AYVAKIT® (avapritinib) resources for you
and your patients with Advanced SM
and your patients with Advanced SM
Dr Ruben Mesa from MD Anderson Cancer Center discusses the journey from suspecting Advanced SM to making a diagnosis.
Dr Ruben Mesa from MD Anderson Cancer Center reviews information about the efficacy and safety of AYVAKIT, as demonstrated in the PATHFINDER and EXPLORER clinical trials.
Dr James McCloskey from Hackensack Meridian Health reviews information about managing patients who have started treatment with AYVAKIT.
POPUP 1 : CONTENT HERE
POPUP 2 : CONTENT HERE
POPUP 3 : CONTENT HERE
Dr Ruben Mesa from MD Anderson Cancer Center discusses the journey from suspecting Advanced SM to making a diagnosis.
TranscriptDr Ruben Mesa from MD Anderson Cancer Center reviews information about the efficacy and safety of AYVAKIT, as demonstrated in the EXPLORER and PATHFINDER clinical trials.
TranscriptDr James McCloskey from Hackensack Meridian Health reviews information about managing patients who have started treatment with AYVAKIT.
TranscriptVideo Transcript
Suspecting and Diagnosing Advanced Systemic Mastocytosis (SM)
Dr Mesa Voice-over:
Hello. I’m Dr Ruben Mesa, and in this video, we’re talking about suspecting and diagnosing Advanced Systemic Mastocytosis.
Advanced Systemic Mastocytosis (or Advanced SM) is a clonal mast cell neoplasm caused by the KIT D816V mutation in approximately 95% of cases.
People living with Advanced SM can experience significant symptom burden, including organ damage, and impact on their quality of life.
Patients with Advanced SM may also have shortened overall survival.
In fact, one study showed that the median overall survival was 3.5 years for patients with aggressive systemic mastocytosis (or ASM), 2 years for patients with systemic mastocytosis with an associated hematological neoplasm (or SM-AHN), and less than 6 months for patients with mast cell leukemia (or MCL).
So, the sooner Advanced SM can be diagnosed, the sooner we can determine if treatment may be appropriate for our patients.
The challenge to diagnosing Advanced SM comes from its symptoms. They can be heterogeneous or nonspecific, so one patient may end up presenting to many different healthcare specialists, which can prolong a diagnosis.
In fact, the median time from symptom onset to diagnosis for patients with Advanced SM is generally around 3 years.
Knowing the symptoms of Advanced SM may help shorten a patient’s time to diagnosis.
Common mast cell mediator symptoms of Advanced SM include maculopapular rash, gastrointestinal distress, and life-threatening anaphylaxis. Additionally, patients can experience organ damage and related symptoms, as shown here.
Accurately diagnosing Advanced SM is a multistep process.
The diagnostic workup for suspected Advanced SM includes a bone marrow biopsy with mast cell immunophenotyping, a serum tryptase test, and KIT D816V mutation testing.
Advanced SM may be overlooked or missed in some patients with suspected myeloid neoplasms.
Knowing this, an incidental KIT mutation finding should prompt a full diagnostic workup.
Generally, in patients where Advanced SM is suspected, it is recommended to perform high-sensitivity KIT D816V testing, which refers to assays with sensitivities of less than 1%. Next- generation sequencing panels can exhibit low sensitivity and fail to detect KIT D816V.
Looking at the diagnostic criteria for SM, the World Health Organization (or WHO) requires presence of 1 major criterion AND at least 1 minor criterion—OR, in the absence of 1 major criterion, presence of at least 3 minor criteria is sufficient to make a diagnosis.
Additionally, for an Advanced SM diagnosis, criteria for one of the three subtypes must be met.
I want to thank you for your time. You can find all this information and more at AYVAKIT.com/HCP.
Please take a moment to familiarize yourselves with the Important Safety Information associated with AYVAKIT.
Important Safety Information Voice-over:
AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with Advanced SM including patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia.
Limitations of Use: AYVAKIT is not recommended for the treatment of patients with Advanced SM with platelet counts of less than 50,000 per microliter.
IMPORTANT SAFETY INFORMATION
There are no contraindications for AYVAKIT.
Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in less than 1% of patients. Overall, ICH (for example, subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT. In Advanced SM patients who received AYVAKIT at 200 milligrams daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts greater than or equal to 50,000 per microliter prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts. Monitor patients closely for risk of ICH including those with thrombocytopenia, vascular aneurysm or a history of ICH or cerebrovascular accident within the prior year. Permanently discontinue AYVAKIT if ICH of any grade occurs. A platelet count must be performed prior to initiating therapy.
