The pharmacology of blinatumomab: state of the art on pharmacodynamics, pharmacokinetics, adverse drug reactions and evaluation in clinical trials.

WHAT IS KNOWN AND OBJECTIVE: Bispecific drugs (BDs) belong to the family of immunotherapies along with checkpoint inhibitors and CAR-T cells. In the field of oncology, BDs are designed to simultaneously bind a tumour antigen on the one side and an antigen present on the surface of effector cells on the other. This review summarizes the information available to date on the first marketed BiTE-format bispecific antibody, blinatumomab BLINCYTO® in acute lymphoblastic leukaemia. METHODS: A literature search was conducted in the PubMed database by including studies published in English using the term blinatumomab. Furthermore, bibliographies of selected references were also evaluated for relevant articles. Clinical trial (CT) data were retrieved from clinicaltrials.gov (ongoing trials, adverse events [AEs]) and global pharmacovigilance data were retrieved from VigiBase®. RESULTS AND DISCUSSION: Blinatumomab is a fusion protein which consists of two single-chain variable fragments arranged in tandem: the first binds the CD19 surface antigen of all B cells and the second targets the CD3 antigen of T cells. Binding of blinatumomab to B and T cells induces apoptosis of B cells after secretion of granzymes and perforins by T cells. T-cell activation results in secretion of pro-inflammatory cytokines and upregulation of activation markers and adhesion molecules on the surface of T cells. The major CTs that led to an indication show increased overall survival with blinatumomab with better efficacy in patients in haematological remission with minimal residual disease ≥10-3 . The major AEs are cytokine release syndrome, neurotoxicity and hypogammaglobulinemia. The three most frequent system organ classes in CTs are haematological, gastrointestinal and general disorders. These results are also found in VigiBase® but neurological disorders and infections appear more frequently in real life. WHAT IS NEW AND CONCLUSION: This review summarizes the current knowledge of blinatumomab in the literature. The subject of many CTs is to improve the route of administration and expand the indications for treatment.

Late relapse after hematopoietic stem cell transplantation for acute leukemia: a retrospective study by SFGM-TC.

Late relapse (LR) after allogeneic hematopoietic stem cell transplantation (AHSCT) for acute leukemia is a rare event (nearly 4.5%) and raises the questions of prognosis and outcome after salvage therapy. We performed a retrospective multicentric study between January 1, 2010, and December 31, 2016, using data from the French national retrospective register ProMISe provided by the SFGM-TC (French Society for Bone Marrow Transplantation and Cellular Therapy). We included patients presenting with LR, defined as a relapse occurring at least 2 years after AHSCT. We used the Cox model to identify prognosis factors associated with LR. During the study period, a total of 7582 AHSCTs were performed in 29 centers, and 33.8% of patients relapsed. Among them, 319 (12.4%) were considered to have LR, representing an incidence of 4.2% for the entire cohort. The full dataset was available for 290 patients, including 250 (86.2%) with acute myeloid leukemia and 40 (13.8%) with acute lymphoid leukemia. The median interval from AHSCT to LR was 38.2 months (interquartile range [IQR], 29.2 to 49.7 months), and 27.2% of the patients had extramedullary involvement at LR (17.2% exclusively and 10% associated with medullary involvement). One-third of the patients had persistent full donor chimerism at LR. Median overall survival (OS) after LR was 19.9 months (IQR, 5.6 to 46.4 months). The most common salvage therapy was induction regimen (55.5%), with complete remission (CR) obtained in 50.7% of cases. Ninety-four patients (38.5%) underwent a second AHSCT, with a median OS of 20.4 months (IQR, 7.1 to 49.1 months). Nonrelapse mortality after second AHSCT was 18.2%. The Cox model identified the following factors as associated with delay of LR: disease status not in first CR at first HSCT (odds ratio [OR], 1.31; 95% confidence interval [CI], 1.04 to 1.64; P = .02) and the use of post-transplantation cyclophosphamide (OR, 2.23; 95% CI, 1.21 to 4.14; P = .01). Chronic GVHD appeared to be a protective factor (OR, .64; 95% CI, .42 to .96; P = .04). The prognosis of LR is better than in early relapse, with a median OS after LR of 19.9 months. Salvage therapy associated with a second AHSCT improves outcome and is feasible, without creating excess toxicity.

Caval replacement with parietal peritoneum tube graft for septic thrombophlebitis after hepatectomy: A case report.

BACKGROUND: Caval vein thrombosis after hepatectomy is rare, although it increases mortality and morbidity. The evolution of this thrombosis into a septic thrombophlebitis responsible for persistent septicaemia after a hepatectomy has not been reported to date in the literature. We here report the management of a 54-year-old woman operated for a peripheral cholangiocarcinoma who developed a suppurated thrombophlebitis of the vena cava following a hepatectomy. CASE SUMMARY: This patient was operated by left lobectomy extended to segment V with bile duct resection and Roux-en-Y hepaticojejunostomy. After the surgery, she developed Streptococcus anginosus, Escherichia coli, and Enterococcus faecium bacteraemias, as well as Candida albicans fungemia. A computed tomography scan revealed a bilioma which was percutaneously drained. Despite adequate antibiotic therapy, the patient's condition remained septic. A diagnosis of septic thrombophlebitis of the vena cava was made on post-operative day 25. The patient was then operated again for a surgical thrombectomy and complete caval reconstruction with a parietal peritoneum tube graft. Use of the peritoneum as a vascular graft is an inexpensive technique, it is readily and rapidly available, and it allows caval replacement in a septic area. Septic thrombophlebitis of the vena cava after hepatectomy has not been described previously and it warrants being added to the spectrum of potential complications of this procedure. CONCLUSION: Septic thrombophlebitis of the vena cava was successfully treated with antibiotic and anticoagulation treatments, prompt surgical thrombectomy and caval reconstruction.