French Retrospective Database Analysis of Patient Characteristics and Treatment Patterns in Patients with R/R FLT3-Mutated AML: A Registry-Based Cohort Study.

INTRODUCTION: There is a dearth of evidence to document treatment of FMS-like tyrosine kinase 3 (FLT3)-mutated acute myeloid leukemia (AML) in real-world settings before the introduction of FLT3 inhibitors. A retrospective cohort study was conducted to understand treatment practices prior to the availability of FLT3 inhibitors in patients with FLT3-mutated AML from two registries in France. METHODS: Patient data from January 1, 2009 to December 31, 2017 were collected from the Hauts-de-France and Midi-Pyrénées registries. Patients aged ≥ 18 years at diagnosis with FLT3-mutated AML were included. Demographic and disease characteristics of patients with FLT3-mutated AML and relapsed or refractory (R/R) FLT3-mutated AML were documented. Treatment regimens, overall survival (OS), and event-free survival were assessed in patients with R/R FLT3-mutated AML who did not participate in clinical trials. RESULTS: Overall, 819 and 1244 adult patients with AML from the Midi-Pyrénées and Hauts-de-France cohorts, respectively, underwent FLT3 mutation testing; 172 (21.0%) and 263 (21.1%) patients, respectively, had a FLT3 mutation. Primary R/R status was identified in 41.3% (n = 71/172) of the Midi-Pyrénées and 34.6% (n = 91/263) of the Hauts-de-France cohorts. Before R/R AML diagnosis, 82.0% and 97.5% of patients in the Midi-Pyrénées and Hauts-de-France cohorts, respectively, achieved complete remission (CR) or CR with incomplete hematologic recovery (CRi) following induction chemotherapy; after diagnosis of R/R AML, CR/CRi rates with salvage therapy were 33.3% and 28.1%, respectively. Median OS (interquartile range) in patients receiving salvage therapy (n = 49, n = 78) was 5.2 (2.3-11.1) and 6.1 (2.5-35.2) months, in the Midi-Pyrénées and Hauts-de-France cohorts, respectively. Across both cohorts, patients with R/R FLT3-mutated AML had low rates of CR/CRi with salvage therapy and a median OS of approximately 6 months. CONCLUSION: Before FLT3 inhibitor availability, real-world treatment patterns and outcomes in French patients with R/R FLT3-mutated AML were consistent with clinical trial data, highlighting a poor prognosis and unmet need for effective treatment.

Acute myeloid leukemia is a cancer affecting the blood and bone marrow. The presence of specific mutations in the FMS-like tyrosine kinase 3 (FLT3) gene in patients with acute myeloid leukemia can negatively impact response to standard chemotherapy. Patients with these mutations may not respond to chemotherapy or have a shortened duration of response causing a return of the disease, which in turn substantially decreases their life span. In the era prior to the availability of drugs specifically designed to counteract the negative effects of FLT3 mutations, evidence related to patient characteristics and treatment effects in individuals with acute myeloid leukemia harboring FLT3 mutations was mainly derived from clinical studies, with little evidence based on real-world experience. To better understand real-world patient characteristics and treatment effects in patients with acute myeloid leukemia and FLT3 mutations, we analyzed patients from two French registries, Midi-Pyrénées and Hauts-de-France, with a focus on patients who did not respond to or whose disease returned after initial chemotherapy. Patient data from between January 2009 and December 2017 included patients with FLT3-mutated acute myeloid leukemia from Midi-Pyrénées and Hauts-de-France who did not respond to or had recurrent disease after responding to initial chemotherapy, had low response to salvage chemotherapy, and a survival duration of 6 months or less. Our real-world observations in patients with relapsed or refractory FLT3-mutated acute myeloid leukemia from these two registries were consistent with results reported in clinical trials. Our results highlight the bleak forecast for these patients in the absence of effective drugs.

Quality of life in adults with acute lymphoblastic leukemia in France: results from a French cross-sectional study.

In recent years, treatment of acute lymphoblastic leukemia (ALL) has improved substantially, leading to longer survival. This has necessitated a greater focus on health-related quality of life (HRQoL), but data are lacking. In a part-prospective, part-retrospective study, we enrolled 219 adults with ALL in France to assess the impact of key disease and treatment characteristics on HRQoL. Overall HRQoL and most specific QoL domain scores were consistently better among patients receiving front-line therapy, those currently in complete remission, and those who had previously received hematopoietic stem-cell transplantation. Furthermore, HRQoL was consistently impaired in patients with minimal residual disease present (MRD+). In multivariate analyses, multiple lines of therapy, MRD+, leukopenia, comorbidities, and anemia were significantly associated with impaired HRQoL. This study provides real-world data on HRQoL in adults with ALL in France and shows the positive impact of MRD-negative status on HRQoL.

Monotherapy with pixantrone in histologically confirmed relapsed or refractory aggressive B-cell non-Hodgkin lymphoma: post-hoc analyses from a phase III trial.

This post hoc analysis of a phase 3 trial explored the effect of pixantrone in patients (50 pixantrone, 47 comparator) with relapsed or refractory aggressive B-cell non-Hodgkin lymphoma (NHL) confirmed by centralized histological review. Patients received 28-d cycles of 85 mg/m(2) pixantrone dimaleate (equivalent to 50 mg/m(2) in the approved formulation) on days 1, 8 and 15, or comparator. The population was subdivided according to previous rituximab use and whether they received the study treatment as 3rd or 4th line. Median number of cycles was 4 (range, 2-6) with pixantrone and 3 (2-6) with comparator. In 3rd or 4th line, pixantrone was associated with higher complete response (CR) (23·1% vs. 5·1% comparator, P = 0·047) and overall response rate (ORR, 43·6% vs. 12·8%, P = 0·005). In 3rd or 4th line with previous rituximab (20 pixantrone, 18 comparator), pixantrone produced better ORR (45·0% vs. 11·1%, P = 0·033), CR (30·0% vs. 5·6%, P = 0·093) and progression-free survival (median 5·4 vs. 2·8 months, hazard ratio 0·52, 95% confidence interval 0·26-1·04) than the comparator. Similar results were found in patients without previous rituximab. There were no unexpected safety issues. Pixantrone monotherapy is more effective than comparator in relapsed or refractory aggressive B-cell NHL in the 3rd or 4th line setting, independently of previous rituximab.

Characterization of leucocin B-KM432Bz from Leuconostoc pseudomesenteroides isolated from boza, and comparison of its efficiency to pediocin PA-1.

A bacteriocin-producing bacterium was isolated from boza and identified as Leuconostoc pseudomesenteroides KM432Bz. The antimicrobial peptide was purified and shown to be identical to other class IIa bacteriocins: leucocin A from Leuconostoc gelidum UAL-187 and Leuconostoc pseudomesenteroides QU15 and leucocin B from Leuconostoc carnosum Ta11a. The bacteriocin was named leucocin B-KM432Bz. Leucocin B-KM432Bz gene cluster encodes the bacteriocin precursor (lcnB), the immunity protein (lcnI) and the dedicated export machinery (lcnD and lcnE). A gene of unknown and non-essential function (lcnC), which is interrupted by an insertion sequence of the IS30 family, is localized between lcnB and lcnD. The activity of leucocin B-KM432Bz requires subunit C of the EII(t) Man mannose permease, which is the receptor for entry into target cells. The determination of the minimum inhibitory concentrations revealed the lowest values for leucocin B-KM432Bz over Listeria strains, with 4 to 32 fold better efficiency than pediocin PA-1.