The purpose of this study was to determine whether texture analysis features present on pretreatm... more The purpose of this study was to determine whether texture analysis features present on pretreatment unenhanced computed tomography (CT) images, derived from 18F-fluorodeoxyglucose positron emission/computed tomography (18-FDG PET/CT), can predict progression-free survival (PFS), progression-free survival at 24 months (PFS 24), time to next treatment (TTNT), and overall survival in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance. Seventy-two patients with follicular lymphoma were retrospectively included. Texture analysis was performed on unenhanced CT images extracted from 18-FDG PET/CT examinations that were obtained within one month before treatment. Skewness at a fine texture scale (SSF = 2) was an independent predictor of PFS (hazard ratio = 3.72 (95% CI: 1.15, 12.11), p = 0.028), PFS 24 (hazard ratio = 13.38; 95% CI: 1.29, 138.13; p = 0.029), and TTNT (hazard ratio = 5.11; 95% CI: 1.18, 22.13; p = 0.029). Skewness v...
Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diag... more Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diagnosis. Time to lymphoma treatment (TLT) initiation can however be very heterogeneous and risk factors of progression are poorly studied. Our study evaluated 201 pts with grade 1–3a low-tumor burden FL diagnosed in four French centers between 2010 and 2020 and managed by a watch and wait strategy in real-life settings. After a median follow-up of 4.8 years, the median TLT was 4.2 years (95% confidence interval, 3.1-5.5). On multivariate analysis, elevated lactate dehydrogenase (hazard ratio [HR] = 2.2; P = 0.02), more than 4 nodal areas involved (HR = 1.7; P = 0.02) and more than 1 extranodal involvement (HR = 2.7; P = 0.01) were identified as independent predictors of TLT. The median TLT was 5.8 years for pts with no risk factor, 2.4 years for 1 risk factor, and 1.3 years for >1 risk factors (P < 0.01). In a subanalysis of 75 pts staged with positron emission tomography-computed to...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global pandemic. Phase III trials have demonstrated excellent efficacies of mRNA vaccines against SARS-CoV-2 in large population studies (Baden LR, NEJM, 2021; Polack FP, NEJM, 2020). Immunosuppressed individuals such as chronic lymphocytic leukemia (CLL) patients are at risk for a suboptimal response to 2 vaccine doses (Herishanu Y, Blood, 2021). The French National Authority for Health recommends the use of a third dose in immunosuppressed patients. However, seroconversion rate after the triple-dose vaccine is not yet known. The objective of our study was to evaluate SARS-CoV-2 antibody responses after the first, second and third doses of the BNT162b2 and mRNA-1273 vaccines. Data were collected from 17 French Innovative Leukemia Organization (FILO) investigating centers and the French CLL patients' association (SILLC). SARS-CoV-2 IgG anti-Spike levels were measured at 4-6 weeks after eac...
Introduction. In follicular lymphoma (FL), no prognostic index has been built based on a cohort o... more Introduction. In follicular lymphoma (FL), no prognostic index has been built based on a cohort of patients treated only with initial immunochemotherapy. Given the emergence of new biomolecular and metabolic prognostic factors in FL, an easy-to-compute and reliable scoring system utilizing such variables could aid in trial stratification and routine clinical evaluation. Methods. The primary endpoint for model building was progression-free survival (PFS). For discovery, we used the large prospective PRIMA trial cohort of 1,135 patients treated with initial R-chemotherapy +/- R-maintenance. Variables considered for model building included age, sex, performance status, B symptoms, stage, number of nodal and extranodal sites involved, LDH, hemoglobin, longest diameter of the largest lymph node, presence of effusion and compression syndrome, circulating lymphoma cells, platelet count, serum albumin, bone marrow involvement, and s2m. For validation, we combined 175 patients with high tumo...
