Table 1.
Overview of main tyrosine-kinase inhibitor drugs investigated in patients with advanced systemic mastocytosis.
| TKI | Number of AdvSM reported (ref) | Activity in SM | Activity in KIT D816V | Current status |
|---|---|---|---|---|
| Imatinib | 32 (Lim et al., 2009; Vega-Ruiz et al., 2009; Alvarez-Twose et al., 2017) | High in sensitive mutations (KIT outside exon 17 or PDGFR) | - | FDA approved for Adult patients ASM without the D816V KIT or unknown KIT mutational status |
| Nilotinib | 44 (Hochhaus et al., 2015) | Low | -/+ | Inactive |
| Dasatinib | 19 (Purtill et al., 2008; Verstovsek et al., 2008) | Low | - | Inactive |
| Masitinib | – | Modest in ISM with related handicap | - | Under investigation in phase 3 trials in severe ISM and SSM with related handicap |
| Midostaurin | 142 (Gotlib et al., 2016; DeAngelo et al., 2018) | High (60-69% ORR) | ++ | Approved by the FDA and the EMA for AdvSM |
| Avapritinib | 24 (Deininger et al., 2018) | High (83% ORR) | +++ | Under investigation in phase 2 trials in AdvSM and in ISM and SSM with bad symptom control |
ASM, aggressive systemic mastocytosis; ISM, indolent systemic mastocytosis; SSM, smouldering systemic mastocytosis; ORR, overall rate response.