04]. Time between diagnosis and HSCT has decreased over time also in allogeneic recipients [25.5 mo (1990-2000) vs 19.2 mo (2015-2019), p<0.01]]. PB has become the universal source of stem cells [43% (1990-2000) vs 92% (2015-2019), p<0.0001], and there has been a more frequent use of reduced intensity conditioning protocols [43% (1990-2000) vs 63% (2015-2019), p<0.0001] as well as of matched unrelated donors and haploidentical donors [21% (1990-2000) vs 49% (2015-2019) and 0% (1990-2000) vs 19.5% (2015-2019), respectively, p<0.0001]. 36-month OS estimates have also improved [33.0% (1990-2000) vs 43.9% (2015-2019), p<0.08)] as well as those for progression free survival [28.1% (1990-2000) vs 38.6% (2015-2019), p=0.01], with no changes in NRM [31.3% (1990- 2000) vs 22% (2015-2019), p=0.44]. Summary/Conclusion. Transplantation activity, the clinical pattern of patients undergoing this treatment and the characteristics of the procedure have significantly changed over the study period; long-term outcome has significantly improved both in auto-HCT and allo-HCT recipients. Improvement of supportive measures as well as in the experience of the transplant centers and a better selection of patients could account for these changes. The introduction of new cellular therapy modalities (CART cells) initially as third line or more therapy and later on as second line therapy in patients with primary refractory or early relapsed DLBCL has already started to modify this therapeutic landscape.