Disease-modifying therapies in mastocytosis: current recommendations and emerging new treatment approaches
| Diagnosis/disease variant . | Recommended first-line therapy* . | Emerging new treatment options (second- and third-line/future therapies) . |
|---|---|---|
| ISM | No | — |
| SSM | No or cladribine† | Midostaurin in select cases‡ |
| ISM-AHN | AHN-therapy ± HSCT | Midostaurin ± HSCT§ |
| ASM-AHN | AHN-therapy ± HSCT | AHN therapy + midostaurin + HSCT |
| ASM slow | IFN-α, cladribine | Midostaurin ± HSCT |
| ASM rapid | Cladribine, poly-CT, HSCT | Midostaurin + poly-CT + HSCT |
| ASM-t | Cladribine, poly-CT, HSCT | Midostaurin + poly-CT + HSCT |
| cMCL | Cladribine, CT, poly-CT | Midostaurin, CT + midostaurin ± HSCT |
| aMCL | Poly-CT + HSCT | Poly-CT + midostaurin + HSCT |
| MCS | Radiation + poly-CT | Poly-CT + radiation + HSCT |
| ASM/MCL with an imatinib-sensitive target|| | Imatinib | Masitinib, midostaurin|| |
| Diagnosis/disease variant . | Recommended first-line therapy* . | Emerging new treatment options (second- and third-line/future therapies) . |
|---|---|---|
| ISM | No | — |
| SSM | No or cladribine† | Midostaurin in select cases‡ |
| ISM-AHN | AHN-therapy ± HSCT | Midostaurin ± HSCT§ |
| ASM-AHN | AHN-therapy ± HSCT | AHN therapy + midostaurin + HSCT |
| ASM slow | IFN-α, cladribine | Midostaurin ± HSCT |
| ASM rapid | Cladribine, poly-CT, HSCT | Midostaurin + poly-CT + HSCT |
| ASM-t | Cladribine, poly-CT, HSCT | Midostaurin + poly-CT + HSCT |
| cMCL | Cladribine, CT, poly-CT | Midostaurin, CT + midostaurin ± HSCT |
| aMCL | Poly-CT + HSCT | Poly-CT + midostaurin + HSCT |
| MCS | Radiation + poly-CT | Poly-CT + radiation + HSCT |
| ASM/MCL with an imatinib-sensitive target|| | Imatinib | Masitinib, midostaurin|| |
aMCL, acute MCL; cMCL, chronic MCL; MCS, mast cell sarcoma.
These recommendations are based on expert opinion and a few clinical trials published thus far, but are not based on larger controlled clinical trials, which is mainly because of the rarity of the disease.
Cladribine is recommended for a small group of SSM patients suffering from severe (life-threatening) anaphylaxis in whom other treatments failed.
Midostaurin is currently not (yet) approved for treatment of SSM or advanced SM.
Midostaurin may be considered in these patients when the AHN component of the disease expresses a clinically relevant drug target (KIT D816V or FLT3 ITD).
Imatinib-sensitive targets detected in ASM/MCL include WT KIT, rare mutant forms of KIT, and PDGFRA/B mutants. These mutants are also sensitive against masitinib and midostaurin.