Efficacy and safety of mammalian target of rapamycin inhibitors in systemic mastocytosis: A nationwide French pilot study. - Université de Lille
Article Dans Une Revue American Journal of Hematology Année : 2024

Efficacy and safety of mammalian target of rapamycin inhibitors in systemic mastocytosis: A nationwide French pilot study.

1 Centre d'infectiologie Necker-Pasteur [CHU Necker]
2 CEREMAST - Centre de référence des mastocytoses
3 Imagine - U1163 - Imagine - Institut des maladies génétiques (IHU)
4 Hôpital Necker - Enfants Malades [AP-HP]
5 UPCité - Université Paris Cité
6 CHU Pitié-Salpêtrière [AP-HP]
7 Hôpital Claude Huriez [Lille]
8 CREAK - Centre de référence national des angiœdèmes
9 CHUGA - Centre Hospitalier Universitaire [CHU Grenoble]
10 TIMONE - Hôpital de la Timone [CHU - APHM]
11 CHBA - Centre hospitalier Bretagne Atlantique (Morbihan)
12 Centre Hospitalier Universitaire de Rennes [CHU Rennes] = Rennes University Hospital [Pontchaillou]
13 Hôtel-Dieu de Nantes
14 CHRU Nancy - Centre Hospitalier Régional Universitaire de Nancy
15 Hôpital Saint Eloi [CHU Montpellier]
16 UM - Université de Montpellier
17 CRCM - Centre de Recherche en Cancérologie de Marseille
18 IPC - Institut Paoli-Calmettes
19 CHU Bordeaux
20 CHLS - Centre Hospitalier Lyon Sud [CHU - HCL]
21 CHU Amiens-Picardie
22 CIC 1405 - Centre d'Investigation Clinique [CHU Clermont-Ferrand]
23 CHELTER - Role of intra-Clonal Heterogeneity and Leukemic environment in ThErapy Resistance of chronic leukemias
24 CHU Strasbourg - Centre Hospitalier Universitaire [Strasbourg]
25 CHRU Besançon - Centre Hospitalier Régional Universitaire de Besançon
26 CHU Sud Saint Pierre [Ile de la Réunion]
27 Hôpital Dupuytren [CHU Limoges]
28 CHU de Poitiers [La Milétrie] - Centre hospitalier universitaire de Poitiers = Poitiers University Hospital
29 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
30 CHU Angers - Centre Hospitalier Universitaire d'Angers
31 CHRU Tours - Centre Hospitalier Régional Universitaire de Tours
32 IHBN - Institut d'Hématologie de Basse-Normandie
Antoine Neel

Résumé

Systemic mastocytosis (SM) corresponds to a rare and heterogeneous spectrum of diseases characterized by the accumulation of atypical mast cells (MCs). Advanced mastocytosis (Adv-SM) is associated with poor survival; in contrast, patients with non-advanced SM (non-Adv-SM) usually have a normal life expectancy but may experience poor quality of life. Despite recent therapeutic progress including tyrosine kinase inhibitors, new treatment options are needed for refractory and/or intolerant patients with both severely symptomatic and Adv-SM. In vitro, the mTOR pathway is activated in MCs from patients bearing the KIT D816V mutation. Furthermore, rapamycin induces the apoptosis of KIT D816V MCs selectively. In this nationwide study, we report the outcomes of patients diagnosed with SM and treated with a mammalian target of rapamycin inhibitor (imTOR) within the French National Reference Center for mastocytosis (CEREMAST). All patients registered were relapsing, treatment-refractory, or ineligible for other cytoreductive therapy. Non-Adv-SM patients received imTOR as a monotherapy (rapamycin/everolimus), and Adv-SM patients received imTOR as a monotherapy or in combination with cytarabine. The objective response rate (ORR) in non-Adv-SM was 60% (partial response in 40% and major response in 20%), including reductions in skin involvement, mediator release symptoms, and serum tryptase. In the Adv-SM group, the ORR was 20% (including one major response and one partial response, both in patients with a KIT D816V mutation), which enabled a successful bridge to allogeneic stem cell transplantation in one patient. Our results suggest that imTOR treatment has potential benefits in patients with SM harboring a KIT D816V mutation.
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hal-04691823 , version 1 (09-09-2024)

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Josquin Moraly, Julien Rossignol, Claire Rouzaud, Thomas Gabas, Hassiba Bouktit, et al.. Efficacy and safety of mammalian target of rapamycin inhibitors in systemic mastocytosis: A nationwide French pilot study.. American Journal of Hematology, 2024, American Journal of Hematology, 99 (6), pp.1095-1102. ⟨10.1002/ajh.27323⟩. ⟨hal-04691823⟩
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