Mast cell activation is common and possibly necessary for maintenance of survival. Disordered mast cell activation occurs when mast cells are pathologically overproduced or if their activation is out of proportion to the perceived threat to homeostasis. Mast cell activation syndrome refers to a group of disorders with diverse causes presenting with episodic multisystem symptoms as the result of mast cell mediator release. Despite introduction of diagnostic criteria and some advances in treatment in the last decade, many areas of mast cell activation syndrome are in need of research. This article reviews our current knowledge about the various types of mast cell activation disorders, their treatment, and areas of uncertainty in need of future investigation.

Mast cell activation syndromes.

52 Application of gee procedures for sample size calculations in repeated measures experiments

Objective: To assess masitinib in the treatment of ALS. Methods: Double-blind study, randomly assigning 394 patients (1:1:1) to receive riluzole (100 mg/d) plus placebo or masitinib at 4.5 or 3.0 m...

/pdf/masitinib-as-an-add-on-therapy-to-riluzole-in-patients-with-7x2fhv5o78.pdf

Masitinib as an add-on therapy to riluzole in patients with amyotrophic lateral sclerosis: a randomized clinical trial

Mast Cells as Drivers of Disease and Therapeutic Targets

Patients with advanced systemic mastocytosis (SM) (e.g. aggressive SM (ASM), SM with an associated hematologic neoplasm (SM-AHN) and mast cell leukemia (MCL)) have limited treatment options and exhibit reduced survival. Midostaurin is an oral multikinase inhibitor that inhibits D816V-mutated KIT, a primary driver of SM pathogenesis. We conducted a phase II trial of midostaurin 100 mg twice daily, administered as 28-day cycles, in 26 patients (ASM, n=3; SM-AHN, n= 17; MCL, n=6) with at least one sign of organ damage. During the first 12 cycles, the overall response rate was 69% (major/partial response: 50/19%) with clinical benefit in all advanced SM variants. With ongoing therapy, 2 patients achieved a complete remission of their SM. Midostaurin produced a ⩾50% reduction in bone marrow mast cell burden and serum tryptase level in 68% and 46% of patients, respectively. Median overall survival for the entire cohort was 40 months, and 18.5 months for MCL patients. Low-grade gastrointestinal side effects were common and manageable with antiemetics. The most frequent grade 3/4 nonhematologic and hematologic toxicities were asymptomatic hyperlipasemia (15%) and anemia (12%). With median follow-up of 10 years, no unexpected toxicities emerged. These data establish the durable activity and tolerability of midostaurin in advanced SM.

Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis: 10-year median follow-up of a phase II trial

https://hal.archives-ouvertes.fr/hal-01787376/document

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study


 
 
 Outcomes of kidney transplantation for patients with renal AA amyloidosis are uncertain, with reports of poor survival and high allograft recurrence. However, recent advances in biotherapies, especially anti-IL-1 treatments, may have improved patients’ outcome in the transplantation setting.
 
 
 
 We conducted a retrospective multicenter matched cohort study in 26 French centers reporting all patients with AA amyloidosis who received a kidney transplant between 2008 and 2018, and compared them to matched control patients (ratio 1:2 controls) who received a kidney transplant for other causes
 
 
 
 Eighty-six AA amyloidosis transplants and 157 control transplants were included. Median age was 49.4 years (interquartile range 39.7-61.1), and the main cause of amyloidosis was Familial Mediterranean Fever (37 cases, 43%). Sixteen (18.6%) patients received a biotherapy after transplantation. At 5 years, patient survival was 85.5% (95% confidence interval 77.8-94.0) and 86.2% (80.5-92.2) for cases and controls, respectively (p = 0.5). Death censored graft survival was 78.2% (78.2-93.5) and 91.7% (87.0-96.6), respectively (p = 0.05). Histologically proven AA amyloidosis recurrence was found in 5 patients (5.8%). 55.8% of amyloid patients had at least one infection requiring hospitalization and 27.9% an episode of acute graft rejection. In this group, multivariable analysis showed that CRP concentration at time of transplantation was associated with patient survival (HR 1.01, p = 0.01).
 
 
 
 In this recent cohort, patient survival was comparable to controls and recurrence rates were lower than previously reported. Provided the underlying inflammatory disease is well controlled, patients with AA amyloidosis may be transplanted with similar patient and graft outcomes than that of matched controls.


/pdf/6894-kidney-transplantation-in-patients-with-aa-amyloidosis-17wjmb23.pdf

Sophie georgin Lavialle

Papers

Masitinib for treatment of severely symptomatic indolent systemic mastocytosis: a randomised, placebo-controlled, phase 3 study

#6894 kidney transplantation in patients with aa amyloidosis: a french multi-center matched cohort study in the era of biotherapies