AYVAKIT is not recommended in Advanced SM patients with platelet counts less than 50,000 per microliter. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks. After 8 weeks of treatment, monitor platelet counts every 2 weeks or as clinically indicated based on platelet counts. Manage platelet counts of less than 50,000 per microliter by treatment interruption or dose reduction.
Cognitive adverse reactions can occur in patients receiving AYVAKIT. Cognitive adverse reactions occurred in 39% of 749 patients and in 28% of 148 SM patients (3% were greater than Grade 3). Memory impairment occurred in 16% of patients; all events were Grade 1 or 2. Cognitive disorder occurred in 10% of patients; less than 1% of these events were Grade 3. Confusional state occurred in 6% of patients; less than 1% of these events were Grade 3. Other events occurred in less than 2% of patients. Depending on the severity, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.
AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks after the final dose.
The most common adverse reactions (greater than or equal to 20%) were edema, diarrhea, nausea, and fatigue/asthenia.
Avoid coadministration of AYVAKIT with strong and moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong and moderate CYP3A inducers.
To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see the full Prescribing Information for AYVAKIT at AYVAKIT.com/HCP.
Video Transcript
About AYVAKIT
Dr Mesa Voice-over:
Hi, I’m Dr Ruben Mesa and today we are talking about avapritinib, commercially known as AYVAKIT, which is indicated for the treatment of adult patients with Advanced Systemic Mastocytosis (or Advanced SM) including patients with aggressive systemic mastocytosis (or ASM), systemic mastocytosis with an associated hematologic neoplasm (or SM-AHN), and mast cell leukemia (or MCL).
AYVAKIT is not recommended for the treatment of patients with Advanced SM with platelet counts of less than 50,000 per microliter.
Warnings and precautions for AYVAKIT include intracranial hemorrhage (or ICH), cognitive effects, and embryo-fetal toxicity.
AYVAKIT is the only targeted therapy for Advanced SM designed for potent and selective inhibition of KIT D816V, which is the primary driver of Advanced SM in approximately 95% of cases.
AYVAKIT was studied in the EXPLORER and PATHFINDER clinical trials, which were 2 multicenter, single-arm, open-label clinical trials designed to evaluate the safety and efficacy of AYVAKIT in adult patients with a confirmed diagnosis of Advanced SM per World Health Organization (or WHO) criteria.
Patients in EXPLORER received a starting dose ranging from 30 milligrams to 400 milligrams—orally, once daily. Patients in PATHFINDER were enrolled at a starting dose of 200 milligrams—orally, once daily.
Efficacy of AYVAKIT in patients with Advanced SM was based on an overall response rate (or ORR) in 53 patients dosed up to 200 milligrams daily, per modified IWG-MRT-ECNM criteria, with a median follow-up of 11.6 months. In the subgroup of patients with MCL, the efficacy of AYVAKIT was based on complete remission.
Safety was also assessed, which we'll cover in a bit.
Looking at patient demographics at baseline—the KIT D816V mutation was detectable by droplet digital polymerase chain reaction in 94% of patients in the trial. And 66% had received prior antineoplastic therapy.
3.8% of patients had ASM, 75.5% of patients had SM-AHN, and 20.7% of patients had MCL.
Serious ICH may occur with AYVAKIT treatment. Overall, ICH occurred in 2.9% of 749 patients who received AYVAKIT.
Permanently discontinue AYVAKIT if ICH occurs.
Important Safety Information Voice-over:
Fatal events occurred in less than 1% of patients.
In Advanced SM patients who received AYVAKIT at 200 milligrams daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts greater than or equal to 50,000 per microliter prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts.
Monitor patients closely for risk of ICH including those with thrombocytopenia, vascular aneurysm or a history of ICH or cerebrovascular accident within the prior year.
Dr Mesa Voice-over:
In clinical trials, response-evaluable patients included those with a confirmed diagnosis of Advanced SM per WHO criteria, as well as those who, at baseline, were deemed evaluable by modified IWG-MRT-ECNM criteria.
Patients must also have received at least 1 dose of AYVAKIT, had at least 2 post-baseline bone marrow assessments, and were on study for at least 24 weeks or had an end-of-study visit.
In clinical trials, AYVAKIT has shown proven efficacy and demonstrated duration of response in Advanced SM.
