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Indolent ISMAdvanced SMPDGFRA GIST

SELECT A CONDITION

ISM

Indolent systemic mastocytosis (ISM)

AdvSM

Advanced systemic mastocytosis (AdvSM)

PDGFRA
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Gastrointestinal stromal tumors with PDGFRA mutation (PDGFRA GIST)

AYVAKIT® (avapritinib) 25 mg white logo

Hypothetical patient profiles for Advanced SM

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Evaluating AYVAKIT in patients with systemic mastocytosis with an associated hematological neoplasm (SM-AHN)

WHO Criteria9,10*
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The following hypothetical profiles are examples of patient types who may have a diagnosis of SM-AHN and are fictionalized through review of the published literature, clinical guidelines, clinical studies, and Prescribing Information for avapritinib. The information presented here does not represent medical advice for any individual patient; Blueprint Medicines does not directly or indirectly practice medicine.

Review of this material does not substitute for review of the AYVAKIT Prescribing Information, diagnostic criteria, clinical practice guidelines, and other reference literature about the diagnosis of Advanced SM. Healthcare providers should make all treatment decisions based on the individual patient circumstances and their clinical judgment.

It is the healthcare provider's discretion to assess which disease component (ie, SM or AHN) warrants immediate treatment.10
Olga Icon
OLGA
59-year-old
 female
James Icon
JAMES
64-year-old
 male
Mario Icon
MARIO
72-year-old
 male
Hypothetical patients. Individual results may vary.
icon olga
BaselineAyvakit Treatment
Meet Olga
59-year-old female with suspected SM-AHN (MPN-ET)1
Hypothetical patient. Individual results may vary.
PATIENT HISTORY AND PRESENTATION
  • MPN-ET diagnosis previously confirmed per WHO diagnostic criteria
  • Olga returned to her doctor reporting pain throughout the body, discomfort in the abdominal area, unexpected weight loss, and chest pain along with dry cough11
  • Ongoing symptoms prompted Olga to request time off from work and cancel a vacation in order to work with her healthcare team to find the source of her health issues
CLINICAL WORKUP
  • Clinical workup showed elevated serum tryptase, low hemoglobin, and normal platelet count12,13
    • Due to elevated serum tryptase along with gastrointestinal symptoms, a full myeloid mutation profile was requested, including KIT D816V8,11
    • Myleoid mutation profile detected JAK2 but not KIT D816V, so a high-sensitivity KIT D816V test was conducted, which confirmed a KIT D816V mutation
  • Physical examination and imaging confirmed marked splenomegaly, pleural effusion requiring use of diuretics, and osteoporosis associated with bone pain8
KIT=KIT proto-oncogene, receptor tyrosine kinase; SM-AHN (MPN-ET)=systemic mastocytosis with an associated clonal hematological myeloproliferative neoplasm-essential thrombocythemia; WHO=World Health Organization.
Findings at Baseline8,12-17
Serum tryptase176 ng/mL
Hemoglobin8.2 g/dL
Platelet count450 x 109/L
Myeloid mutation profileDetection of JAK2
KIT status and methodKIT D816V+ confirmed by high-sensitivity (<1% limit of detection) ddPCR in peripheral blood
Bone marrow biopsy
  • 16 mast cell aggregates with spindled forms (60%)
  • Mast cells in bone marrow express CD25
Physical examination/imaging
  • Splenomegaly
  • Pleural effusion
  • Osteoporosis
Olga was diagnosed with SM-AHN and was prescribed AYVAKIT for Advanced SM.