Introduction: We previously reported the results of the PRECIS trial with a median follow-up of 3... more Introduction: We previously reported the results of the PRECIS trial with a median follow-up of 33 months. Both whole brain radiotherapy (WBRT) and autologous stem cell transplantation (ACST) were effective according to the predetermined threshold. However, more relapses occurred in the WBRT arm. The 2-year event-free survival (EFS) from consolidation (relapse or death defined as event) were 69% (95% CI, 57% to 83%) and 87% (95% CI, 77% to 98%) after WBRT and ASCT, respectively (p = 0.03). Overall survival (OS) was similar in both arms. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. A longer follow-up is required to better assess the impact of the treatment on relapse, survival and late complications. We report here the results of the PRECIS trial with a median follow-up of 98.3 months [min= 4,1 - max= 131.1], focusing on the per protocol population from time of consolidation. Methods: Immunocompetent patients (18 to ...
Diffuse large B‐cell lymphoma (DLBCL) is an aggressive type of non‐Hodgkin lymphoma. The prevalen... more Diffuse large B‐cell lymphoma (DLBCL) is an aggressive type of non‐Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event‐free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high‐risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, β2‐microglobulin, hemoglobin, and albumin levels. The diagnosis‐to‐treatment interval was significantly shorter for hypercalcemic patients (P ...
Background Long-term outcome of chronic lymphocytic leukemia (CLL) patients (pts) under ibrutinib... more Background Long-term outcome of chronic lymphocytic leukemia (CLL) patients (pts) under ibrutinib therapy has been evaluated within clinical trials, and CLL progression seems to be strongly linked with the onset of BTK and PLCg2 mutations. These mutations have largely been studied in resistant pts. Limited data are available regarding the BTK and/or PLCγ2 mutations in pts on ibrutinib without evidence of disease progression. Ibrutinib was available in France during 2014 as an early access program (EAP) thus allowing the evaluation of prolonged use of Ibrutinib in a real-life setting. The objective of this study was to analyze the genetic profile of pts still on Ibrutinib after at least 3 years of treatment. We also explored minimal residual disease (MRD) and T-lymphocyte subsets. Results Data were collected from all pts who received ibrutinib via the EAP in 29 centers of the FILO group. Between February 2014 and April 2015, 204 pts began ibrutinib treatment. Only 63 (31%) remained o...
Introduction: The 17p deletion (del(17p)) resulting in loss of the TP53 gene is associated with i... more Introduction: The 17p deletion (del(17p)) resulting in loss of the TP53 gene is associated with impaired response to genotoxic agents and has an impact on PFS following BTK inhibitor and possibly also venetoclax. The del(17p) usually coincides with TP53 mutation, leading to the impairment of the p53-associated pathway. Sole TP53 mutations appear also associated with poor outcome in prospective trials. The iwCLL guidelines recommend to look for del(17p) and TP53 mutation before each line of treatment. An original approach is the functional assay, which highlights the functional abnormalities of p53 whether it is a TP53 gene disruption (del(17p) and/or TP53 mutation) or a defect of another actor in the p53 pathway. We aim to validate this functional assay on a prospective trial and to study the impact of p53 status on the clinical response regardless of the biological method. Methods: Clinical and biological data were collected from 74 CLL patients (pts) enrolled in the BOMP phase II ...
Background: Nivolumab demonstrated remarkable activity in patients with relapse or refractory (R/... more Background: Nivolumab demonstrated remarkable activity in patients with relapse or refractory (R/R) Hodgkin lymphoma (HL). However, long term efficacy and the need for a consolidation with allogenic stem cell transplantation remain unclear. Patient and method: We retrospectively analyzed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcome according to subsequent alloHSCT. Results: After a median follow-up of 31.5 months, the best overall response rate was 64%, including 37.3% complete response (CR). The median progression-free survival (PFS) was 12.1 months and median overall survival (OS) was not reached. At 3 years, PFS and OS rates were 35% and 65%, respectively. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a PR (median = not reached vs 10.1 months). In our cohort, 17 patients underwent consolidation with allogenic stem cells transplantation (alloHSCT) after nivolumab therapy (Fig...
