CONTRAINDICATIONS
Do not use in patients with hypersensitivity to midostaurin or its excipients. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioed…
Efficacy
In this short video, Dr Bart Scott talks about RYDAPT® (midostaurin) capsules for the Treatment of Advanced Systemic Mastocytosis*
In this short video, Bart Scott, MD, Associate Member, Transplantation Program Clinical Research Division from the Fred Hutchinson Cancer Research Center in Seattle, Washington, talks about the efficacy and safety of RYDAPT® (midostaurin) capsules for the treatment of advanced systemic mastocytosis, or advanced SM.
In this video, Dr Scott outlines
- The design of the studies used to assess the efficacy and safety of RYDAPT
- The parameters used to exclude patients
- The evaluable attributes of patients included in the study
- How efficacy was evaluated and the criteria used
- The different response levels amongst different subtypes
Dr Scott then goes on to describe how RYDAPT was also assessed as a post-hoc exploratory analysis.1
Finally Dr Scott talks about adverse reactions (Grades 1/2), serious adverse reactions (Grades 3/4), discontinuation of treatment, and on-treatment deaths.
Dr Scott received compensation from Novartis Pharmaceuticals Corporation for participation in this program.
*Aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN) and mast cell leukemia (MCL) are collectively referred to as advanced SM.
Trial Design
Prescribe the First FDA-Approved Treatment for Adults With Advanced SM Including the D816V Mutant c-KIT
Demonstrated measurable reductions in organ damage for adult patients with advanced SM from study D22011
- A multicenter, single-arm, phase 2 study in 116 patients with advanced SM
- 89 patients were identified who had measurable C-findings and were evaluable for response
- 16 patients had aggressive systemic mastocytosis (ASM)
- 57 patients had systemic mastocytosis with an associated hematological neoplasm (SM-AHN)
- 16 patients had mast cell leukemia (MCL)
- Patients received RYDAPT 100 mg orally twice daily in 28-day cycles until disease progression or intolerable toxicity1
- Efficacy was established on the basis of confirmed complete remission (CR) plus incomplete remission (ICR) by six 28-day cycles of oral RYDAPT 100 mg twice daily by modified Valent criteria for ASM and SM-AHN1
Baseline patient characteristics1
- The study enrolled 116 adult patients with relapse or progression to 0, 1, or 2 prior regimens for SM
- Among these patients, 36% had prior therapy for SM, and 82% had the KIT D816V mutation detected at baseline
- The study excluded patients with serum creatinine >2.0 mg/dL, hepatic transaminases >2.5 x ULN or >5 x ULN if disease-related, total bilirubin >1.5 x ULN or >3 x ULN if disease-related, QTc >450 msec, cardiovascular disease including left ventricular ejection fraction <50%, any pulmonary infiltrates, or acute-stage or life-threatening AHN
IN ALL PATIENTS EVALUATED* (N=89):
21% CR + ICR by 6 cycles (95% CI: 13%-31%) (n=19)†,‡
0.5 months median time to CR + ICR (Range: 0.1-3.0)
Median duration of CR + ICR was not reached§ (95% CI: 24.1-NE; Range||: 6.6+, 65.8+)

Response Rates
Modified Valent criteria3
COMPLETE REMISSION (CR)
- ≥1 C-finding resolved
- No mast cell infiltrate in organ
- No organomegaly
- Serum tryptase decreased to <20 ng/mL
INCOMPLETE REMISSION (ICR)
- ≥1 C-finding resolved
- >50% decrease in mast cell infiltrate in organ
- >50% decrease in organomegaly
- >50% decrease in serum tryptase
RYDAPT – the largest study ever conducted in advanced SM, including all 3 subtypes1
36% of patients had prior therapy for SM1
82% of patients had the KIT D816V mutation detected at baseline1
Efficacy in the RYDAPT pivotal study (D2201) was established on the basis of CR plus ICR by six 28-day cycles of oral RYDAPT 100 mg twice daily by modified Valent criteria for ASM and SM-AHN.1
In the RYDAPT supportive study, efficacy was evaluated by the Valent criteria.1
Response rates by mutation status and prior therapy
63% – 46 of 73 patients with a documented KIT D816V mutation had confirmed major or partial responses with RYDAPT1
65% – 21 of 32 patients with prior therapy for SM had confirmed major or partial responses1
44% – 7 of 16 patients with wild-type or unknown KIT D816V mutation status had confirmed major or partial reponses1
- Major response was defined as the complete resolution of 1 or more clinical finding (measurable organ damage related to mastocytosis)3,4
- Partial response was defined as a >50% improvement in 1 or more clinical finding (good partial response) or a >20% to ≤50% improvement in 1 or more clinical finding (minor partial response)3,4
Footnotes:
NE, not estimated.
*25 patients were not assessable for the presence of MCL on central histopathology review, and 11 patients with unconfirmed presence of an AHN were regarded as not having AHN.
†Per study steering committee. Response confirmation after ≥8 weeks was required. No CRs were reported.
‡ Patients who received concomitant high-dose corticosteroids were considered unevaluable and were excluded from the response assessment.