Results show a 57% ORR across 53 evaluable Advanced SM patients who were dosed up to 200 milligrams daily. A 72% ORR was achieved with the addition of 15% of patients who had a clinical improvement. 28% of patients had complete remission with or without partial hematologic recovery.
The median duration of response was 38.3 months, and this duration of response was driven primarily by SM-AHN patients.
The median time to response was 2.1 months, and the median time to complete remission with or without partial hematologic recovery was 9.2 months.
Looking closer at each of the 3 subtypes, amongst patients with MCL, the ORR was 45%.
In SM-AHN, the ORR was 58%, and a 78% ORR was achieved with the addition of patients who had a clinical improvement.
In ASM, the ORR was 100%, and 1 of 2 patients achieved a complete remission with or without partial hematologic recovery.
And in a preplanned subgroup analysis, AYVAKIT demonstrated efficacy regardless of antineoplastic therapy.
In patients with prior antineoplastic therapy (including midostaurin), the ORR was 48.6%.
In treatment-naïve patients, the ORR was 72.2%.
Let’s now talk through AYVAKIT safety information.
AYVAKIT was evaluated in 148 patients in the EXPLORER and PATHFINDER trials. Patients received a starting dose of AYVAKIT ranging from 30 milligrams to 400 milligrams orally once daily and 131 patients were centrally confirmed to have Advanced SM, including 80 patients who received the recommended starting dose of 200 milligrams once daily.
AYVAKIT was generally well tolerated, and the majority of adverse reactions observed in patients treated with AYVAKIT were Grade 1 or Grade 2.
Fatal adverse reactions occurred in 2 out of 80 patients, or 2.5%, who received the recommended starting dose of 200 milligrams. No specific adverse reaction leading to death was reported in more than 1 patient.
10% of patients permanently discontinued due to any adverse reaction at the recommended starting dose of 200 milligrams.
Serious adverse reactions were seen in 34% of patients receiving the recommended starting dose of 200 milligrams.
The most common adverse reactions at all doses, occurring in at least 20% of patients, were edema, diarrhea, nausea, and fatigue or asthenia.
Cognitive adverse reactions can occur in patients receiving AYVAKIT. Depending on the severity, withhold AYVAKIT and then resume at the same dose or at a reduced dose upon improvement, or permanently discontinue.
Important Safety Information Voice-over:
Cognitive adverse reactions occurred in 39% of 749 patients and in 28% of 148 SM patients (3% were Grade >3).
Memory impairment occurred in 16% of patients; all events were Grade 1 or 2.
Cognitive disorder occurred in 10% of patients; less than 1% of these events were Grade 3.
Confusional state occurred in 6% of patients; less than 1% of these events were Grade 3.
Other events occurred in less than 2% of patients.
Dr Mesa Voice-over:
This table summarizes adverse reactions experienced by at least 10% of patients with Advanced SM receiving the 200 milligrams once daily starting dose of AYVAKIT.
Here we can see lab abnormalities experienced by at least 10% of patients receiving the 200 milligrams once daily starting dose of AYVAKIT in the EXPLORER and PATHFINDER trials.
AYVAKIT can cause fetal harm when administered to pregnant women.
Advise females and males of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 weeks after the final dose.
Please see the full Prescribing Information for additional safety information and details on dosing and administration.
For patients with Advanced SM, the recommended dosage of AYVAKIT is 200 milligrams orally, once daily.
AYVAKIT is also available in dose strengths of 100 milligrams, 50 milligrams, and 25 milligrams for dose modification for adverse reactions or drug interactions.
AYVAKIT should be taken orally, 1 time each day. Patients should take AYVAKIT on an empty stomach, at least 1 hour before or 2 hours after a meal.
Dose modifications are recommended for certain adverse reactions including, but not limited to, intracranial hemorrhage (or ICH), cognitive effects, and thrombocytopenia.
And it’s important to remember not to initiate AYVAKIT in patients with platelet counts less than 50,000 per microliter.
Be sure to make a monitoring plan with your patients and their caregivers when starting AYVAKIT treatment.
In clinical trials, it was common to to modify AYVAKIT dosage for adverse reactions.
Refer to AYVAKIT.com/HCP for more about recommended dosing instructions for AYVAKIT, including guidance for patient monitoring and dose modifications for adverse reactions.
Thanks so much for watching. Please take a moment to familiarize yourselves with the Important Safety Information associated with AYVAKIT.
Important Safety Information Voice-over:
AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with Advanced SM including patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia.