The purpose of this study was to determine whether texture analysis features present on pretreatm... more The purpose of this study was to determine whether texture analysis features present on pretreatment unenhanced computed tomography (CT) images, derived from 18F-fluorodeoxyglucose positron emission/computed tomography (18-FDG PET/CT), can predict progression-free survival (PFS), progression-free survival at 24 months (PFS 24), time to next treatment (TTNT), and overall survival in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance. Seventy-two patients with follicular lymphoma were retrospectively included. Texture analysis was performed on unenhanced CT images extracted from 18-FDG PET/CT examinations that were obtained within one month before treatment. Skewness at a fine texture scale (SSF = 2) was an independent predictor of PFS (hazard ratio = 3.72 (95% CI: 1.15, 12.11), p = 0.028), PFS 24 (hazard ratio = 13.38; 95% CI: 1.29, 138.13; p = 0.029), and TTNT (hazard ratio = 5.11; 95% CI: 1.18, 22.13; p = 0.029). Skewness v...
Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diag... more Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diagnosis. Time to lymphoma treatment (TLT) initiation can however be very heterogeneous and risk factors of progression are poorly studied. Our study evaluated 201 pts with grade 1–3a low-tumor burden FL diagnosed in four French centers between 2010 and 2020 and managed by a watch and wait strategy in real-life settings. After a median follow-up of 4.8 years, the median TLT was 4.2 years (95% confidence interval, 3.1-5.5). On multivariate analysis, elevated lactate dehydrogenase (hazard ratio [HR] = 2.2; P = 0.02), more than 4 nodal areas involved (HR = 1.7; P = 0.02) and more than 1 extranodal involvement (HR = 2.7; P = 0.01) were identified as independent predictors of TLT. The median TLT was 5.8 years for pts with no risk factor, 2.4 years for 1 risk factor, and 1.3 years for >1 risk factors (P < 0.01). In a subanalysis of 75 pts staged with positron emission tomography-computed to...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global pandemic. Phase III trials have demonstrated excellent efficacies of mRNA vaccines against SARS-CoV-2 in large population studies (Baden LR, NEJM, 2021; Polack FP, NEJM, 2020). Immunosuppressed individuals such as chronic lymphocytic leukemia (CLL) patients are at risk for a suboptimal response to 2 vaccine doses (Herishanu Y, Blood, 2021). The French National Authority for Health recommends the use of a third dose in immunosuppressed patients. However, seroconversion rate after the triple-dose vaccine is not yet known. The objective of our study was to evaluate SARS-CoV-2 antibody responses after the first, second and third doses of the BNT162b2 and mRNA-1273 vaccines. Data were collected from 17 French Innovative Leukemia Organization (FILO) investigating centers and the French CLL patients' association (SILLC). SARS-CoV-2 IgG anti-Spike levels were measured at 4-6 weeks after eac...
Introduction. In follicular lymphoma (FL), no prognostic index has been built based on a cohort o... more Introduction. In follicular lymphoma (FL), no prognostic index has been built based on a cohort of patients treated only with initial immunochemotherapy. Given the emergence of new biomolecular and metabolic prognostic factors in FL, an easy-to-compute and reliable scoring system utilizing such variables could aid in trial stratification and routine clinical evaluation. Methods. The primary endpoint for model building was progression-free survival (PFS). For discovery, we used the large prospective PRIMA trial cohort of 1,135 patients treated with initial R-chemotherapy +/- R-maintenance. Variables considered for model building included age, sex, performance status, B symptoms, stage, number of nodal and extranodal sites involved, LDH, hemoglobin, longest diameter of the largest lymph node, presence of effusion and compression syndrome, circulating lymphoma cells, platelet count, serum albumin, bone marrow involvement, and s2m. For validation, we combined 175 patients with high tumo...
Introduction Adults with ITP usually respond to corticosteroids but typically relapse after disco... more Introduction Adults with ITP usually respond to corticosteroids but typically relapse after discontinuation. Rituximab is thought to be an effective off-label second-line treatment but only few prospective data exist about its long-term efficacy and its long-term safety is a matter of concern. The tolerance and particularly the risk of severe infection is a crucial factor for assessing the risk/benefit ratio of this treatment in ITP. Three years ago, we opened a non-interventional prospective registry in France to investigate the safety (primary outcome) and the efficacy of rituximab in off-trials adults with ITP (ClinicalTrials.Gov: NC1101295). Two hundred and fifty two patients were included on a two-year period. A follow-up duration of five-year is planned. We report here the first results after one year of follow-up. Methods The ITP-Ritux registry was set up by the French reference center of adult’s immune cytopenias. Thirty one centers participated to the study. Consecutive pat...
