TY - JOUR
T1 - Efficacy and safety of midostaurin in patients with advanced systemic mastocytosis
T2 - 10-year median follow-up of a phase II trial
AU - DeAngelo, D. J.
AU - George, T. I.
AU - Linder, A.
AU - Langford, C.
AU - Perkins, C.
AU - Ma, J.
AU - Westervelt, P.
AU - Merker, J. D.
AU - Berube, C.
AU - Coutre, S.
AU - Liedtke, M.
AU - Medeiros, B.
AU - Sternberg, D.
AU - Dutreix, C.
AU - Ruffie, P. A.
AU - Corless, C.
AU - Graubert, T. J.
AU - Gotlib, J.
N1 - Publisher Copyright:
© 2018 Macmillan Publishers Limited, part of Springer Nature.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - Patients with advanced systemic mastocytosis (SM) (e.g. aggressive SM (ASM), SM with an associated hematologic neoplasm (SMAHN) and mast cell leukemia (MCL)) have limited treatment options and exhibit reduced survival. Midostaurin is an oral multikinase inhibitor that inhibits D816V-mutated KIT, a primary driver of SM pathogenesis. We conducted a phase II trial of midostaurin 100 mg twice daily, administered as 28-day cycles, in 26 patients (ASM, n = 3; SM-AHN, n = 17; MCL, n = 6) with at least one sign of organ damage. During the first 12 cycles, the overall response rate was 69% (major/partial response: 50/19%) with clinical benefit in all advanced SM variants. With ongoing therapy, 2 patients achieved a complete remission of their SM. Midostaurin produced a ≥ 50% reduction in bone marrow mast cell burden and serum tryptase level in 68% and 46% of patients, respectively. Median overall survival for the entire cohort was 40 months, and 18.5 months for MCL patients. Low-grade gastrointestinal side effects were common and manageable with antiemetics. The most frequent grade 3/4 nonhematologic and hematologic toxicities were asymptomatic hyperlipasemia (15%) and anemia (12%). With median follow-up of 10 years, no unexpected toxicities emerged. These data establish the durable activity and tolerability of midostaurin in advanced SM.
AB - Patients with advanced systemic mastocytosis (SM) (e.g. aggressive SM (ASM), SM with an associated hematologic neoplasm (SMAHN) and mast cell leukemia (MCL)) have limited treatment options and exhibit reduced survival. Midostaurin is an oral multikinase inhibitor that inhibits D816V-mutated KIT, a primary driver of SM pathogenesis. We conducted a phase II trial of midostaurin 100 mg twice daily, administered as 28-day cycles, in 26 patients (ASM, n = 3; SM-AHN, n = 17; MCL, n = 6) with at least one sign of organ damage. During the first 12 cycles, the overall response rate was 69% (major/partial response: 50/19%) with clinical benefit in all advanced SM variants. With ongoing therapy, 2 patients achieved a complete remission of their SM. Midostaurin produced a ≥ 50% reduction in bone marrow mast cell burden and serum tryptase level in 68% and 46% of patients, respectively. Median overall survival for the entire cohort was 40 months, and 18.5 months for MCL patients. Low-grade gastrointestinal side effects were common and manageable with antiemetics. The most frequent grade 3/4 nonhematologic and hematologic toxicities were asymptomatic hyperlipasemia (15%) and anemia (12%). With median follow-up of 10 years, no unexpected toxicities emerged. These data establish the durable activity and tolerability of midostaurin in advanced SM.
UR - http://www.scopus.com/inward/record.url?scp=85042230675&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042230675&partnerID=8YFLogxK
U2 - 10.1038/leu.2017.234
DO - 10.1038/leu.2017.234
M3 - Article
C2 - 28744009
AN - SCOPUS:85042230675
SN - 0887-6924
VL - 32
SP - 470
EP - 478
JO - Leukemia
JF - Leukemia
IS - 2
ER -