-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

1837 Prognostic Characterization of Advanced Mastocytosis Patients Treated with Midostaurin According to Diagnosis and Mutation-Adjusted Risk Score: A Nation-Wide Ceremast Study of 170 Patients

Program: Oral and Poster Abstracts
Session: 634. Myeloproliferative Syndromes: Clinical and Epidemiological: Poster I
Hematology Disease Topics & Pathways:
Diseases, Therapies, therapy sequence, Myeloid Malignancies
Saturday, December 9, 2023, 5:30 PM-7:30 PM

Mael Heiblig1*, Clement Gourguechon2*, Philippe Guilpain3*, Cristina Bulai Livideanu4*, Stéphane Barete, MD, PhD5*, Julie Agopian6*, Fabienne Brenet, PhD7*, Patrice Dubreuil7*, Richard Lemal8*, Olivier Tournilhac9*, Louis Terriou, MD PhD10*, David Launay, Pr11*, Laurence Bouillet, Pr12*, Gandhi Laurent Damaj, MD, PhD13*, Thomas Ballul14*, Céline Greco15*, Laura Polivka, MD, MSc16*, Laurent Frenzel, MD, PhD17*, Cecile Meni18*, Hassiba Bouktit19*, Caroline Gaudy-Marqueste, Pr20*, Marie Gousseff21*, Edwige Le Mouel22*, Antoine Neel, Pr23*, Dana Ranta24*, Roland Jaussaud, Pr25*, Thierry Jo Molina, MD, PhD26*, Julie Bruneau27*, Ludovic Lhermitte28*, Marie Temple29*, Olivier Kosmider, PharmD, PhD30*, Rose-Marie Javier31*, Fabien Pelletier32*, Florence Castelain33*, Frédérique Retornaz34*, Quentin Cabrera35*, Patricia Zunic36*, Marie-Pierre Gourin, MD37*, Ewa Wierzbicka-Hainaut38*, Jean-Francois Viallard, MD PhD39*, Christian Lavigne40*, Cyrille Hoarau41*, Isabelle Durieu42*, Sophie Dimicoli-Salazar43*, Jose-Miguel Torregrosa-Diaz44*, Angele Soria, Pr45*, Michel Arock, Pr46*, Christine Bodemer47*, Olivier Lortholary, Pr48*, Olivier Hermine, MD, PhD49,50 and Julien Rossignol51*