Introduction: We previously reported the results of the PRECIS trial with a median follow-up of 3... more Introduction: We previously reported the results of the PRECIS trial with a median follow-up of 33 months. Both whole brain radiotherapy (WBRT) and autologous stem cell transplantation (ACST) were effective according to the predetermined threshold. However, more relapses occurred in the WBRT arm. The 2-year event-free survival (EFS) from consolidation (relapse or death defined as event) were 69% (95% CI, 57% to 83%) and 87% (95% CI, 77% to 98%) after WBRT and ASCT, respectively (p = 0.03). Overall survival (OS) was similar in both arms. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. A longer follow-up is required to better assess the impact of the treatment on relapse, survival and late complications. We report here the results of the PRECIS trial with a median follow-up of 98.3 months [min= 4,1 - max= 131.1], focusing on the per protocol population from time of consolidation. Methods: Immunocompetent patients (18 to ...
Diffuse large B‐cell lymphoma (DLBCL) is an aggressive type of non‐Hodgkin lymphoma. The prevalen... more Diffuse large B‐cell lymphoma (DLBCL) is an aggressive type of non‐Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event‐free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high‐risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, β2‐microglobulin, hemoglobin, and albumin levels. The diagnosis‐to‐treatment interval was significantly shorter for hypercalcemic patients (P ...
Background Long-term outcome of chronic lymphocytic leukemia (CLL) patients (pts) under ibrutinib... more Background Long-term outcome of chronic lymphocytic leukemia (CLL) patients (pts) under ibrutinib therapy has been evaluated within clinical trials, and CLL progression seems to be strongly linked with the onset of BTK and PLCg2 mutations. These mutations have largely been studied in resistant pts. Limited data are available regarding the BTK and/or PLCγ2 mutations in pts on ibrutinib without evidence of disease progression. Ibrutinib was available in France during 2014 as an early access program (EAP) thus allowing the evaluation of prolonged use of Ibrutinib in a real-life setting. The objective of this study was to analyze the genetic profile of pts still on Ibrutinib after at least 3 years of treatment. We also explored minimal residual disease (MRD) and T-lymphocyte subsets. Results Data were collected from all pts who received ibrutinib via the EAP in 29 centers of the FILO group. Between February 2014 and April 2015, 204 pts began ibrutinib treatment. Only 63 (31%) remained o...
Introduction: The 17p deletion (del(17p)) resulting in loss of the TP53 gene is associated with i... more Introduction: The 17p deletion (del(17p)) resulting in loss of the TP53 gene is associated with impaired response to genotoxic agents and has an impact on PFS following BTK inhibitor and possibly also venetoclax. The del(17p) usually coincides with TP53 mutation, leading to the impairment of the p53-associated pathway. Sole TP53 mutations appear also associated with poor outcome in prospective trials. The iwCLL guidelines recommend to look for del(17p) and TP53 mutation before each line of treatment. An original approach is the functional assay, which highlights the functional abnormalities of p53 whether it is a TP53 gene disruption (del(17p) and/or TP53 mutation) or a defect of another actor in the p53 pathway. We aim to validate this functional assay on a prospective trial and to study the impact of p53 status on the clinical response regardless of the biological method. Methods: Clinical and biological data were collected from 74 CLL patients (pts) enrolled in the BOMP phase II ...
The purpose of this study was to determine whether texture analysis features present on pretreatm... more The purpose of this study was to determine whether texture analysis features present on pretreatment unenhanced computed tomography (CT) images, derived from 18F-fluorodeoxyglucose positron emission/computed tomography (18-FDG PET/CT), can predict progression-free survival (PFS), progression-free survival at 24 months (PFS 24), time to next treatment (TTNT), and overall survival in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance. Seventy-two patients with follicular lymphoma were retrospectively included. Texture analysis was performed on unenhanced CT images extracted from 18-FDG PET/CT examinations that were obtained within one month before treatment. Skewness at a fine texture scale (SSF = 2) was an independent predictor of PFS (hazard ratio = 3.72 (95% CI: 1.15, 12.11), p = 0.028), PFS 24 (hazard ratio = 13.38; 95% CI: 1.29, 138.13; p = 0.029), and TTNT (hazard ratio = 5.11; 95% CI: 1.18, 22.13; p = 0.029). Skewness v...
Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diag... more Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diagnosis. Time to lymphoma treatment (TLT) initiation can however be very heterogeneous and risk factors of progression are poorly studied. Our study evaluated 201 pts with grade 1–3a low-tumor burden FL diagnosed in four French centers between 2010 and 2020 and managed by a watch and wait strategy in real-life settings. After a median follow-up of 4.8 years, the median TLT was 4.2 years (95% confidence interval, 3.1-5.5). On multivariate analysis, elevated lactate dehydrogenase (hazard ratio [HR] = 2.2; P = 0.02), more than 4 nodal areas involved (HR = 1.7; P = 0.02) and more than 1 extranodal involvement (HR = 2.7; P = 0.01) were identified as independent predictors of TLT. The median TLT was 5.8 years for pts with no risk factor, 2.4 years for 1 risk factor, and 1.3 years for >1 risk factors (P < 0.01). In a subanalysis of 75 pts staged with positron emission tomography-computed to...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global pandemic. Phase III trials have demonstrated excellent efficacies of mRNA vaccines against SARS-CoV-2 in large population studies (Baden LR, NEJM, 2021; Polack FP, NEJM, 2020). Immunosuppressed individuals such as chronic lymphocytic leukemia (CLL) patients are at risk for a suboptimal response to 2 vaccine doses (Herishanu Y, Blood, 2021). The French National Authority for Health recommends the use of a third dose in immunosuppressed patients. However, seroconversion rate after the triple-dose vaccine is not yet known. The objective of our study was to evaluate SARS-CoV-2 antibody responses after the first, second and third doses of the BNT162b2 and mRNA-1273 vaccines. Data were collected from 17 French Innovative Leukemia Organization (FILO) investigating centers and the French CLL patients' association (SILLC). SARS-CoV-2 IgG anti-Spike levels were measured at 4-6 weeks after eac...
Introduction. In follicular lymphoma (FL), no prognostic index has been built based on a cohort o... more Introduction. In follicular lymphoma (FL), no prognostic index has been built based on a cohort of patients treated only with initial immunochemotherapy. Given the emergence of new biomolecular and metabolic prognostic factors in FL, an easy-to-compute and reliable scoring system utilizing such variables could aid in trial stratification and routine clinical evaluation. Methods. The primary endpoint for model building was progression-free survival (PFS). For discovery, we used the large prospective PRIMA trial cohort of 1,135 patients treated with initial R-chemotherapy +/- R-maintenance. Variables considered for model building included age, sex, performance status, B symptoms, stage, number of nodal and extranodal sites involved, LDH, hemoglobin, longest diameter of the largest lymph node, presence of effusion and compression syndrome, circulating lymphoma cells, platelet count, serum albumin, bone marrow involvement, and s2m. For validation, we combined 175 patients with high tumo...
Introduction: We previously reported the results of the PRECIS trial with a median follow-up of 3... more Introduction: We previously reported the results of the PRECIS trial with a median follow-up of 33 months. Both whole brain radiotherapy (WBRT) and autologous stem cell transplantation (ACST) were effective according to the predetermined threshold. However, more relapses occurred in the WBRT arm. The 2-year event-free survival (EFS) from consolidation (relapse or death defined as event) were 69% (95% CI, 57% to 83%) and 87% (95% CI, 77% to 98%) after WBRT and ASCT, respectively (p = 0.03). Overall survival (OS) was similar in both arms. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. A longer follow-up is required to better assess the impact of the treatment on relapse, survival and late complications. We report here the results of the PRECIS trial with a median follow-up of 98.3 months [min= 4,1 - max= 131.1], focusing on the per protocol population from time of consolidation. Methods: Immunocompetent patients (18 to ...
