Hypothetical
patient profiles
for Advanced SM

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

The World Health Organization (WHO) Diagnostic Criteria

Diagnosis of SM requires the presence of 1 major criterion and ≥1 minor criterion, or ≥3 minor criteria

Major criterion

  • Multifocal aggregates of ≥15 mast cells in bone marrow sections and/or other extracutaneous organ(s)

Minor criteria

  • In biopsy sections of bone marrow or other extracutaneous organs, >25% of mast cells in the infiltrate are spindle-shaped or have atypical morphology; or >25% of all mast cells in bone marrow aspirate smears are immature or atypical
  • Detection of an activating point mutation at codon 816 in KIT in bone marrow, blood, or another extracutaneous organ
  • Mast cells in bone marrow, blood, or other extracutaneous organs express CD2 and/or CD25, in addition to normal mast cell markers
  • Baseline serum total tryptase levels persistently >20 ng/mL (if the patient has an associated myeloid neoplasm, then this parameter is not valid)

For an Advanced SM diagnosis, criteria for one of the Advanced SM subtypes must be met

AGGRESSIVE SM (ASM)

  • ≥1 “C” findings and no evidence of mast cell leukemia
  • C-findings:
    • Bone marrow dysfunction manifested by ≥1 cytopenia(s) (absolute neutrophil count <1.0 x 109/L, hemoglobin <10 g/dL, or platelets <100 x 109/L)
    • Palpable hepatomegaly with impairment of liver function, ascites, and/or portal hypertension
    • Palpable splenomegaly with hypersplenism
    • Malabsorption with weight loss from gastrointestinal tract mast cell infiltrates
    • Skeletal involvement with large osteolytic lesions and/or pathologic fractures

SYSTEMIC MASTOCYTOSIS WITH AN ASSOCIATED HEMATOLOGIC NEOPLASM (SM-AHN)

  • Meets criteria for AHN as a distinct entity per the WHO classification

MAST CELL LEUKEMIA (MCL)

  • Bone marrow aspirate smears show ≥20% mast cells. In classic cases, mast cells account for ≥10% of peripheral blood white cells

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.9

  • OLGA
    59-year-old female

  • JAMES
    64-year-old male

  • MARIO
    72-year-old male

Hypothetical patients. Individual results may vary.
  • 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 cough10
    • 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 count11,12
      • Due to elevated serum tryptase along with gastrointestinal symptoms, a full myeloid mutation profile was requested, including KIT D816V7,10
      • 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 pain7

    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 Baseline7,8,11-15

    Serum tryptase 176 ng/mL
    Hemoglobin 8.2 g/dL
    Platelet count 450 x 109/L
    Myeloid mutation profile Detection of JAK2
    KIT status and method KIT 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.7,8

    Results With AYVAKIT Treatment1,16

    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 Weeks1,16

    Treatment1,16 AYVAKIT 200 mg once daily
    Serum tryptase16 79.2 ng/mL
    Hemoglobin16 12.4 g/dL
    Platelet count1,16 180 x 109/L
    Physical examination and other remarkable findings16
    • 60% reduction in neoplastic mast cells in bone marrow biopsy
    • 30% reduction in splenomegaly volume
    Adverse events experienced during AYVAKIT treatment and dose modifications1,16
    • Grade 1 neutrophil count decrease and Grade 1 decrease in lymphocytes
    • Grade 1 headaches
    • Grade 1 dizziness
    • No dose modifications were made
    Duration of treatment1,16 Remains on treatment for >1 year at 200 mg

    AHN=associated hematological neoplasm; IWG=International Working Group; ORR=overall response rate.

  • 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 symptoms17
    • James returned to his doctor, presenting with fatigue, hypersensitivity to pollen, and long-standing maculopapular skin rashes that resulted in pruritus10
    • Symptoms did not improve, and James was now experiencing weight loss in addition to continuing fatigue10
    • 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 D816V7,11,15
    • Bone marrow biopsy confirmed the presence of spindle-shaped neoplastic mast cell aggregates8

    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 Baseline7,8,11,14,15,18

    Serum tryptase 209 ng/mL
    Hemoglobin 10.2 g/dL
    Platelet count 135 x 109/L
    Peripheral blood blast count 1% peripheral blasts
    Absolute monocyte count 10% persistent >3 months
    Myeloid mutation profile Detection of KIT D816V,
    SRSF2, TET2
    KIT status and method KIT 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 below left costal margin with 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.7,8

    Results With AYVAKIT Treatment1,16

    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 Weeks1,16

    Treatment1,16 AYVAKIT 200 mg once daily
    Serum tryptase16 83.6 ng/mL
    Platelet count1,16 185 x 109/L
    Physical examination and other remarkable findings16
    • 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 modifications1,16
    • Grade 1 facial edema
    • Grade 2 cognitive effect (confusion and feeling lost)
    • Dose reduced to 100 mg once daily
    Duration of treatment1,16 Remains on treatment for >1 year at 100 mg

    AHN=associated hematological neoplasm; IWG=International Working Group; ORR=overall response rate.

  • Meet Mario
    72-year-old male with suspected SM-AHN
    (very low-risk MDS)1,19 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 activities10
    • Mario is experiencing weight loss and reports that extended periods of diarrhea prevent him from spending time outside of his home10

    CLINICAL WORKUP

    • Clinical workup detected enlarged spleen, low hemoglobin, and low platelet count7,11
    • Due to abnormal CBC, a myeloid mutation test was requested7
    • Bone marrow biopsy showed spindle-shaped mast cell aggregates8

    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 Baseline6-8,11,15,20

    Serum tryptase 256 ng/mL
    Hemoglobin 8.8 g/dL
    Platelet count 75 x 109/L
    Absolute neutrophil count 1.4 x 109/L
    Myeloid mutation profile Detection 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.7,8

    Results With AYVAKIT Treatment1,16

    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 Weeks1,16

    Treatment1,16 AYVAKIT 200 mg once daily
    Serum tryptase16 18 ng/mL
    Hemoglobin16 9.3 g/dL
    Platelet count1,16 90 x 109/L
    Absolute neutrophil count16 2.0 x 109/L
    Bone marrow biopsy16 No presence of mast cell infiltrates in the bone marrow
    Physical examination and other remarkable findings1,16
    • No palpation of splenomegaly
    • Albumin at 3.8 g/dL
    Adverse events experienced during AYVAKIT treatment and dose modifications1,16
    • Grade 2 diarrhea
    • Grade 1 neutropenia
    • Dose reduced to 100 mg once daily
    Duration of treatment1,16

    Remains on treatment for >1 year at 100 mg

    AHN=associated hematological neoplasm; IWG=International Working Group; ORR=overall response rate.

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