1Hematology Department, Hôpital Lyon Sud, Vourles, Rhône Alpes, France
2Amiens University Hospital, Amiens, France
3Montpellier University Hospital, Montpellier, FRA
4Department of Dermatology, CEREMAST Toulouse, CHU Toulouse, Toulouse, France
5AP-HP, Pitié-salpêtrièRe Hospital, University Pierre & Mari, Paris, France
6Centre De Recherche En CancéRologie De Marseille - AFIRMM, Marseille, FRA
7Oncométabolisme dans les hémopathies malignes, Centre de Recherche en Cancérologie de Marseille, Marseille, France
8Centre hospitalier universitaire de Clermont-Ferrand, Clermont Ferrand, FRA
10Lille University Hospital, Lille, FRA
11Service de médecine interne, CHRU de Lille, Lille, France
12Service de médecine interne, CHU de Grenoble, Grenoble, France
13CHU Caen, Caen, Normandy, FRA
14Service de médecine interne, Hôpital Necker-Enfants Malades, Paris, France
15Douleur et médecine palliative, Hôpital Necker-Enfants Malades, Paris, FRA
16Institut Imagine, Hôpital Necker-Enfants Malades, PARIS, FRA
17Department of Haematology, Institut Necker, Paris, FRA
18AP-HP5, Paris, FRA
19CEREMAST, Hôpital Necker-Enfants Malades, Paris, France
20Service de Dermato Oncologie, Dermatologie Générale et Vénéréologie, Hôpital de la Timone, Marseille, France
21Médecine interne et maladies infectieuses, Centre Hospitalier Bretagne Atlantique, Vannes, France
22Médecine Interne et Immunologie Clinique, Centre Hospitalier Universitaire de Rennes, Rennes, FRA
23Service de Médecine Interne-Médecine Vasculaire, CHU de Nantes, Nantes, France
24Hématologie, CHRU NANCY, Vandoeuvre Les Nancy, FRA
25Service de médecine interne et immunologie clinique, CHRU de Nancy, Vandoeuvre-Les-Nancy, France
26Necker enfants malades, APHP, Paris, Paris, France
27Anatomie pathologique, Hôpital Necker-Enfants Malades, Paris, France
28Laboratory of Onco-Hematology, Necker Enfants-Malades Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP), Université Paris Cité, Paris, France
29Hématologie Biologique, Hôpital Cochin, Paris, France
30Laboratory of Hematology, Université Paris Cité and Assistance Publique-Hôpitaux de Paris. Centre, Hôpital Cochin, Paris, France
31Service de rhumatologie, CHRU Strasbourg, Strasbourg, FRA
32Service de Dermatologie, maladies sexuellement transmissibles, allergologie et explorations cutanées, CHU Besançon, Besançon, France
34Pôle hématologie, infectiologie et médecine interne, Hôpital Européen Marseille, Marseille, France
35Hématologie, CHU Sud Réunion, Saint Pierre, Reunion
36Centre Hospitalier Universitaire de La Réunion - Saint-Pierre, St Pierre, France
37CHU Limoges, Limoges, FRA
38Unité de dermatologie Service de Dermatologie et dermato-allergologi, CHU Poitiers, Poitiers, France
39Service Médecine Interne, Haut-Leveque Hospital, Pessac, France
40Angers University Hospital, Angers, France
41Immunologie, Université de Tours, Tours, FRA
42Service de Médecine Interne, Université De Lyon- Hospices Civils De Lyon, Pierre Benite, France
43Hôpital Haut-Lévêque, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France
44Hématologie, CHU Poitiers, Poitiers, France
45Dermatologie, allergologie et médecine vasculaire, Hôpital Tenon, Paris, France
47Necker Enfant Malades Hospital, University Paris 5, Paris, FRA
48Medecine interne, Hôpital Necker-Enfants Malades, Paris, France
49INSERM U1163 and CNRS 8254, Imagine Institute, Université Sorbonne Paris Cité, Paris, France
50Department of Hematology, Hospital Necker, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France
51Hématologie, NECKER ENFANTS MALADES Hospital APHP, Paris, FRA


Mastocytosis is a spectrum of diseases characterized by the accumulation of atypical mast cells (MC) in tissues. The most frequent form in adult patients is systemic mastocytosis (SM) including indolent SM, bone marrow mastocytosis, smoldering SM and advanced SM (adv-SM). Adv-SM encompasses aggressive SM (ASM), MC leukemia (MCL), SM associated with hematological neoplasms (SM-AHN) and is associated with a poor outcome. Prior the use of tyrosine kinase inhibitors (TKIs), therapeutic options were limited in adv-SM patients. The first TKI developed for adv-SM with KIT D816V mutation was midostaurin, which greatly improved outcomes for patients. However, most patients are primary refractory or relapse early (<12 months) after midostaurin onset. To identify high risk adv-SM patients, a prognostic score the so-called Mutation-Adjusted Risk Score (MARS) have been developed. However, given the heterogeneity of outcomes according to subtype of adv-SM, the identification of high-risk patients within each subtype is critical to optimize therapy. To address this question, we investigated predictive value on outcome of MARS score risk in midostaurin treated Adv-SM patients in a larger group of patients, according to each subtype of adv-SM.


We conducted a nationwide retrospective study of all patients with Adv-SM patients included in the French national mastocytosis reference center registry (CEREMAST). Main inclusion criteria were: (i) adults patients treated with midostaurin in France since 2009 (ii) diagnosis of adv-SM according to WHO 2016 classification (iii) presence of C findings. Patients that have received combination therapy (i.e. azacytidine) or with chronic type of MCL without C finding or lymphoid neoplasm AHN or AML prior midostaurin onset were excluded. Response to midostaurin was assessed according to Valent criteria and MARS score was used to stratify patients into 3 risk groups (high risk, intermediate and low).