Diffuse large B‐cell lymphoma (DLBCL) is an aggressive type of non‐Hodgkin lymphoma. The prevalen... more Diffuse large B‐cell lymphoma (DLBCL) is an aggressive type of non‐Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event‐free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high‐risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, β2‐microglobulin, hemoglobin, and albumin levels. The diagnosis‐to‐treatment interval was significantly shorter for hypercalcemic patients (P ...
Background Long-term outcome of chronic lymphocytic leukemia (CLL) patients (pts) under ibrutinib... more Background Long-term outcome of chronic lymphocytic leukemia (CLL) patients (pts) under ibrutinib therapy has been evaluated within clinical trials, and CLL progression seems to be strongly linked with the onset of BTK and PLCg2 mutations. These mutations have largely been studied in resistant pts. Limited data are available regarding the BTK and/or PLCγ2 mutations in pts on ibrutinib without evidence of disease progression. Ibrutinib was available in France during 2014 as an early access program (EAP) thus allowing the evaluation of prolonged use of Ibrutinib in a real-life setting. The objective of this study was to analyze the genetic profile of pts still on Ibrutinib after at least 3 years of treatment. We also explored minimal residual disease (MRD) and T-lymphocyte subsets. Results Data were collected from all pts who received ibrutinib via the EAP in 29 centers of the FILO group. Between February 2014 and April 2015, 204 pts began ibrutinib treatment. Only 63 (31%) remained o...
Introduction: The 17p deletion (del(17p)) resulting in loss of the TP53 gene is associated with i... more Introduction: The 17p deletion (del(17p)) resulting in loss of the TP53 gene is associated with impaired response to genotoxic agents and has an impact on PFS following BTK inhibitor and possibly also venetoclax. The del(17p) usually coincides with TP53 mutation, leading to the impairment of the p53-associated pathway. Sole TP53 mutations appear also associated with poor outcome in prospective trials. The iwCLL guidelines recommend to look for del(17p) and TP53 mutation before each line of treatment. An original approach is the functional assay, which highlights the functional abnormalities of p53 whether it is a TP53 gene disruption (del(17p) and/or TP53 mutation) or a defect of another actor in the p53 pathway. We aim to validate this functional assay on a prospective trial and to study the impact of p53 status on the clinical response regardless of the biological method. Methods: Clinical and biological data were collected from 74 CLL patients (pts) enrolled in the BOMP phase II ...
Background: Nivolumab demonstrated remarkable activity in patients with relapse or refractory (R/... more Background: Nivolumab demonstrated remarkable activity in patients with relapse or refractory (R/R) Hodgkin lymphoma (HL). However, long term efficacy and the need for a consolidation with allogenic stem cell transplantation remain unclear. Patient and method: We retrospectively analyzed 78 patients with R/R HL treated with nivolumab in the French Early Access Program and compared their outcome according to subsequent alloHSCT. Results: After a median follow-up of 31.5 months, the best overall response rate was 64%, including 37.3% complete response (CR). The median progression-free survival (PFS) was 12.1 months and median overall survival (OS) was not reached. At 3 years, PFS and OS rates were 35% and 65%, respectively. Patients reaching a CR upon nivolumab had a significantly longer PFS than those reaching a PR (median = not reached vs 10.1 months). In our cohort, 17 patients underwent consolidation with allogenic stem cells transplantation (alloHSCT) after nivolumab therapy (Fig...
The purpose of this study was to determine whether texture analysis features present on pretreatm... more The purpose of this study was to determine whether texture analysis features present on pretreatment unenhanced computed tomography (CT) images, derived from 18F-fluorodeoxyglucose positron emission/computed tomography (18-FDG PET/CT), can predict progression-free survival (PFS), progression-free survival at 24 months (PFS 24), time to next treatment (TTNT), and overall survival in patients with high-tumor-burden follicular lymphoma treated with immunochemotherapy and rituximab maintenance. Seventy-two patients with follicular lymphoma were retrospectively included. Texture analysis was performed on unenhanced CT images extracted from 18-FDG PET/CT examinations that were obtained within one month before treatment. Skewness at a fine texture scale (SSF = 2) was an independent predictor of PFS (hazard ratio = 3.72 (95% CI: 1.15, 12.11), p = 0.028), PFS 24 (hazard ratio = 13.38; 95% CI: 1.29, 138.13; p = 0.029), and TTNT (hazard ratio = 5.11; 95% CI: 1.18, 22.13; p = 0.029). Skewness v...
Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diag... more Patients (pts) with asymptomatic low-burden follicular lymphoma (FL) are usually observed at diagnosis. Time to lymphoma treatment (TLT) initiation can however be very heterogeneous and risk factors of progression are poorly studied. Our study evaluated 201 pts with grade 1–3a low-tumor burden FL diagnosed in four French centers between 2010 and 2020 and managed by a watch and wait strategy in real-life settings. After a median follow-up of 4.8 years, the median TLT was 4.2 years (95% confidence interval, 3.1-5.5). On multivariate analysis, elevated lactate dehydrogenase (hazard ratio [HR] = 2.2; P = 0.02), more than 4 nodal areas involved (HR = 1.7; P = 0.02) and more than 1 extranodal involvement (HR = 2.7; P = 0.01) were identified as independent predictors of TLT. The median TLT was 5.8 years for pts with no risk factor, 2.4 years for 1 risk factor, and 1.3 years for >1 risk factors (P < 0.01). In a subanalysis of 75 pts staged with positron emission tomography-computed to...
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global... more Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for an ongoing global pandemic. Phase III trials have demonstrated excellent efficacies of mRNA vaccines against SARS-CoV-2 in large population studies (Baden LR, NEJM, 2021; Polack FP, NEJM, 2020). Immunosuppressed individuals such as chronic lymphocytic leukemia (CLL) patients are at risk for a suboptimal response to 2 vaccine doses (Herishanu Y, Blood, 2021). The French National Authority for Health recommends the use of a third dose in immunosuppressed patients. However, seroconversion rate after the triple-dose vaccine is not yet known. The objective of our study was to evaluate SARS-CoV-2 antibody responses after the first, second and third doses of the BNT162b2 and mRNA-1273 vaccines. Data were collected from 17 French Innovative Leukemia Organization (FILO) investigating centers and the French CLL patients' association (SILLC). SARS-CoV-2 IgG anti-Spike levels were measured at 4-6 weeks after eac...
Introduction. In follicular lymphoma (FL), no prognostic index has been built based on a cohort o... more Introduction. In follicular lymphoma (FL), no prognostic index has been built based on a cohort of patients treated only with initial immunochemotherapy. Given the emergence of new biomolecular and metabolic prognostic factors in FL, an easy-to-compute and reliable scoring system utilizing such variables could aid in trial stratification and routine clinical evaluation. Methods. The primary endpoint for model building was progression-free survival (PFS). For discovery, we used the large prospective PRIMA trial cohort of 1,135 patients treated with initial R-chemotherapy +/- R-maintenance. Variables considered for model building included age, sex, performance status, B symptoms, stage, number of nodal and extranodal sites involved, LDH, hemoglobin, longest diameter of the largest lymph node, presence of effusion and compression syndrome, circulating lymphoma cells, platelet count, serum albumin, bone marrow involvement, and s2m. For validation, we combined 175 patients with high tumo...
Introduction Adults with ITP usually respond to corticosteroids but typically relapse after disco... more Introduction Adults with ITP usually respond to corticosteroids but typically relapse after discontinuation. Rituximab is thought to be an effective off-label second-line treatment but only few prospective data exist about its long-term efficacy and its long-term safety is a matter of concern. The tolerance and particularly the risk of severe infection is a crucial factor for assessing the risk/benefit ratio of this treatment in ITP. Three years ago, we opened a non-interventional prospective registry in France to investigate the safety (primary outcome) and the efficacy of rituximab in off-trials adults with ITP (ClinicalTrials.Gov: NC1101295). Two hundred and fifty two patients were included on a two-year period. A follow-up duration of five-year is planned. We report here the first results after one year of follow-up. Methods The ITP-Ritux registry was set up by the French reference center of adult’s immune cytopenias. Thirty one centers participated to the study. Consecutive pat...
