Comparison of prognostic scores according to WHO classification in 170 patients with advanced mastocytosis and C‐finding treated with midostaurin

• Published in: American journal of hematology Vol. 99; no. 11; pp. 2127 - 2139
• Main Authors: Heiblig, Maël, Gourguechon, Clément, Guilpain, Philippe, Bulai‐Livideanu, Cristina, Barete, Stéphane, Chantran, Yannick, Agopian, Julie, Brenet, Fabienne, Dubreuil, Patrice, Lespinasse, Jérémie, Lemal, Richard, Tournilhac, Olivier, Terriou, Louis, Launay, David, Bouillet, Laurence, Chatain, Catharina, Damaj, Ghandi, Ballul, Thomas, Greco, Celine, Polivka, Laura, Frenzel, Laurent, Meni, Cécile, Bouktit, Hassiba, Benabou, Dina, Gaudy‐Marqueste, Caroline, Gousseff, Marie, Le Mouel, Edwige, Neel, Antoine, Ranta, Dana, Jaussaud, Roland, Molina, Thierry Jo, Bruneau, Julie, Villarese, Patrick, Lhermitte, Ludovic, Maouche‐Chrétien, Leila, Temple, Marie, Kosmider, Olivier, Javier, Rose‐Marie, Pelletier, Fabien, Castelain, Florence, Retornaz, Frederique, Cabrera, Quentin, Zunic, Patricia, Gourin, Marie Pierre, Wierzbicka–Hainaut, Ewa, Viallard, Jean François, Lavigne, Christian, Hoarau, Cyrille, Durieu, Isabelle, Dimicoli‐Salazar, Sophie, Torregrosa‐Diaz, Jose Miguel, Wemeau, Mathieu, Soria, Angèle, Arock, Michel, Bodemer, Christine, Lortholary, Olivier, Hermine, Olivier, Rossignol, Julien
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.11.2024; Wiley Subscription Services, Inc; Wiley
• Subjects: Adult; Aged; Aged, 80 and over; Blood cancer; Female; Hematologic Neoplasms - drug therapy; Hematologic Neoplasms - mortality; Humans; Leukemia, Mast-Cell - drug therapy; Life Sciences; Male; Mast cell leukemia; Mastocytosis; Mastocytosis, Systemic - classification; Mastocytosis, Systemic - diagnosis; Mastocytosis, Systemic - drug therapy; Mastocytosis, Systemic - mortality; Middle Aged; Prognosis; Protein Kinase Inhibitors - therapeutic use; Retrospective Studies; Staurosporine - analogs & derivatives; Staurosporine - therapeutic use; World Health Organization
• ISSN: 0361-8609; 1096-8652; 1096-8652
• DOI: 10.1002/ajh.27478

Advanced systemic mastocytosis (AdvSM) encompasses heterogeneous mastocytosis subtypes and is associated with poor outcomes. Although midostaurin was the first tyrosine kinase inhibitor to be approved for AdvSM patients, long‐lasting responses are limited. The mutation‐Adjusted Risk Score (MARS), the International Prognostic Scoring System for mastocytosis (IPSM) and the Global Prognostic Score for Systemic Mastocytosis (GPSM) have been established to characterize the outcomes of patients with overall AdvSM. However, given the outcome's dependency on the AdvSM subtype, prognostic characterization within each subtype is critical. We aimed to study the predictive ability using Harrell's concordance index of prognostic scores according to the AdvSM subtype. We conducted a nationwide retrospective study using the French mastocytosis reference center's registry and included all midostaurin‐treated patients with C finding. Overall, 170 patients were identified: 46 aggressive SM (ASM), 11 mast cell leukemia (MCL), and 113 SM with associated hematological neoplasm (SM‐AHN). All risk scores improved their discriminative value for overall survival (OS) when combined with the AdvSM subtype. The best predictive value was for adjusted MARS (C‐index = 0.689), followed by GPSM (C‐index = 0.677) and IPSM (C‐index = 0.618). In a multivariable analysis, MARS stratification and the AdvSM subtype were both prognostic for OS. Accordingly, five subgroups of patients with AdvSM and a different median OS were identified: 9.9 months for MCL, 24 months for intermediate/high‐risk SM‐AHN, 33 months for intermediate/high‐risk ASM, 58 months for low‐risk SM‐AHN and was not reached for low‐risk ASM (p < 0.001). The AdvSM subtype and the MARS are the most predictive of OS and should prompt specific management. The AdvSM subtypecombined with the MARS score has the best prognostic value for overall survivalin patients with AdvSM and at least one C‐finding treated with midostaurin. Thus,five subgroups of AdvSM patients with different outcomes are identified. Thepresence of an abnormal karyotype or portal hypertension is associated with therisk of AML transformation in patients with SM‐AHN.