Overall, 170 patients treated with midostaurin were identified, including 46 ASM patients, 11 MCL patients and 113 SM-AHN patients. Among SM-AHN patients, chronic myelomonocytic leukemia was the most frequent neoplasm (52%). Response to midostaurin was significantly different regarding subtype of adv-SM (73% in ASM vs 27% in MCL vs 50% in SM-AHN, p=0.006). With a median follow-up of 19 months since midostaurin start, median overall survival (OS) was 69, 9.9 and 32 months (p=0.0013) and time to treatment failure (TTF) was 30, and 3.6 and 9 months in ASM, MCL and SM-AHN (p<0.0001), respectively.

MARS risk group distribution was heterogeneous between ASM, MCL and SM-AHN (p=0.026). In MARS low risk group, median OS was not reached (NR) and 58 months in ASM and SM-AHN respectively (p=0.034, Figure 1). Median OS for both low risk ASM and low risk SM-AHN were significantly different compared with intermediate/high-risk (int/high-risk) groups (NR vs 33 months for ASM, p=0.003 and 58 months vs 24 months, p=0.017). Int/high-risk SM-AHN was the only group with a median OS not significantly different compared with MCL (24 months vs 9 months p=0.266)

Median TTF was 60 months for low risk ASM, 26 months for low risk SM-AHN and only 6.7 months for high/int-risk ASM, 8.4 months for high/int-risk SM-AHN and 3.6 months for MCL.

For the 19 patients who underwent hematopoietic stem cell transplantation (HSCT), median OS was 88 months but did not reach statistical significance compared to non-transplanted patients (47 months, p=0.15). In multivariate analysis, MARS and WHO mastocytosis subtype were the only variables independently associated with OS (figure 2). MARS and midostaurin response were not predictive for both AHN progression and AML transformation in SM-AHN, which occurred in 31% and, 22% of patients respectively. In contrast, presence of portal hypertension/ascites (68% vs 29%, p<0.001) and abnormal karyotype (40 vs 11%, p=0.007) were predictive of AML transformation.


We report herein the largest cohort of adv-SM patients treated with midostaurin. We identified portal hypertension/ascites and karyotype abnormalities as risk factors predictive of AML evolution. Subtype of adv-SM are heterogeneous and, together with MARS, are predictive for both OS and TTF. According to these variables, 5 sub-groups of adv-SM have been identified with different outcomes prompting for specific management.

Disclosures: Heiblig: Jazz Pharmaceuticals: Honoraria; AbbVie: Honoraria; Pfizer Inc.: Honoraria; Astellas: Honoraria; Servier: Honoraria. Livideanu: Lilly, Novartis, UCB: Consultancy; Blueprint Medicines Corporation: Membership on an entity's Board of Directors or advisory committees; ABScience: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding. Barete: Blueprint Medicines Corporation: Consultancy, Other: Fees for symposium and scientific boards; financial support for clinical trials; AbbVie: Other: Fees; Leo Pharma Laboratories: Other: Fees. Damaj: Takeda, Blueprint Medicines Corporation, and Thermo Fisher: Consultancy, Other: Advisory Role; Takeda, AbbVie and Pfizer: Other: Travel and Accommodation Expenses. Frenzel: CSL Berhing: Consultancy, Research Funding; Biomarin: Consultancy; Roche: Consultancy; Pfizer: Consultancy, Other: Grant, Research Funding. Molina: Janssen: Other: Travel and congress fees. Zunic: Abbvie, Janssen, Sanofi: Other: Travel Support. Viallard: EUSAPHARMA: Consultancy. Hermine: AB Science: Consultancy, Other: Shareholder; AB Science, BMS/Celgene, Alexion, Novartis, and Inatherys: Research Funding.

*signifies non-member of ASH