Please see WHO criteria for more information about diagnosis.9
Results With AYVAKIT Treatment1,18
AYVAKIT efficacy results in the clinical studies were based on an ORR under the modified IWG response criteria for Advanced Systemic Mastocytosis. These studies were not powered to demonstrate a response on each of the individual AHN components or data points included above. This information is hypothetical and individual results may vary.
  • Olga was started on AYVAKIT 200 mg once daily. Per dosing guidelines, platelets were monitored every 2 weeks for the first 8 weeks1
  • As treatment continued, Olga told her care team that she noted her bone pain subsided and her lower abdominal pain was reduced
  • Olga experienced headaches and dizziness after 3 months of treatment1
  • Olga continued on 200 mg of AYVAKIT once daily1
Clinical Findings After 12 Weeks1,18
Treatment1,18AYVAKIT 200 mg once daily
Serum tryptase1879.2 ng/mL
Hemoglobin1812.4 g/dL
Platelet count1,18180 x 109/L
Continued treatment18
  • 60% reduction in neoplastic mast cells in bone marrow biopsy
  • 30% reduction in splenomegaly volume
Adverse events experienced during AYVAKIT treatment and dose modifications1,18
  • Grade 1 neutrophil count decrease and Grade 1 decrease in lymphocytes
  • Grade 1 headaches
  • Grade 1 dizziness
  • No dose modifications were made
Duration of treatment1,18Remains on treatment for >1 year at 200 mg
AHN=associated hematological neoplasm; IWG=International Working Group; ORR=overall response rate.
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icon james
BaselineAyvakit Treatment
Meet James
64-year-old male diagnosed with SM-AHN (CMML-0)1
Hypothetical patient. Individual results may vary.
PATIENT HISTORY AND PRESENTATION
  • CMML-0 diagnosis previously confirmed per WHO diagnostic criteria
  • James was under periodic observation to monitor disease progression and emergence of clinically significant symptoms19
  • James returned to his doctor, presenting with fatigue, hypersensitivity to pollen, and long-standing maculopapular skin rashes that resulted in pruritus11
  • Symptoms did not improve, and James was now experiencing weight loss in addition to continuing fatigue11
  • James reported that his fatigue limits the time he can spend with his grandchildren
CLINICAL WORKUP
  • Clinical workup showed enlarged spleen, abnormal levels of serum tryptase, low hemoglobin, and low platelet count. In addition, high-sensitivity PCR assay in peripheral blood confirmed KIT D816V8,12,17
  • Bone marrow biopsy confirmed the presence of spindle-shaped neoplastic mast cell aggregates10
KIT=KIT proto-oncogene, receptor tyrosine kinase; PCR=polymerase chain reaction; SM-AHN (CMML-0)=systemic mastocytosis with associated clonal hematological chronic myelomonocytic leukemia–subtype 0; WHO=World Health Organization.
Findings at Baseline8,12,14,16,17,20
Serum tryptase209 ng/mL
Hemoglobin10.2 g/dL
Platelet count 135 x 109/L
Peripheral blood blast count1% peripheral blasts
Absolute monocyte count10% persistent >3 months
Myeloid mutation profileDetection of KIT D816V, SRSF2, TET2
KIT status and methodKIT D816V+ confirmed by high-sensitivity (<1% limit of detection) ddPCR in peripheral blood
Bone marrow biopsy
  • Mast cells in the bone marrow express CD25
  • Mast cells in aggregates of ≥15 mast cells/cluster; 30%-35% of mast cells appearing spindle-shaped; bone marrow blast at 4%
Physical examination/imaging
  • Palpable splenomegaly >5 cm examination/imaging hypersplenism
  • Hepatomegaly with mild ascites
James was diagnosed with SM-AHN and was prescribed AYVAKIT for Advanced SM.

