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.
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.
Hematopoietic organ enlargement refers to hepatomegaly and/or splenomegaly and/or adenopathy.
MCAS was defined by the presence of two symptoms among flush, pruritus, diarrhea, and anaphylactic shock.
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.