Introduction: We previously reported the results of the PRECIS trial with a median follow-up of 3... more Introduction: We previously reported the results of the PRECIS trial with a median follow-up of 33 months. Both whole brain radiotherapy (WBRT) and autologous stem cell transplantation (ACST) were effective according to the predetermined threshold. However, more relapses occurred in the WBRT arm. The 2-year event-free survival (EFS) from consolidation (relapse or death defined as event) were 69% (95% CI, 57% to 83%) and 87% (95% CI, 77% to 98%) after WBRT and ASCT, respectively (p = 0.03). Overall survival (OS) was similar in both arms. Cognitive impairment was observed after WBRT, whereas cognitive functions were preserved or improved after ASCT. A longer follow-up is required to better assess the impact of the treatment on relapse, survival and late complications. We report here the results of the PRECIS trial with a median follow-up of 98.3 months [min= 4,1 - max= 131.1], focusing on the per protocol population from time of consolidation. Methods: Immunocompetent patients (18 to ...
Diffuse large B‐cell lymphoma (DLBCL) is an aggressive type of non‐Hodgkin lymphoma. The prevalen... more Diffuse large B‐cell lymphoma (DLBCL) is an aggressive type of non‐Hodgkin lymphoma. The prevalence of hypercalcemia in this neoplasm and its prognostic significance is unclear. We retrospectively evaluated the prevalence of hypercalcemia at diagnosis of DLBCL and explored associations of hypercalcemia with clinical factors and outcome. Outcome was assessed using event‐free survival at 24 months (EFS24). A total of 305 patients (248 de novo DLBCL and 57 transformed indolent lymphomas) diagnosed between 2006 and 2018 in Reims were analyzed. The prevalence of calcemia >10.5 mg/dL at diagnosis of de novo DLBCL and transformed indolent lymphomas was 23% and 26%, respectively. Hypercalcemia in de novo DLBCL was strongly associated with high‐risk features, especially with International Prognostic Index (IPI) components, but also with B symptoms, β2‐microglobulin, hemoglobin, and albumin levels. The diagnosis‐to‐treatment interval was significantly shorter for hypercalcemic patients (P ...
Background Long-term outcome of chronic lymphocytic leukemia (CLL) patients (pts) under ibrutinib... more Background Long-term outcome of chronic lymphocytic leukemia (CLL) patients (pts) under ibrutinib therapy has been evaluated within clinical trials, and CLL progression seems to be strongly linked with the onset of BTK and PLCg2 mutations. These mutations have largely been studied in resistant pts. Limited data are available regarding the BTK and/or PLCγ2 mutations in pts on ibrutinib without evidence of disease progression. Ibrutinib was available in France during 2014 as an early access program (EAP) thus allowing the evaluation of prolonged use of Ibrutinib in a real-life setting. The objective of this study was to analyze the genetic profile of pts still on Ibrutinib after at least 3 years of treatment. We also explored minimal residual disease (MRD) and T-lymphocyte subsets. Results Data were collected from all pts who received ibrutinib via the EAP in 29 centers of the FILO group. Between February 2014 and April 2015, 204 pts began ibrutinib treatment. Only 63 (31%) remained o...
Introduction: The 17p deletion (del(17p)) resulting in loss of the TP53 gene is associated with i... more Introduction: The 17p deletion (del(17p)) resulting in loss of the TP53 gene is associated with impaired response to genotoxic agents and has an impact on PFS following BTK inhibitor and possibly also venetoclax. The del(17p) usually coincides with TP53 mutation, leading to the impairment of the p53-associated pathway. Sole TP53 mutations appear also associated with poor outcome in prospective trials. The iwCLL guidelines recommend to look for del(17p) and TP53 mutation before each line of treatment. An original approach is the functional assay, which highlights the functional abnormalities of p53 whether it is a TP53 gene disruption (del(17p) and/or TP53 mutation) or a defect of another actor in the p53 pathway. We aim to validate this functional assay on a prospective trial and to study the impact of p53 status on the clinical response regardless of the biological method. Methods: Clinical and biological data were collected from 74 CLL patients (pts) enrolled in the BOMP phase II ...
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Papers by Alain Delmer