§Among patients with response of CR or ICR, the estimated median follow-up for duration of response was 35.4 months overall.
||A + sign indicates a censored value. Most common adverse events in the advanced SM studies1
- Rydapt [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2021.
- Arock M, Akin C, Hermine O, Valent P. Current treatment options in patients with mastocytosis: status in 2015 and future perspectives. Eur J Haematol. 2015;94(6):474-490.
- Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis. N Engl J Med. 2016;374(26):2530-2541.
- Gotlib J, Kluin-Nelemans HC, George TI, et al. Efficacy and safety of midostaurin in advanced systemic mastocytosis [supplementary appendix]. N Engl J Med. 2016;374(26):2530-2541.
INDICATION for RYDAPT® (midostaurin) capsules
Systemic Mastocytosis
RYDAPT is indicated for the treatment of adult patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL).
IMPORTANT SAFETY INFORMATION for RYDAPT® (midostaurin) capsules
- Do not use in patients with hypersensitivity to midostaurin or its excipients. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema
Embryo-Fetal Toxicity
- Do not use during pregnancy. Midostaurin caused severe embryo-fetal abnormalities and death in animal studies
- Verify pregnancy status of females of reproductive potential within 7 days prior to initiating RYDAPT
- Advise females of reproductive potential to use effective contraception during treatment and for at least 4 months after the last dose
- Males taking RYDAPT should use effective contraception with females of reproductive potential and pregnant women and for at least 4 months after the last dose
- Pregnancy exposure registry to monitor pregnancy outcomes: Females who may have been exposed to RYDAPT during pregnancy, directly or through a male partner receiving RYDAPT, should contact Novartis Pharmaceuticals Corporation at 1-888-669-6682 and/or at https://report.novartis.com
- Cases of interstitial lung disease and pneumonitis, some fatal, have occurred in patients treated with RYDAPT as monotherapy or with chemotherapy
- Monitor patients for pulmonary symptoms. Discontinue RYDAPT in patients who experience signs or symptoms of interstitial lung disease or pneumonitis without an infectious etiology
- Prolonged (≥44 days) grade 4 neutropenia and thrombocytopenia were reported in 2 pediatric patients with FLT3 mutation-positive AML treated with midostaurin and combination chemotherapy. An azole antifungal (a strong CYP3A4 inhibitor) was coadministered which may increase midostaurin concentrations and risk of toxicity
- The safety and effectiveness of RYDAPT in pediatric patients have not been established
Lactation
- Because of the potential for serious adverse reactions in breastfed infants from RYDAPT, advise women not to breastfeed during treatment with RYDAPT and for at least 4 months after the last dose
- Based on findings in animals, RYDAPT may impair fertility in females and males of reproductive potential. It is unknown whether these effects on fertility are reversible
- Strong CYP3A Inducers: Avoid concomitant use as strong CYP3A4 inducers decrease exposure to midostaurin and may reduce efficacy
- Strong CYP3A Inhibitors: Coadministration with strong CYP3A4 inhibitors may increase midostaurin concentrations and may increase the risk of toxicity. Monitor patients for increased risk of adverse reactions, especially during the first week of RYDAPT use in each chemotherapy cycle and the first week of consecutive RYDAPT administration. Consider alternative therapies that do not strongly inhibit CYP3A4 activity
- CYP2B6, BCRP, OATP1B1 Substrates: RYDAPT decreased the systemic exposure of a sensitive CYP2B6 substrate. Coadministration of RYDAPT increased the exposure of a breast cancer resistance protein (BCRP) and organic anion transporter polypeptide (OATP)1B1 substrate. Dose adjustments for coadministered CYP2B6, BCRP, or OATP1B1 substrates may be necessary with RYDAPT
Aggressive Systemic Mastocytosis (SM), SM With Associated Hematologic Neoplasm, Mast Cell Leukemia
- Most common adverse reactions (≥20%) excluding laboratory terms were nausea (82%), vomiting (68%), diarrhea (54%), edema (40%), musculoskeletal pain (35%), abdominal pain (34%), fatigue (34%), upper respiratory tract infection (30%), constipation (29%), pyrexia (27%), headache (26%), and dyspnea (23%)
- Grade ≥3 adverse reactions (≥5%) excluding laboratory terms were fatigue (9%), sepsis (9%), gastrointestinal hemorrhage (9%), pneumonia (8%), diarrhea (8%), febrile neutropenia (8%), edema (7%), dyspnea (7%), nausea (6%), vomiting (6%), abdominal pain (6%), and renal insufficiency (5%)
- Most common (≥10%) nonhematologic grade ≥3 laboratory abnormalities were hyperglycemia (nonfasting) (18%), lipase increase (18%), and hyperuricemia (11%)
- Most common (≥20%) hematologic grade ≥3 laboratory abnormalities were lymphopenia (42%), anemia (38%), thrombocytopenia (27%), and neutropenia (22%)
Please see full Prescribing Information for RYDAPT® (midostaurin) capsules.
*Aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL) are collectively referred to as advanced systemic mastocytosis (SM).