Please see WHO criteria for more information about diagnosis.9
Results With AYVAKIT Treatment1,18
AYVAKIT efficacy results in the clinical studies were based on an ORR under the modified IWG response criteria for Advanced Systemic Mastocytosis. These studies were not powered to demonstrate a response on each of the individual AHN components or data points included above. This information is hypothetical and individual results may vary.
  • James was started on AYVAKIT 200 mg once daily. Per dosing guidelines, platelets were monitored every 2 weeks for the first 8 weeks1
  • James returned with facial edema, and reported feeling confused and lost1
    • Per AYVAKIT dosing guidelines, dose was interrupted for 8 weeks and treatment was resumed at 100 mg
  • After 1 year of treatment, James continued to be maintained on therapy at 100 mg daily and was tolerating it well
Clinical Findings After 12 Weeks1,18
Treatment1,18AYVAKIT 200 mg once daily
Serum tryptase1883.6 ng/mL
Platelet count1,18185 x 109/L
Continued treatment18
  • Bone marrow biopsy showed 60% reduction in neoplastic mast cell aggregates
  • No palpation of spleen ≥5 cm below the ribs, radiological examination showed a decrease in spleen and liver volume
Adverse events experienced during AYVAKIT treatment and dose modifications1,18
  • Grade 1 facial edema
  • Grade 2 cognitive effect (confusion and feeling lost)
  • Dose reduced to 100 mg once daily
Duration of treatment1,18Remains on treatment for >1 year at 100 mg
AHN=associated hematological neoplasm; IWG=International Working Group; ORR=overall response rate.
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icon mario
BaselineAyvakit Treatment
Meet Mario
72-year-old male with suspected SM-AHN (very low-risk MDS)1,21
Hypothetical patient. Individual results may vary.
PATIENT HISTORY AND PRESENTATION
  • Mario visited his doctor with complaints of extreme tiredness that caused significant impact on his daily activities11
  • Mario is experiencing weight loss and reports that extended periods of diarrhea prevent him from spending time outside of his home11
CLINICAL WORKUP
  • Clinical workup detected enlarged spleen, low hemoglobin, and low platelet count8,12
  • Due to abnormal CBC, a myeloid mutation test was requested8
  • Bone marrow biopsy showed spindle-shaped mast cell aggregates10
CBC=complete blood count; ICH=intracranial hemorrhage; KIT=KIT proto-oncogene, receptor tyrosine kinase; SM-AHN (very low-risk MDS)=systemic mastocytosis with associated clonal–very low-risk hematological myelodysplastic syndrome; WHO=World Health Organization.
Findings at Baseline7,8,12,14,17,22
Serum
 tryptase		256 ng/mL
Hemoglobin8.8 g/dL
Platelet
 count		75 x 109/L
Absolute
 neutrophil
 count		1.4 x 109/L
Myeloid mutation profileDetection
 of SF3B1
KIT status
 and method		KIT D816V+ confirmed by high-sensitivity (<1% limit of detection) ddPCR in peripheral blood
Bone marrow
 biopsy
  • ≥50% of mast cells are spindle-shaped in mast cell infiltrates
  • CD117 and CD25 detected in mast cells
Physical examination/
imaging		Palpable splenomegaly with hypersplenism
Other
 remarkable
 findings
  • Hypoalbuminemia with albumin at 2 g/dL
  • Thrombocytopenia
Mario was diagnosed with SM-AHN and was prescribed AYVAKIT for Advanced SM.
Please see WHO criteria for more information about diagnosis.9
Results With AYVAKIT Treatment1,18
AYVAKIT efficacy results in the clinical studies were based on an ORR under the modified IWG response criteria for Advanced Systemic Mastocytosis. These studies were not powered to demonstrate a response on each of the individual AHN components or data points included above. This information is hypothetical and individual results may vary.
  • Mario was started on AYVAKIT 200 mg once daily. Per dosing guidelines, platelets were monitored every 2 weeks for the first 8 weeks1
  • Mario started to experience grade 1 periorbital edema and grade 1 fatigue, diarrhea, and nausea
    • Platelet counts reduced to 48 x 109/L
      • Dose was interrupted for 8 weeks until platelet count >50 x 109/L
      • Treatment resumed at 100 mg once daily with continued platelet monitoring
  • After 1 year of treatment, Mario continued to be maintained on therapy at 100 mg daily and continues to be monitored for adverse reactions
Clinical Findings After 12 Weeks1,18
Treatment1,18AYVAKIT 200 mg once daily
Serum tryptase1818 ng/mL
Hemoglobin189.3 g/dL
Platelet count1,1890 x 109/L
Absolute neutrophil count182.0 x 109/L
Bone marrow biopsy18No presence of mast cell infiltrates in the bone marrow
Physical examination and other remarkable findings1,18
  • No palpation of splenomegaly
  • Albumin at 3.8 g/dL
Adverse events experienced during AYVAKIT treatment and dose modifications1,18
  • Grade 2 diarrhea
  • Grade 1 neutropenia
  • Dose reduced to 100 mg once daily
Duration of treatment1,18Remains on treatment for >1 year at 100 mg
AHN=associated hematological neoplasm; IWG=International Working Group; ORR=overall response rate.
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INDICATION

AYVAKIT® (avapritinib) 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.