Limitations of Use: AYVAKIT is not recommended for the treatment of patients with Advanced SM with platelet counts of less than 50,000 per microliter.
IMPORTANT SAFETY INFORMATION
There are no contraindications for AYVAKIT.
Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in less than 1% of patients. Overall, ICH (for example, subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT. In Advanced SM patients who received AYVAKIT at 200 milligrams daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts greater than or equal to 50,000 per microliter prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts. Monitor patients closely for risk of ICH including those with thrombocytopenia, vascular aneurysm or a history of ICH or cerebrovascular accident within the prior year. Permanently discontinue AYVAKIT if ICH of any grade occurs. A platelet count must be performed prior to initiating therapy. AYVAKIT is not recommended in Advanced SM patients with platelet counts less than 50,000 per microliter. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks. After 8 weeks of treatment, monitor platelet counts every 2 weeks or as clinically indicated based on platelet counts. Manage platelet counts of less than 50,000 per microliter by treatment interruption or dose reduction.
Cognitive adverse reactions can occur in patients receiving AYVAKIT. Cognitive adverse reactions occurred in 39% of 749 patients and in 28% of 148 SM patients (3% were greater than Grade 3). Memory impairment occurred in 16% of patients; all events were Grade 1 or 2. Cognitive disorder occurred in 10% of patients; less than 1% of these events were Grade 3. Confusional state occurred in 6% of patients; less than 1% of these events were Grade 3. Other events occurred in less than 2% of patients. Depending on the severity, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.
AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks after the final dose.
The most common adverse reactions (greater than or equal to 20%) were edema, diarrhea, nausea, and fatigue or asthenia.
Avoid coadministration of AYVAKIT with strong and moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong and moderate CYP3A inducers.
To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see the full Prescribing Information for AYVAKIT at AYVAKIT.com/hcp.
Video Transcript
AYVAKIT Patient Management
Dr McCloskey Voice-over:
Hi, I’m Dr James McCloskey. Today we are going to talk about dosing and patient management with AYVAKIT.
AYVAKIT is indicated for the treatment of adult patients with Advanced Systemic Mastocytosis (or Advanced SM) including patients with aggressive systemic mastocytosis (or ASM), systemic mastocytosis with an associated hematological neoplasm (or SM-AHN), and mast cell leukemia (or MCL).
AYVAKIT is not recommended for the treatment of patients with Advanced SM with platelet counts of less than 50,000 per microliter.
For patients with Advanced SM, the recommended dosage of AYVAKIT is 200 milligrams orally, once daily.
Patients should take AYVAKIT on an empty stomach, at least 1 hour before or 2 hours after a meal.
AYVAKIT is also available in dose strengths of 100 milligrams, 50 milligrams, and 25 milligrams for dose modification for adverse reactions or drug interactions.
Dose modifications are recommended for certain adverse reactions including, but not limited to, intracranial hemorrhage (or ICH), cognitive effects, and thrombocytopenia.
And it’s important to remember not to initiate AYVAKIT in patients with platelet counts less than 50,000 per microliter.
Be sure to monitor patients at initiation and as indicated in the Prescribing Information during treatment to help reduce and manage potential adverse reactions.
Use with caution in patients with potential increased risk of ICH, including those with thrombocytopenia, vascular aneurysm, or a history of ICH or cerebrovascular accident within the prior year.
A platelet count should be performed prior to initiation of AYVAKIT, and then again every 2 weeks for the first 8 weeks of therapy, regardless of baseline platelet count.
After 8 weeks of therapy, the monitoring schedule depends on the platelet count.
If values are less than 75,000 per microliter, monitor platelet counts every 2 weeks or more frequently as clinically indicated.
If values are between 75,000 per microliter and 100,000 per microliter, monitor platelet counts every 4 weeks.
If values are greater than 100,000 per microliter, monitor platelet counts as clinically indicated.
Generally, in regards to your treatment plan, if a platelet count less than 50,000 per microliter occurs, interrupt AYVAKIT until the platelet count is greater than or equal to 50,000 per microliter—then resume at a reduced dose. We’ll go over the recommendations for dose reductions in a bit.
Finally, if platelet counts do not recover above 50,000 per microliter, consider platelet support.
You can find more information about platelet monitoring at AYVAKIT.com/hcp.
Looking at the trials, in EXPLORER and PATHFINDER, it was common to modify AYVAKIT dosage, and many of the patients had their dosage modified due to adverse reactions.
