scholarly journals Incidence and Outcome of Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL) in a Population-Based Cohort of 3165 Patients in Sweden

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2975-2975 ◽  
Author(s):  
Sara Harrysson ◽  
Sandra Eloranta ◽  
Sara Ekberg ◽  
Gunilla Enblad ◽  
Mats Jerkeman ◽  
...  

Abstract Background Our knowledge around the incidence of relapse and primary refractory disease in patients with diffuse large B-cell lymphoma (DLBCL) in the rituximab era is mostly derived from randomized controlled trials or specialized center cohorts presenting selected patient materials. With new therapies being evaluated and launched at diagnosis as well as in the relapsed/refractory setting there is a need for a better understanding of the response and outcome with current treatment strategies. Here we investigated the incidence of primary refractory DLBCL and first relapse as well as survival among patients with relapsed/refractory DLBCL in a population-based cohort. Methods Patients with a primary diagnosis of DLBCL in 2007-2014 were identified using the Swedish Lymphoma Register in 5 of 6 health care regions, and followed until October 31st 2017. Primary CNS lymphomas and primary mediastinal B-cell lymphomas were excluded. The register contains information about clinical characteristics, primary treatment, treatment response and relapse. Information regarding treatment response and progression/relapse was validated through medical chart review in all patients. Primary treatment with curative intent was defined as having started treatment with anthracycline-based chemotherapy (mostly R-CHOP). Early relapse was defined as having primary refractory disease (stable or progressive disease (SD/PD) at response evaluation) or relapse within a year from diagnosis. Overall and progression-free survival probabilities were estimated with the Kaplan-Meier method in the entire cohort and among relapsed/refractory patients by early/late relapse and by age +/- 70 years. Additionally, cumulative incidence of relapsed/refractory disease by follow-up time was shown graphically accounting for the presence of competing risks. Results In the study population of 3165 patients, median age at diagnosis was 71 years (range 18 to 97). In this unselected cohort, 80% of the patients started treatment with curative intent. Five-year overall survival (OS) for patients treated with curative intent was 78% (95% CI: 76-80) and 5-year progression free survival (PFS) was 60% (95% CI: 58-62). Patients who received non-curative intent or palliative therapy (20%) had a median OS of 4.7 months (95% CI: 3.4-5.7). The 10-year cumulative incidence of relapsed/refractory disease in patients treated with curative intent was 22% (95% CI: 20-24) and the majority relapsed within two years (n=315, 60%). Five percent of the patients starting primary treatment with curative intent, only received 1 or 2 treatment cycles and were not evaluated for response. Patients with relapsed/refractory disease had a poor prognosis. For patients with early relapse, median survival from the date of relapse was 4.6 months (95% CI: 4.1-5.7) and 5-year OS was 11% (95% CI; 8-15) whereas patients with late relapse had a median survival of 18.0 months (95% CI: 13.0-24.5) and a 5-year OS of 26% (95% CI: 20-33). Survival in younger patients (≤70 years) by early and late relapse was higher although still low; 5-year OS in early relapse was 17% (95% CI: 12-23) and in late relapse 37% (95% CI: 27-48). Among older patients (>70 years) with early relapse, 5-year OS was only 4% (95% CI: 2-9) and in patients with late relapse it was 16% (95% CI: 9-24). More information regarding treatment intensity among relapsed/refractory patients will be presented. Conclusion The 10-year cumulative incidence of relapsed/refractory disease in patients with DLBCL treated with curative intent is 22% in this population-based study, which is lower compared to previous reports. Outcome for patients with relapsed/refractory disease continues to be poor especially for patients with early progression/relapse, even among younger patients going on to intensive second-line chemotherapy aiming for autologous stem cell transplantation. These results underscore both the urgency of new therapies for relapsed/refractory DLBCL as well as the need for identification of high-risk patients already at diagnosis. Figure 1. Overall survival (OS) and progression-free survival (PFS) among 3165 patients with diffuse large B-cell lymphoma (DLBCL) diagnosed in Sweden 2007-2014 treated with curative or palliative intent, and cumulative incidence of relapsed/refractory disease and survival among 529 relapsed/refractory patients by timing of relapse (early/late) and age (+/-70 years). Figure. Figure. Disclosures Harrysson: Janssen Pharmaceuticals: Other: The Department have recieved partial funding from Janssen Pharmaceuticals. Eloranta:Janssen Pharmaceuticals: Other: S Eloranta is currently employed as a project coordinator and her salary is funded via a public-private real world evidence collaboration between Karolinska Institutet and Janssen Pharmaceuticals. Ekberg:Janssen Pharmaceuticals: Other: The department has received partial funding from Janssen Pharmaceuticals. Wahlin:Gilead: Consultancy, Honoraria, Research Funding; Roche: Research Funding. Smedby:Janssen Pharmaceuticals: Other: The Department have recieved partial funding from Janssen Pharmaceuticals.

