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. 2017 May 3;7:25–35. doi: 10.2147/BLCTT.S87186

Table 1.

Demographic and disease characteristics of patients treated by midostaurin in the CPKC412D2213, CPKC412D2201, and French compassionate use program and of a historical cohort of patients treated before the era of midostaurin

Characteristics (clinical/biological) CPKC412D221351 CPKC412D220129 French TUA compassionate cohort31,a French historical control groupa
Number of patients 26 89 28 44
Male sex, n (%) 15 (57) 57 (64) 24 (85) 27 (61)
Age, median (range) 62 (24–79) 64 (25–82) 67 (29–85)
Age at diagnosis, median (range) na na 65 (12–84) 66 (14–87)
SM subtype according to the WHO, n (%)
 ASM 4 (15) 16 (18) 4 (14) 5 (11)
 SM-AHNMD 20 (77) 57 (64) 18 (64) 33 (75)
 MCL 2 (8) 16 (18) 3 (11) 2 (5)
 MCS 1 (4) 2 (5)
Progressive SSM 2 (7) 2 (5)
C-findings, median (range) All patients had 1 or 2 (1 to ≥3) 2.5 (0–4) 2 (0–4)
C-findings excluding cytopenia more C-findings na 2 (0–3) 1 (0–3)
Hematopoietic organ enlargement,b n (%) na 82 (92) 27 (96) 38 (86)
Urticaria pigmentosa, n (%) na na 13 (46) na
Mast cell mediator symptoms,c (%) na na 13 (46) 26 (59)
Bone marrow mast cell burden, % (range) na 50 (8–98) 35 (10–80) na
Tryptase, median (range) na 236 (27–12,069) 200 (85–2000) 103 (4–900)
Gene mutations, %
 WT c-KIT na 11 3.5 16
 D816V c-KIT 69 87 96.5 84
ASXL1 na na 30 (75% of SM-AHNMD) 19 (85% of SM-AHNMD)
TET2 na na 43 (83% of SM-AHNMD) 29 (70% of SM-AHNMD)
Number of previous therapies – median (range) 1.5 (0–4) 0 (0 to ≥3) 1.5 (1–3) 2 (1–4)
 Steroids, % na 6 21 41
 2-CdA, % na 13 21 49
 Interferon, % na 8 11 8
 TKI other than midostaurin, % na 17 0 13
 Thalidomid, % na na 0 18
 mTOR inhibitor, % na na 11 5
 Other, % na na 0 5
ORRd, % 69 60 71 NA
 Major response 38 45 57
 Partial response 30 15 14
 Stable disease 15 12 11
 Progressive disease 15 11 18
RR%d according to WHO-SM subtype
 ASM na 75 75 NA
 SM-AHNMD na 58 72
 MCL na 50 66
 MCS 0
 Progressive SSM 100
Median treatment duration, months (range) na 11.4 (0.3–51.5) 10.5 (2–32) NA
Median follow-up, months (range) na 26 (12–54) 18.5 (3–36) NA
Median response duration, months (range) na 24.1 (18.1-not estimated) 17 (5–32) NA
Safety/adverse events Any grade % is available (grade 3 and/or 4, % or number if percentage not available) Decreasing frequency: nausea/vomiting (G3, n=2)
Diarrhea
Fatigue (G3, n=2)
Anemia (G3, n=1)
Thrombocytopenia (G3, n=1)
Hyperlipasemia (G3, n=1)
Nausea 79% (6%)
Vomiting 66% (6%)
Diarrhea 54% (8%)
Peripheral edema 34% (4%)
Abdominal pain 28% (3%)
Fatigue 28% (9%)
Constipation 24% (1%)
Headache 23% (2%)
Arthralgia 20% (2%)
Cough 19% (1%)
Dizziness 13%
QT interval prolongation (12%)
Neutropenia 48% (24%)
Anemia 63% (41%)
Thrombocytopenia 52% (29%)
Nausea 89% (39%)
Vomiting 25% (3.5%)
Photosensitivity 25%
Fatigue 14% (3.5%)
Diarrhea 10.5%
Drug-induced toxidermia 3.5% (3.5%)
Peripheral edema 3.5%
Lymphopenia 67%
Cytolytic hepatitis 7%
NA
Discontinuation due to adverse events na 22% 10% NA

Notes: Response rates to midostaurin and safety data.

a

No statistical difference was observed between groups in age at diagnosis, sex, WHO-defined SM subtype distribution,4,5 C-findings, organ enlargement, MCAS, gene mutations distribution, tryptase level, hematological parameters, and follow-up time from diagnosis except for the number of previous treatment lines.

b

Hematopoietic organ enlargement refers to hepatomegaly and/or splenomegaly and/or adenopathy.

c

MCAS was defined by the presence of two symptoms among flush, pruritus, diarrhea, and anaphylactic shock.

d

Response criteria were those of the CPKC412D2201 Phase II trial.

Abbreviations: AHNMD, associated clonal hematological non-mast cell lineage disease; ASM, aggressive systemic mastocytosis; C, clinical; G, grade; MCL, mast cell leukemia; MCS, mast cell sarcoma; mTOR, mammalian target of rapamycin; na, not available; NA, not applicable; ORR, overall response rate; RR, response rate; SM, systemic mastocytosis; SSM, smoldering systemic mastocytosis; TKI, tyrosine kinase inhibitor; TUA, transitory use authorization; WHO, World Health Organization; WT, wild type; 2-CdA, 2-chloro-deoxy-adenosine; MCAS, mast cell activation syndrome.