As we’ve discussed, thrombocytopenia can occur, but was generally reversible by reducing or interrupting treatment with AYVAKIT.
Dose interruptions and dose reductions for thrombocytopenia occurred in 20% and 22% of AYVAKIT- treated patients, respectively.
Among 80 Advanced SM patients in clinical trials who started at 200 milligrams per day, 60% had a dose interruption, 68% had a dose reduction with a median time to reduction of 6.9 weeks, and 10% permanently discontinued AYVAKIT.
Adverse reactions that required dosage interruption or dose reduction in more than 2% of patients who received AYVAKIT at 200 milligrams once daily included: thrombocytopenia, neutropenia, anemia, elevated blood alkaline phosphatase, cognitive disorder, peripheral edema, periorbital edema, fatigue, and arthralgia.
For recommended dose modifications: In patients experiencing ICH of any grade, AYVAKIT treatment should be permanently discontinued.
In patients with cognitive effects, recommended dose modification varies by grade. Depending on the severity, withhold AYVAKIT and then resume at the same dose or at a reduced dose upon improvement, or permanently discontinue.
In patients with thrombocytopenia who have platelet counts less than 50,000 per microliter, interrupt AYVAKIT until platelet count is greater than or equal to 50,000 per microliter. Then, resume at a reduced dose per the recommended reductions, which we’ll cover next. If platelet counts do not recover above 50,000 per microliter, consider platelet support.
For other adverse reactions of Grade 3 or Grade 4, withhold AYVAKIT until improvement to Grade 2 or less. Then, resume at the same dose or a reduced dose, as clinically appropriate.
The first recommended dose reduction is to 100 milligrams once daily, the second is to 50 milligrams once daily, and the third reduction is to 25 milligrams once daily.
Permanently discontinue AYVAKIT in patients with Advanced SM who are unable to tolerate a dose of 25 milligrams once daily.
As we’ve discussed, many patients in the EXPLORER and PATHFINDER trials had their doses modified due to adverse reactions. Patients in the studies were on treatment for a median of 1.7 months before a dose reduction.
Warnings and precautions for AYVAKIT include intracranial hemorrhage, cognitive effects, and embryo-fetal toxicity.
Serious ICH may occur with AYVAKIT treatment. Overall, ICH occurred in 2.9% of 749 patients who received AYVAKIT.
Fatal events occurred in less than 1% of patients.
Permanently discontinue AYVAKIT if ICH occurs.
Cognitive adverse reactions can occur in patients receiving AYVAKIT. Depending on the severity, withhold AYVAKIT and then resume at the same dose or at a reduced dose upon improvement, or permanently discontinue.
AYVAKIT can cause fetal harm when administered to pregnant women. Advise females and males of reproductive potential of the potential risk to a fetus and to use effective contraception during treatment and for 6 weeks after the final dose.
Please see the full Prescribing Information for additional safety information and details on dosing and administration.
Remember, you can find everything we covered here and more, including downloadable resources, at AYVAKIT.com/HCP.
Thanks so much for your time. Please take a moment to familiarize yourself with the Important Safety Information associated with AYVAKIT.
Important Safety Information Voice-over:
AYVAKIT® (avapritinib) is indicated for the treatment of adult patients with Advanced SM including patients with aggressive systemic mastocytosis, systemic mastocytosis with an associated hematological neoplasm, and mast cell leukemia.
Limitations of Use: AYVAKIT is not recommended for the treatment of patients with Advanced SM with platelet counts of less than 50,000 per microliter.
IMPORTANT SAFETY INFORMATION
There are no contraindications for AYVAKIT.
Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in less than 1% of patients. Overall, ICH (for example, subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT. In Advanced SM patients who received AYVAKIT at 200 milligrams daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts greater than or equal to 50,000 per microliter prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts. Monitor patients closely for risk of ICH including those with thrombocytopenia, vascular aneurysm or a history of ICH or cerebrovascular accident within the prior year. Permanently discontinue AYVAKIT if ICH of any grade occurs. A platelet count must be performed prior to initiating therapy.
AYVAKIT is not recommended in Advanced SM patients with platelet counts less than 50,000 per microliter. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks. After 8 weeks of treatment, monitor platelet counts every 2 weeks or as clinically indicated based on platelet counts. Manage platelet counts of less than 50,000 per microliter by treatment interruption or dose reduction.