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sara Harrysson ◽  
Sandra Eloranta ◽  
Sara Ekberg ◽  
Gunilla Enblad ◽  
Mats Jerkeman ◽  
...  

AbstractWe performed a national population-based study of all patients diagnosed with diffuse large B-cell lymphoma (DLBCL) in Sweden in 2007–2014 to assess treatment intent and risk of relapsed/refractory disease, including central nervous system (CNS) relapse, in the presence of competing risks. Overall, 84% of patients started treatment with curative intent (anthracycline-based) (n = 3550, median age 69 years), whereas 14% did not (n = 594, median age 84 years) (for 2% the intent was uncertain). Patients treated with curative intent had a 5-year OS of 65.3% (95% CI: 63.7–66.9). The median OS among non-curatively treated patients was 2.9 months. The 5-year cumulative incidence of relapsed/refractory disease in curative patients was 23.1% (95% CI: 21.7–24.6, n = 847). The 2-year cumulative incidence of CNS relapse was 3.0% (95% CI: 2.5–3.6, n = 118) overall, and 8.0% (95% CI: 6.0–10.6, n = 48) among patients with high CNS-IPI (4–6), when considering other relapse locations and death as competing events. The incidence of relapsed/refractory DLBCL overall and in the CNS was lower than in previous reports, still one in seven patients was not considered fit enough to start standard immunochemotherapy at diagnosis. These results are important for quantification of groups of DLBCL patients with poor prognosis requiring completely different types of interventions.


2013 ◽  
Vol 6 ◽  
pp. CMBD.S12713
Author(s):  
S. Mercadal ◽  
F. Climent ◽  
E. Domingo-Doménech ◽  
A. Oliveira ◽  
V. Romagosa ◽  
...  

Diffuse large b-cell lymphoma (DLBCL) is an aggressive and potentially curable lymphoma that presents itself as stage I-II in 30% of all cases. It is known that in these localized stages, 15-20% of patients treated without rituximab eventually relapse, but less data exist regarding rituximab era. We have analyzed clinico-pathological features and risk of relapse in 98 patients with I-II stage DLBCL in complete response (CR) or unconfirmed CR (CRu) after first-line treatment consisting of immunochemotherapy. Twelve patients (12.2%) eventually relapsed. Late relapse, more than two years after diagnosis, occurred in three patients, and early relapse, less than two years after diagnosis, was documented in nine patients. Median time from diagnosis to relapse was 0.61 years for patients with early relapse and 3.66 years for patients with late relapse. The second CR rate obtained was similar in the late and in early relapsing patients, being 33% versus 44% ( p = 0.072), respectively. Three-year overall survival (OS) was 22% for early relapsing patients and 33% for late relapsing patients ( p = 0.65). In conclusion, patients who are diagnosed with stage I-II DLBCL and achieve a CR/CRu with first line immunochemotherapy have a good prognosis. However, a proportion of patients relapse, and this is less frequent in patients treated with first line with immunochemotherapy. These patients have a poor prognosis.


2019 ◽  
Vol 72 (1-2) ◽  
pp. 25-29
Author(s):  
Maja Popovic ◽  
Gorana Matovina-Brko ◽  
Dragana Petrovic ◽  
Bojana Vranjkovic ◽  
Jelena Radic ◽  
...  

