Physician
Thomas Stauffer Larsen
Department of hematology,
| Projekt styring | ||
| Projekt status | Open | |
| Data indsamlingsdatoer | ||
| Start | 13.09.2024 | |
| Slut | 01.09.2026 | |
Allogeneic Stem Cell transplant in Relapsed/Refractory Diffuse Large B-Cell Lymphoma- A Population based Intent- to- Transplant Outcome Analysis
Short summary
The main objectives for this study are as follows. Describe characteristics (demographic and clinical) as well as treatment patterns and donor source in a Danish population of DLBCL patients with R/R disease intended for alloSCT. And describe outcomes including progression-free survival (PFS) and overall survival (OS) in R/R DLB intended for alloSCT by intention to treat and in patients receiving alloSCT.
Rationale
Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of all non-Hodgkin's Lymphoma (NHL) found in adults in the Western World. The annual incidence of NHL is estimated at 19.5 per 100,000 person years in the United States and 11.1 per 100,000 person years in Europe . The standard of care frontline treatment for DLBCL is a chemo-immunotherapy regimen consisting 6 courses of Rituximab[R], Cyclophosphamide[C], doxorubicin [H], vincristine [O], and prednisone[P] (R-CHOP). More than half of the patients that receive R-CHOP are cured; however, some patients will either be refractory to frontline therapy or relapse (R/R) after achieving remission. Second line treatments include salvage chemotherapy followed by high-dose therapy with autologous stem cell transplantation (ASCT) for eligible patients. Less than half of R/R DLBCL patients are eligible for ASCT due to high age or co-morbidities, and less than half of those eligible will be cured. Patients who are refractory to first line and/or salvage therapy or who relapse ≤12 months following ASCT have a very poor prognosis. The overall response and complete remission rates on the next line of therapy are as low as 26% and 7% respectively, with a median overall survival of 6.3 months. For patients ineligible for ASCT the outcomes are even worse. Allogeneic hematopoietic cell transplantation (alloSCT) is an effective immunotherapy for various lymphoma subtypes including DLBCL and is recognized as a standard treatment option with true curative potential in a small subset of patients ineligible for ASCT and post ASCT relapse. Long-term progression free survival (PFS) and overall survival (OS) can be obtained in the range 30-50 %. However, non-relapse morbidity and mortality in the range of 20-30% at three years despite using non-myeloablative (NMA) conditioning, hampering utility. Besides donor availability, either sibling or matched unrelated donor (MUD), immune-chemo sensitive disease is another prerequisite to be fulfilled as low burden residual disease needs to be achieved before entering transplant. In many cases relapsed DLBCL in 3rd line and beyond are refractory to traditional immune-chemotherapy and intended alloSCT consolidation is abandoned and patients enter best supportive care (BSC). Within recent years novel agents, including polatuzumab-vedotin, loncastuximab-tesirine, tafasitamab and selinexor for R/R DLBCL have been approved. These agents and regimens may add to opportunities to induce remissions allowing alloSCT. Most groundbreaking though, is the introduction of autologous chimeric antigen receptor CD19 (CAR) T-cell therapies including chimeric antigen receptor CD19 (CAR) T-cell therapies in the 3rd line setting, which is now the preferred and recommended treatment approach in R/R DLBCL in third line and beyond setting. Most recently CAR-T treatment has also proven to provide better outcomes also in the second line setting compared to standard of care high-dose chemotherapy with ASCT. Implementation of CAR-T has caused a remarkable decline in the use of alloSCT. However, access to CAR-T is limited due to significant barriers such as high cost, re-imbursement, manufacturing turnaround time, need for travel and/or hospitalization and R/R DLBCL patients continue to present an unmet medical need. In Denmark CAR-T treatment is only re-imbursed for second line treatment. For a large majority, treatment strategies are palliative with decisions being informed by prior chemotherapy exposure, co-morbidities, and patient preferences. The role and place of alloSCT in modern treatment algorithms for R/R DLBCL is undoubtedly changing these years but still has a role in regions with low or no CAR T access, in patients who may not be CAR-T candidates, patients with relapse post CAT-T therapy or patients with concomitant myelodysplasia. The graft versus lymphoma effect and long-term disease control and potential cure is indisputable, but the true benefits are biased by uncontrolled retrospective studies and limited to patients who actually received an allograft. Accordingly, patients with refractory DLBCL are not included in those series as they progress and ultimately die during attempts to achieve disease control for allowing transplant eligibility and only a small minority of patients receive alloSCT in late treatment lines due to difficulties obtaining remission and/or finding a donor. In this study using registry data we want to analyze the outcomes of all R/R DLBCL patients subject to intend of delivering an allograft.
Description of the cohort
Adult patients with DLBCL diagnosed between 01-JAN-2004 and 31-12-2021 will be identified from The Danish Lymphoma Registry (LYFO)
Data and biological material
Data from the patient journal and national registries/The Danish lymphoma registry (Lyfo)
Collaborating researchers and departments
Department of Immunology, Rigshospitalet. Department of Immunulogy, Aarhus University Hospital. Department of Hematology, Rigshospitalet. Department of Hematoogy, Aarhus University Hospital. Department of Hematology,