Cognitive adverse reactions can occur in patients receiving AYVAKIT. Cognitive adverse reactions occurred in 39% of 749 patients and in 28% of 148 SM patients (3% were greater than Grade 3). Memory impairment occurred in 16% of patients; all events were Grade 1 or 2. Cognitive disorder occurred in 10% of patients; less than 1% of these events were Grade 3. Confusional state occurred in 6% of patients; less than 1% of these events were Grade 3. Other events occurred in less than 2% of patients. Depending on the severity, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.
AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks after the final dose.
The most common adverse reactions (greater than or equal to 20%) were edema, diarrhea, nausea, and fatigue/asthenia.
Avoid coadministration of AYVAKIT with strong and moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong and moderate CYP3A inducers.
To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please see the full Prescribing Information for AYVAKIT at AYVAKIT.com/HCP.
The downloadable materials below are here to provide additional support and information for you and your patients on AYVAKIT.
Dosing and Patient Management Guide for Advanced SM
Product Order Sheet for Advanced SM
Access and Reimbursement Guide
Product Brochure for Advanced SM
Identifying Advanced SM
Patient Brochure
for Advanced SM
These materials are intended for digital use only. If you decide to print them, please be sure to print and attach a copy of the full Prescribing Information as well.
Sign up to receive updates on AYVAKIT for Advanced SM and connect with a representative.
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ACCESS SUPPORT
IMPORTANT SAFETY INFORMATION
There are no contraindications for AYVAKIT.
Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. Overall, ICH (eg, subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT. In AdvSM patients who received AYVAKIT at 200 mg daily, ICH occurred in 2 of 75 patients (2.7%) who had platelet counts ≥50 x 109/L prior to initiation of therapy and in 3 of 80 patients (3.8%) regardless of platelet counts. Monitor patients closely for risk of ICH including those with thrombocytopenia, vascular aneurysm or a history of ICH or cerebrovascular accident within the prior year. Permanently discontinue AYVAKIT if ICH of any grade occurs. A platelet count must be performed prior to initiating therapy. AYVAKIT is not recommended in AdvSM patients with platelet counts <50 x 109/L. Following treatment initiation, platelet counts must be performed every 2 weeks for the first 8 weeks. After 8 weeks of treatment, monitor platelet counts every 2 weeks or as clinically indicated based on platelet counts. Manage platelet counts of <50 x 109/L by treatment interruption or dose reduction.
Cognitive adverse reactions can occur in patients receiving AYVAKIT. Cognitive adverse reactions occurred in 39% of 749 patients and in 28% of 148 SM patients (3% were Grade >3). Memory impairment occurred in 16% of patients; all events were Grade 1 or 2. Cognitive disorder occurred in 10% of patients; <1% of these events were Grade 3. Confusional state occurred in 6% of patients; <1% of these events were Grade 3. Other events occurred in < 2% of patients. Depending on the severity, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.
AYVAKIT can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. Advise females and males of reproductive potential to use an effective method of contraception during treatment with AYVAKIT and for 6 weeks after the final dose of AYVAKIT. Advise women not to breastfeed during treatment with AYVAKIT and for 2 weeks after the final dose.
The most common adverse reactions (≥20%) at all doses were edema, diarrhea, nausea and fatigue/asthenia.
Avoid coadministration of AYVAKIT with strong and moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong and moderate CYP3A inducers.
To report suspected adverse reactions, contact Blueprint Medicines Corporation at 1-888-258-7768 or the FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
Please click here to see the full Prescribing Information for AYVAKIT.
INDICATION
AYVAKIT is indicated for the treatment of adult patients with Advanced SM (AdvSM) including patients with aggressive systemic mastocytosis (ASM), systemic mastocytosis with an associated hematological neoplasm (SM-AHN), and mast cell leukemia (MCL).
Limitations of Use: AYVAKIT is not recommended for the treatment of patients with AdvSM with platelet counts of <50 x 109/L.
References:
- AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; June 2021.
- Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Systemic Mastocytosis V. 3.2021.© National Comprehensive Cancer Network, Inc. 2021. All rights reserved. Accessed July 12, 2021. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
- Gilreath JA, et al. Clin Pharmacol. 2019;11:77-92.
- Verstovsek S. Eur J Haematol. 2013;90(2):89-98.
- Garcia-Montero AC, et al. Blood. 2006;108(7):2366-2372.
- Data on file. Blueprint Medicines Corporation, Cambridge, MA. 2021.
- Gotlib J, et al. Blood.2013;121(13):2393-2401.
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