Therapeutic management and outcome of patients with advanced systemic mastocytosis treated with midostaurin: A comprehensive real-life study in the French national healthcare database.

Advanced Systemic Mastocytosis (Adv-SM) is rare and has a poor prognosis. Midostaurin (Rydapt® ) is one of the few treatments for Adv-SM in Europe. The study aims were to describe the characteristics of patients treated with midostaurin, their treatment modalities, outcomes, and serious events requiring hospitalization. This retrospective observational study was conducted using the French National Healthcare Database (SNDS) and included adult Adv-SM patients treated with midostaurin between 01-01-2012 and 09-30-2018. Kaplan-Meier method was used to assess survival and treatment duration. Eighty-one patients were included: 37 with Aggressive Systemic Mastocytosis (SM) (46%), 31 with SM with an Associated Hematological Neoplasm (38%), and 4 with Mast Cell Leukemia (5%). The SM subtype was undetermined in 9 patients (11%). The median age was 67 years; 64% of patients were male. Over the mean follow-up of 11.4 months, median midostaurin treatment duration was 8.4 months and 28 patients (35%) were still under treatment at the end of the study. One-year and 5-year overall survival rates estimated since the time of diagnosis were 83% and 56%, respectively. Twelve serious events (among those frequently reported during clinical trials and compassionate use) requiring hospitalization were identified; a causal association with Adv-SM treatment could neither be excluded nor established. In this first real-life study on patients treated with midostaurin for Adv-SM, the patients' characteristics, their management, treatment discontinuation, and survival were in line with previous results (compassionate use and clinical trials).

Cost-effectiveness of midostaurin in the treatment of newly diagnosed FLT3-mutated acute myeloid leukemia in France.

BACKGROUND: Midostaurin (MIDO) combined with standard chemotherapy was approved by the European Medicines Agency in 2017 for the treatment of adults with newly diagnosed FLT3-mutated acute myeloid leukemia (AML) based on results from the RATIFY trial. METHODS: A cost-effectiveness model was developed to compare MIDO and standard-of-care (SOC) to SOC alone in France. Per Haute Autorité de Santé (HAS) guidelines, a partitioned survival model with eight health states was used: diagnosis/induction, complete remission, relapse, hematopoietic stem cell transplantation (HSCT), HSCT recovery, post-HSCT recovery (stabilized after HSCT recovery), post-HSCT relapse, and mortality. A lifetime horizon was used beginning at diagnosis with a "cure model,", which assumed natural mortality after trial cut-off. Utility values were obtained from a systematic literature review and included disutilities. Resource utilization was based on HAS clinical guidelines and a survey of French physicians and included drugs and administration, adverse events, routine medical care, HSCT, and end-of-life care costs. RESULTS: In RATIFY and after extrapolation, MIDO improved survival compared to SOC, translating into MIDO-treated patients gaining 1.12 life years (LYs) and 1.23 quality-adjusted life years (QALYs) versus SOC. The incremental cost-effectiveness ratio (ICER) for MIDO versus SOC was €68,781 per LY and €62,305 per QALY. Sensitivity analyses showed consistency with base case findings. CONCLUSIONS: MIDO represents a clinically significant advancement in the management of newly diagnosed FLT3-mutated AML. In this analysis, MIDO add-on therapy showed gains in LYs and QALYs versus SOC alone and was found to be a cost-effective option at a €100,000 per QALY threshold for end-of-life treatment.

Incidence of delayed graft function and wound healing complications after deceased-donor kidney transplantation is not affected by de novo everolimus.

BACKGROUND: Concerns about delayed graft function (DGF) and wound healing complications with sirolimus has led to suggestions that everolimus introduction could be delayed after transplantation. METHODS: In a prospective, multicenter, open-label study, deceased-donor kidney transplant recipients at protocol-specified risk of DGF (defined as > or =1 dialysis session during the first week posttransplant excluding day 1) were randomized to start everolimus therapy on day 1 posttransplant (immediate everolimus [IE]), or from week 5 (delayed everolimus [DE]) with mycophenolic acid until everolimus was initiated. All patients received anti-interleukin-2 receptor antibodies, cyclosporine A, and corticosteroids. A planned 3-month analysis from this 12-month study is presented here. RESULTS: One hundred and thirty-nine patients were randomized (IE 65, DE 74). The primary composite endpoint: biopsy-proven acute rejection, graft loss, death, DGF, wound healing events, or lost to follow-up at month 3, occurred in 36 IE patients (55.4%) and 47 DE patients (63.5%, P=0.387). The incidence of DGF was similar between groups (IE 24.6%, DE 24.3%; n.s.). Wound healing events of any type occurred in 40.0% and 41.9% of IE and DE patients (n.s.); events relating to initial transplant surgery occurred in 36.9% IE patients and 37.8% DE patients (n.s.), most of which were fluid collections. Study drug was discontinued due to adverse events or graft loss in 13 IE (20.0%) and 17 DE patients (23.0%). CONCLUSIONS: Findings from this randomized, multicenter trial indicate that kidney function recovery, wound healing, efficacy, and tolerance are similar at 3 months posttransplant with immediate or DE in patients at protocol-specified risk of DGF.

Lower risk of infectious deaths in cardiac transplant patients receiving basiliximab versus anti-thymocyte globulin as induction therapy.

BACKGROUND: Conventional antibody induction therapy is currently used in heart transplantation despite safety concerns. This 6-month, prospective, randomized, multicenter, open-label study examined whether basiliximab offers a tolerability benefit compared with anti-thymocyte globulin (ATG) while maintaining similar efficacy in de novo heart transplant recipients. METHODS: Adult heart transplant recipients were randomized to receive basiliximab (20 mg on Day 0 and Day 4) or ATG (2.5 mg/kg/day for 3 to 5 days) with cyclosporine, mycophenolate mofetil and steroids. The primary safety end-point was a composite of serum sickness, fever, cutaneous rash, anaphylaxis, infection, thrombocytopenia, leukopenia and post-transplant proliferative disease. Efficacy was assessed by a composite end-point of death, graft loss, acute rejection Grade > 1B, acute rejection associated with hemodynamic compromise or treated with antibody therapy, or loss to follow-up, whichever occurred first. RESULTS: Eighty patients were randomized and analyzed. By Month 6, the incidence of the composite safety end-point was significantly lower with basiliximab than with ATG (50.0% vs 78.6%, p = 0.01), and infectious death was less frequent in the basiliximab group (0 of 38 vs 6 of 42, p = 0.027). The composite efficacy end-point occurred in 24 patients (63.2%) in the basiliximab arm vs 28 patients (66.7%, p = not significant [NS]) receiving ATG. Acute rejection episodes of Grade > or = 1B were reported with similar frequency (50% with basiliximab vs 45.2% with ATG, p = NS); 7 patients (18.4%) in the basiliximab group and 3 (7.1%) in the ATG group had rejection Grade > or = 3A. CONCLUSIONS: These results suggest that basiliximab offers improved tolerability with similar efficacy compared with current polyclonal antibody induction therapy in de novo heart transplant patients.