Introduction. The research aimed to evaluate the impact of age-adjusted international prognostic index and time to the first relapse on overall survival and progression-free survival from the beginning of the second line of treatment in patients with relapsed/ refractory diffuse large B-cell lymphoma. Material and Methods. The research included 36 patients with relapsed/refractory diffuse large B-cell lymphoma treated at the Oncology Institute of Vojvodina, Serbia, from January 2013 to December 2015. Patients were stratified according to age-adjusted international prognostic index score at the time of relapse into patients with low risk (score 0 - 1) and patients with high risk (score 2 - 3), as well as according to the time of the first relapse: early relapse (? 12 months) and late relapse (> 12 months). Results. In the group of patients with a score of 0 - 1, the median overall survival was 44 months compared with 6 months in patients with score of 2 - 3, hazard ratio 0,4 (confidence interval 0,16 - 0,99), p = 0,03. In patients with early relapse, the median overall survival was 7 months compared with 25 months in patients with late relapse, hazard ratio 0,55 (confidence interval 0,25 - 1,19), p = 0,12. In patients with early relapse, median progression-free survival was 0 months compared with 10 months in patients with late relapse, hazard ratio 0,34 (confidence interval 0,12 - 1,00), p = 0,0017. Conclusion. The impact of age-adjusted international prognostic index score significantly affects overall survival in patients with relapsed diffuse large B-cell lymphoma. The time to the first relapse impacts progression-free survival calculated from the time of the second-line treatment initiation.


2008 ◽  
Vol 26 (19) ◽  
pp. 3166-3175 ◽  
Author(s):  
Corrado Tarella ◽  
Manuela Zanni ◽  
Michele Magni ◽  
Fabio Benedetti ◽  
Caterina Patti ◽  
...  

Purpose To investigate the impact of adding rituximab to intensive chemotherapy with peripheral-blood progenitor cell (PBPC) autograft for high-risk diffuse large B-cell lymphoma (DLB-CL) and follicular lymphoma (FL). Patients and Methods Data were collected from 10 centers associated with Gruppo Italiano Terapie Innnovative nei Linfomi for 522 patients with DLB-CL and 223 patients with FL (median age, 47 years) who received the original or a modified high-dose sequential (HDS) chemotherapy regimen. HDS was delivered to 396 patients without (R−) and to 349 patients with (R+) rituximab; 154 (39%) and 178 patients (51%) in the R− and R+ subsets, respectively, underwent HDS for relapsed/refractory disease. Results A total of 355 R− (90%) and 309 R+ patients (88%) completed the final PBPC autograft. Early treatment-related mortality was 3.3% for R− and 2.8% for R+ (P = not significant). Two parameters significantly influenced the outcome: disease status at HDS, with 5-year overall survival (OS) projections of 69% versus 57% for diagnosis versus refractory/relapsed status, respectively, and rituximab addition, with 5-year OS of 69% versus 60% in the R+ versus R− groups, respectively. In the multivariate analysis, these two variables maintained an independent prognostic value. The marked benefit of rituximab was evident in patients receiving HDS as salvage treatment: the 5-year OS projections for R+ versus R− were, respectively, 64% versus 38%, for patients with refractory disease or early relapse and 71% versus 57%, for patients with late relapse, partial response, or second/third relapse. Conclusion The results of this large series indicate that rituximab should be included in the current practice of PBPC autograft for DLB-CL and FL.


Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 498-505 ◽  
Author(s):  
Jonathan W. Friedberg

Abstract Despite overall improvements in outcomes of diffuse large B-cell lymphoma (DLBCL), approximately one-third of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality. Novel insights from gene-expression analyses have increased our understanding of chemotherapy resistance and yielded rational targets for therapeutic intervention to both prevent and treat relapsed/refractory DLBCL. The clinical approach to relapsed/refractory DLBCL should include high-dose therapy and autologous stem cell transplantation (HD-ASCT) with curative intent in patients without comorbidities. Results from the recently reported CORAL study suggest that patients refractory to rituximab-containing regimens have inferior outcomes with HD-ASCT. Ongoing efforts to improve ASCT include novel conditioning regimens and evaluation of maintenance approaches after ASCT. Unfortunately, because the majority of patients are not eligible for ASCT due to refractory disease or age/comorbidities, these approaches have limited impact. The large group of patients not eligible for ASCT have incurable disease and should be referred for clinical trials of rationally targeted agents.


Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 399-399
Author(s):  
Sara Harrysson ◽  
Sandra Eloranta ◽  
Sara Ekberg ◽  
Gunilla Enblad ◽  
Mats Jerkeman ◽  
...  

Background Diffuse large B cell lymphoma (DLBCL) is an aggressive but often curable disease. However a proportion of the patients are primary refractory or relapse (R/R DLBCL) following standard immuno-chemotherapy, which is associated with a much worse prognosis especially if the CNS is involved. Current knowledge around the incidence of R/R DLBCL is mostly derived from randomized controlled trials or specialized center cohorts presenting selected patient materials. With new available treatment options for these patients it is of great importance to accurately estimate the incidence in absolute terms. Here we investigated the incidence of R/R DLBCL overall and in the CNS in a nationwide population-based cohort accounting for the presence of competing risks. Methods Patients with a primary diagnosis of DLBCL in 2007-2014 were identified using the Swedish Lymphoma Register and followed until October 31st 2017. Primary CNS lymphomas, primary mediastinal B-cell lymphomas and transformed lymphomas were excluded. The register contains information about clinical characteristics, primary treatment, treatment response and relapse. Information regarding treatment response and progression/relapse as well as site of relapse was validated through medical chart review in all patients. Primary treatment with curative intent was defined as having started treatment with anthracycline-based chemotherapy (mostly R-CHOP). Overall (OS) and progression-free survival (PFS) were estimated using the Kaplan-Meier method in the full cohort. Cumulative incidence of R/R DLBCL was estimated in the subset of patients who were treated with curative intent accounting for the competing risk of death. The net probability of CNS progression/relapse by CNS IPI was estimated in curatively treated patients who did not have CNS involvement at diagnosis. The cumulative incidence of CNS relapse was estimated non-parametrically with death and non-CNS progression/relapse as competing risks among all curatively treated patients and restricted to patients with high CNS IPI (4-6) separately. Results In the study population of 4205 patients, median age at diagnosis was 71 years (range 18 to 105). Sixteen percent of patients (n=677, median age 83 years) were not able to start treatment with curative intent, with the median OS in this group of only 2.7 months. Two-year OS for patients treated with curative intent was 88% (95% CI: 87-89) and 2-year progression free survival (PFS) was 70% (95% CI: 69-72) (fig 1a). The 5-year cumulative incidence of relapsed/refractory disease in patients treated with curative intent was 23% (95% CI: 22-24, total N=713) (fig 1b) and the majority relapsed within two years (n=646, 77%). Five percent of the patients starting primary treatment with curative intent, only received 1 or 2 treatment cycles and were not evaluated for response. The 2-year cumulative incidence of CNS relapse in curatively treated patients was 2.8% (95% CI: 2.7-3.4, total N=126) (fig 1b). For patients with high CNS IPI (4-6) the 2-year rate of CNS relapse was 12% (95% CI: 8-16) when estimated using the Kaplan-Meier method (fig 1c), but only 8% (95% CI: 6-11) in the cumulative incidence model (fig 1d) accounting for other relapses and death as competing events. Conclusion The 5-year cumulative incidence of relapsed/refractory disease in patients with DLBCL treated with curative intent is 23% in this population-based study, which is lower than in previously published reports. Overall, 16% of patients were not able to start primary curative intent treatment, representing an older group of patients with a dismal OS. An additional 5% of patients were not able to tolerate more than 1-2 cycles, defining another group of patients with unmet medical needs. The 2-year cumulative incidence of CNS relapse is <10% even in high-risk patients when estimating absolute risk in the real world where patients also face risks of non-CNS relapse and death. Figure 1 A): Overall survival (OS) and progression-free survival (PFS) among 4205 patients with diffuse large B-cell lymphoma (DLBCL) diagnosed in Sweden 2007-2014 treated with curative (n=3528 ) or palliative intent (n=677). B): Cumulative incidence of CNS relapse in the presence of competing risks of death and non-CNS relapse. C): Net probability of CNS relapse by CNS IPI (N=3499). D): Cumulative incidence of CNS relapse restricted to 414 patients with high CNS IPI (4-6). Disclosures Harrysson: Janssen pharmaceuticals: Other: This project was partly funded through a private-public collaboration between KI and Janssen pharmaceuticals.; Swedish Cancer Society: Other: This project was partly funded by the Swedish Cancer Society.. Eloranta:Karolinska Institutet: Other: coordinator for a public-private real world evidence; Janssen Pharmaceuticals.: Other: project coordinator for a public-private real world evidence. Ekberg:Janssen Pharmaceuticals: Other: This project was partly funded through a private-public collaboration between KI and Janssen pharmaceuticals.; Swedish Cancer Society: Other: This project was partly funded by the Swedish Cancer Society. Enblad:Kite/Gilead: Membership on an entity's Board of Directors or advisory committees. Jerkeman:Janssen: Honoraria, Research Funding; Gilead: Honoraria, Research Funding; Acerta: Honoraria, Research Funding; Celgene: Honoraria, Research Funding; Roche: Honoraria, Research Funding. Wahlin:Roche and Gilead: Consultancy. Andersson:Gilead, Janssen and Roche: Consultancy; Gilead: Research Funding; Abbvie and Janssen: Membership on an entity's Board of Directors or advisory committees. Smedby:Janssen Pharmaceuticals: Other: This project was partly funded through a private-public collaboration between KI and Janssen pharmaceuticals.; Takeda: Research Funding; Celgene: Honoraria.


