For:
Newly Diagnosed FLT3+ Acute Myeloid Leukemia (AML)
Important Safety Information:

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…

See More

Indication: RYDAPT is indicated, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation–positive, as detected by an FDA-approved test.

Limitations of Use
RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML.

Efficacy

Overall Survival

RYDAPT® (midostaurin) CAPSULES: Significant and sustained survival benefits for patients with newly diagnosed FLT3+ AML

Overall Survival Overall Survival
  • Because survival curves plateaued before reaching the median, median survival could not be reliably estimated1
  • OS was measured from the date of randomization until death by any cause1

Event-Free Survival

Greater EFS with RYDAPT plus standard chemotherapy vs standard chemotherapy plus placebo1

Event-Free Survival 60 days Image Event-Free Survival 60 days Image
  • An EFS event was defined as a failure to obtain a complete remission (CR) within 60 days of initiation of protocol therapy, relapse, or death from any cause1

Event-Free Survival Anytime Event-Free Survival Anytime
  • An exploratory analysis of EFS, defined as a failure to obtain a CR anytime during induction, relapse, or death from any cause, with failures assigned as an event on study day 11

Trial Design

RATIFY was the largest clinical trial conducted with patients with newly diagnosed FLT3+ AML

RATIFY was a phase 3, randomized, double-blind, placebo-controlled study performed in partnership with the Alliance for Clinical Trials in Oncology1,2

Efficacy Trial Design Efficacy Trial Design

*Transplantation was allowed but not specifically mandated per study protocol. Patients who proceeded to hematopoietic stem cell transplantation (SCT) stopped receiving study treatment, but all patients were followed for survival.1

Efficacy and safety were evaluated through all phases of the study1,2
  • Included in the study were 717 adults with newly diagnosed FLT3+ AML1
  • RYDAPT plus standard cytarabine and daunorubicin induction and high-dose cytarabine consolidation chemotherapy was compared with standard chemotherapy plus placebo, followed by continuous RYDAPT or placebo treatment according to initial assignment for up to 12 additional 28-day cycles1
    • A second course of induction was administered to 25% of patients, 62% initiated at least 1 cycle of consolidation, 29% initiated maintenance, and 17% completed all 12 planned cycles of maintenance; 21% of patients underwent SCT in first CR
  • The primary end point in RATIFY was OS, which was measured from the date of randomization until death by any cause1
  • The primary analysis was conducted after a minimum follow-up of approximately 3.5 years following randomization of the last patient1
  • Secondary end points included EFS and the toxicity of RYDAPT plus chemotherapy1,2
  • Patients with acute promyelocytic leukemia or therapy-related AML were not eligible1
  • Patients in the pivotal study were not re-randomized at the start of postconsolidation treatment and, therefore, there is no assessment of the efficacy of RYDAPT in this stage alone1
  • The overall rate of SCT (induction failure, first CR, or salvage after relapse) was 59% (214/360) of patients in the RYDAPT plus standard chemotherapy arm vs 55% (197/357) in the placebo plus standard chemotherapy arm1

Treatment Phases

Changing the treatment paradigm in AML

Mutation testing and combination treatment with RYDAPT can help improve OS for patients with newly diagnosed FLT3+ AML1,3
  • 23% reduction in the risk of death compared with standard chemotherapy plus placebo: HR=0.77 (95% CI, 0.629-0.953), P=.0161

Treatment Phases Treatment Phases

 

FLT3 mutation testing is performed by The Laboratory for Personalized Molecular Medicine, a subsidiary of Invivoscribe Technologies, Inc., which has gained FDA approval for its FLT3 test as a companion diagnostic for RYDAPT in newly diagnosed FLT3+ AML. Laboratory for Personalized Molecular Medicine® is a registered trademark of Invivoscribe Technologies, Inc.

bid, twice daily; EFS, event-free survival; FLT3, FMS-like tyrosine kinase 3; ITD, internal tandem duplication; OS, overall survival; TKD, tyrosine kinase domain.

References:
  1. Rydapt [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2018.
  2. Data on file. Study no. CPKC412A2301. Novartis Pharmaceuticals Corp; 2016.
  3. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Acute Myeloid Leukemia V.3.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed May 16, 2019. To view the most recent and complete version of the guideline, go online to NCCN.org.
  4. Patel JP, Gönen M, Figueroa ME, et al. Prognostic relevance of integrated genetic profiling in acute myeloid leukemia. N Engl J Med. 2012;366(12):1079-1089.
  5. De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016;6(7):e441.

INDICATION for RYDAPT® (midostaurin) capsules

Acute Myeloid Leukemia
RYDAPT is indicated, in combination with standard cytarabine and daunorubicin induction and cytarabine consolidation chemotherapy, for the treatment of adult patients with newly diagnosed acute myeloid leukemia (AML) who are FLT3 mutation–positive, as detected by an FDA-approved test.

Limitations of Use
RYDAPT is not indicated as a single-agent induction therapy for the treatment of patients with AML.

IMPORTANT SAFETY INFORMATION for RYDAPT® (midostaurin) capsules

CONTRAINDICATIONS
  • Do not use in patients with hypersensitivity to midostaurin or its excipients. Hypersensitivity reactions have included anaphylactic shock, dyspnea, flushing, chest pain, and angioedema
WARNINGS AND PRECAUTIONS
Embryofetal Toxicity
  • Do not use during pregnancy. Midostaurin caused severe embryofetal 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://psi.novartis.com
Pulmonary Toxicity
  • 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
ADDITIONAL CONSIDERATIONS
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
Infertility
  • 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
Drug Interactions
  • Strong CYP3A4 Inducers: Avoid concomitant use as strong CYP3A4 inducers decrease exposure to midostaurin and may reduce efficacy
  • Strong CYP3A4 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
ADVERSE REACTIONS
Acute Myeloid Leukemia
  • Most common adverse reactions (≥20%) were febrile neutropenia (83%), nausea (83%), mucositis (66%), vomiting (61%), headache (46%), petechiae (36%), musculoskeletal pain (33%), epistaxis (28%), device-related infection (24%), hyperglycemia (20%), and upper respiratory tract infection (20%)
  • Most frequent grade 3/4 adverse reactions (≥10%) were febrile neutropenia (84%), device-related infection (16%), and mucositis (11%)
  • Most common (≥10%) lab abnormalities were alanine aminotransferase increase (71%), hypernatremia (21%), and hypocalcemia (74%)

Please see full Prescribing Information for RYDAPT® (midostaurin) capsules.