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Impact of allogeneic stem cell transplantation comorbidity indexes after haplotransplant using post-transplant cyclophosphamide
Jullien, M., Orvain, C., Berceanu, A., Couturier, M. A., Guillaume, T., Peterlin, P., Garnier, A., Le Bourgeois, A., Klemencie, M., Schmidt, A., et al
Cancer medicine. 2021
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Editor's Choice
Abstract
BACKGROUND Three different scoring systems have been developed to assess pre-transplant comorbidity in allogeneic hematopoietic stem cell transplantation (Allo-HSCT): the Hematopoietic Cell Transplantation-Specific Comorbidity Index, the Comorbidity/Age index, and the Augmented Comorbidity/Age index. All were devised to predict overall survival (OS) and disease-free survival (DFS) survivals and non-relapse mortality (NRM) in patients receiving HLA-matched Allo-HSCT, but their performance has scarcely been studied in the haploidentical Allo-HSCT setting with post-transplant cyclophosphamide, a procedure in constant expansion worldwide. METHODS To address this issue, their impact on survivals and NRM was examined in a cohort of 223 patients treated with haploidentical Allo-HSCT in four different centers. RESULTS With a median follow-up of 35.6 months, 3-year OS, DFS, and NRM were 48.1% ± 4%, 46.3% ± 4%, and 30.0% ± 3%, respectively. No impact was found for any of the three comorbidity scores in univariate analysis. In multivariate analyses, the only three factors associated with lower OS were DRI (p < 0.001), an older age of recipients (=55 years old, p = 0.02) and of donors (=40 years old, p = 0.005). Older donor age was also associated with lower DFS and higher NRM. CONCLUSION The comorbidity scores do not predict survivals nor NRM in haploidentical Allo-HSCT with PTCY, suggesting that pre-transplant comorbidities should not be a contra-indication to this procedure.
PICO Summary
Population
Patients from four European centres who underwent haploidentical transplantation with post-transplant cyclophosphamide (n=223)
Intervention
Use of three comorbidity scores for each patient: 1) Hematopoietic Cell Transplantation-Specific Comorbidity Index
Comparison
2) Comorbidity/Age index, and 3) the Augmented Comorbidity/Age index
Outcome
With a median follow-up of 35.6 months, 3-year overall survival (OS), disease free survival (DFS), and non-relapse mortality (NRM) were 48.1% ± 4%, 46.3% ± 4%, and 30.0% ± 3%, respectively. No impact was found for any of the three comorbidity scores in univariate analysis. In multivariate analyses, the only three factors associated with lower OS were disease risk index, an older age of recipients (>/=55 years old) and of donors (>/=40 years old). Older donor age was also associated with lower DFS and higher NRM.
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Second-Line Tisagenlecleucel or Standard Care in Aggressive B-Cell Lymphoma
Bishop, M. R., Dickinson, M., Purtill, D., Barba, P., Santoro, A., Hamad, N., Kato, K., Sureda, A., Greil, R., Thieblemont, C., et al
The New England journal of medicine. 2021
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Editor's Choice
Abstract
BACKGROUND Patient outcomes are poor for aggressive B-cell non-Hodgkin's lymphomas not responding to or progressing within 12 months after first-line therapy. Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for diffuse large B-cell lymphoma after at least two treatment lines. METHODS We conducted an international phase 3 trial involving patients with aggressive lymphoma that was refractory to or progressing within 12 months after first-line therapy. Patients were randomly assigned to receive tisagenlecleucel with optional bridging therapy (tisagenlecleucel group) or salvage chemotherapy and autologous hematopoietic stem-cell transplantation (HSCT) (standard-care group). The primary end point was event-free survival, defined as the time from randomization to stable or progressive disease at or after the week 12 assessment or death. Crossover to receive tisagenlecleucel was allowed if a defined event occurred at or after the week 12 assessment. Other end points included response and safety. RESULTS A total of 322 patients underwent randomization. At baseline, the percentage of patients with high-grade lymphomas was higher in the tisagenlecleucel group than in the standard-care group (24.1% vs. 16.9%), as was the percentage with an International Prognostic Index score (range, 0 to 5, with higher scores indicating a worse prognosis) of 2 or higher (65.4% vs. 57.5%). A total of 95.7% of the patients in the tisagenlecleucel group received tisagenlecleucel; 32.5% of the patients in the standard-care group received autologous HSCT. The median time from leukapheresis to tisagenlecleucel infusion was 52 days. A total of 25.9% of the patients in the tisagenlecleucel group had lymphoma progression at week 6, as compared with 13.8% of those in the standard-care group. The median event-free survival in both groups was 3.0 months (hazard ratio for event or death in the tisagenlecleucel group, 1.07; 95% confidence interval, 0.82 to 1.40; P?=?0.61). A response occurred in 46.3% of the patients in the tisagenlecleucel group and in 42.5% in the standard-care group. Ten patients in the tisagenlecleucel group and 13 in the standard-care group died from adverse events. CONCLUSIONS Tisagenlecleucel was not superior to standard salvage therapy in this trial. Additional studies are needed to assess which patients may obtain the most benefit from each approach. (Funded by Novartis; BELINDA ClinicalTrials.gov number, NCT03570892.).
PICO Summary
Population
Patients with aggressive lymphoma refractory to progressing within 12 months after first line therapy, identified from 65 centres in 18 countries (n=322)
Intervention
Tisagenlecleucel with optional bridging therapy (tisagenlecleucel group, n=162)
Comparison
Salvage chemotherapy and autologous hematopoietic stem-cell transplantation (standard-care group, n=160).
Outcome
A total of 95.7% of the patients in the tisagenlecleucel group received tisagenlecleucel; 32.5% of the patients in the standard-care group received autologous HSCT. The median time from leukapheresis to tisagenlecleucel infusion was 52 days. A total of 25.9% of the patients in the tisagenlecleucel group had lymphoma progression at week 6, as compared with 13.8% of those in the standard-care group. The median event-free survival in both groups was 3.0 months (hazard ratio for event or death in the tisagenlecleucel group, 1.07; 95% confidence interval, 0.82 to 1.40). A response occurred in 46.3% of the patients in the tisagenlecleucel group and in 42.5% in the standard-care group. Ten patients in the tisagenlecleucel group and 13 in the standard-care group died from adverse events.