IMPORTANT SAFETY INFORMATION
INDICATION & IMPORTANT SAFETY INFORMATION

Intracranial Hemorrhage—Serious intracranial hemorrhage (ICH) may occur with AYVAKIT treatment; fatal events occurred in <1% of patients. Overall, ICH (e.g., subdural hematoma, ICH, and cerebral hemorrhage) occurred in 2.9% of 749 patients who received AYVAKIT in clinical trials. 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 factors of ICH which may include history of vascular aneurysm, ICH or cerebrovascular accident within the prior year, concomitant use of anticoagulant drugs, or thrombocytopenia. Symptoms of ICH may include headache, nausea, vomiting, vision changes, or altered mental status. Advise patients to seek immediate medical attention for signs or symptoms of ICH. 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 Effects—Cognitive adverse reactions can occur in patients receiving AYVAKIT and occurred in 33% of 995 patients overall in patients who received AYVAKIT in clinical trials including 28% of 148 AdvSM patients (3% were Grade ≥3). Depending on the severity and indication, withhold AYVAKIT and then resume at same dose or at a reduced dose upon improvement, or permanently discontinue.

Photosensitivity—AYVAKIT may cause photosensitivity reactions. In all patients treated with AYVAKIT in clinical trials (n=1049), photosensitivity reactions occurred in 2.5% of patients. Advise patients to limit direct ultraviolet exposure during treatment with AYVAKIT and for one week after discontinuation of treatment.

Embryo-Fetal Toxicity—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 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 following the final dose.

Adverse Reactions—The most common adverse reactions (≥20%) were edema, diarrhea, nausea, and fatigue/asthenia.

Drug Interactions—Avoid coadministration of AYVAKIT with strong or moderate CYP3A inhibitors. If coadministration with a moderate CYP3A inhibitor cannot be avoided, reduce dose of AYVAKIT. Avoid coadministration of AYVAKIT with strong or 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.

References:

  1. AYVAKIT [prescribing information]. Cambridge, MA: Blueprint Medicines Corporation; May 2023.
  2. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Systemic Mastocytosis V.4.2023. © National Comprehensive Cancer Network, Inc. 2023. All rights reserved. Accessed November 20, 2023. 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.
  3. Gilreath JA et al. Clin Pharmacol. 2019;11:77-92.
  4. Verstovsek S. Eur J Haematol. 2013;90(2):89-98.
  5. Garcia-Montero AC et al. Blood. 2006;108(7):‍2366-2372.
  6. Kristensen T et al. Am J Hematol. 2014;89(5):493-498.
  7. Data on file. Blueprint Medicines Corporation, Cambridge, MA. 2021.
  8. Gotlib J et al. Blood. 2013;121(13):‍2393-2401.
  9. WHO Classification of Tumours Editorial Board. Haematolymphoid tumours. [Internet; beta version ahead of print]. Lyon (France): International Agency for Research on Cancer; 2022 [cited September 20, 2023]. (WHO Classification of Tumours Series. 5th ed.; vol. 11). Available from: https://tumourclassification.iarc.who.int/chapters/63
  10. Pardanani A. Am J Hematol. 2023;98(7):1097-1116.
  11. Theoharides TC et al. N Engl J Med. 2015;373(2):163-172.
  12. Pardanani A et al. Blood. 2009;114(18):‍3769-3772.
  13. Passamonti F, Maffioli M. Hematology Am Soc Hematol Educ Program. 2016;2016(1):534-542.
  14. Valent P et al. Blood. 2017;129(11):1420-1427.
  15. Stoecker MM, Wang E. Arch Pathol Lab Med. 2012;136(7):832-838.
  16. Arber DA et al. Blood. 2016;127(20):‍2391-2405.
  17. Greiner G et al. Clin Chem. 2018;64(3):547-555.
  18. Gotlib J et al. Nat Med. 2021;27(12):‍2192-2199.
  19. Kwon J. Blood Res. 2021;56(suppl 1):S5-S16.
  20. Meggendorfer M et al. Blood. 2012;120(15):‍3080-3088.
  21. Greenberg PL et al. Blood. 2012;120(12):‍2454-2465.
  22. Malcovati L et al. Blood. 2020;136(2):157-170.