Blood ◽  
2020 ◽  
Vol 136 (24) ◽  
pp. 2803-2811
Author(s):  
Anna R. Hayden ◽  
Petter Tonseth ◽  
Derrick G. Lee ◽  
Diego Villa ◽  
Alina S. Gerrie ◽  
...  

Abstract Cure rates for primary mediastinal large B-cell lymphoma (PMBCL) have improved with the integration of rituximab. However, the type of primary therapy and role of radiotherapy (RT) remains ill-defined. Herein, we evaluated the outcome of PMBCL primarily treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and the impact of an end-of-treatment (EOT) 18F-fluorodeoxyglucose positron emission tomography (PET) scan to guide consolidative RT. Patients ≥18 years of age with PMBCL treated with curative intent rituximab-chemotherapy were identified. Prior to 2005, patients were recommended to receive R-CHOP + RT (RT era). Beginning in 2005, EOT PET was used to guide RT and only those with a PET-positive scan received RT (PET era). In total, 159 patients were identified, 94% were treated with R-CHOP and 44% received RT (78% in RT era, 28% in PET era). The 5-year time to progression (TTP) and overall survival (OS) for the entire cohort were 80% and 89%, respectively, similar across treatment eras. Overall, 10% had refractory disease. In total, 113 patients had an EOT PET scan: 63% negative and 37% positive with a 5-year TTP of 90% vs 71% and 5-year OS of 97% vs 88%, respectively. For those with Deauville (D)-scored PET scans (n = 103), the 5-year TTP for PET-negative cases by Deauville criteria (D1-D3, DX) was 91%, with inferior outcomes for D5 vs D4 (5-year TTP 33% vs 87%, P = .0002). Outcomes for PMBCL treated with RCHOP are favorable and use of a PET-adapted approach reduces RT in the majority of patients. A small proportion have refractory disease and may benefit from an alternate treatment.


Author(s):  
David Morland ◽  
Ghali Zizi ◽  
François Godard ◽  
Anne-Cécile Gauchy ◽  
Carole Durot ◽  
...  

2012 ◽  
Vol 54 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Tanin Intragumtornchai ◽  
Udomsak Bunworasate ◽  
Noppadol Siritanaratkul ◽  
Archrob Khuhapinant ◽  
Weerasak Nawarawong ◽  
...  

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