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Innovative Medicines & Omics Subdural hematoma associated with avapritinib

for GISTs include surgery, radiation therapy, and targeted 2. Case presentation
drug therapy with imatinib and sunitinib. Surgery might
be performed to remove the primary tumor and any A 66-year-old man with a history of GIST presented (in
associated regional lymph nodes. Chemotherapy and early May 2024) to the emergency room along with his
wife with complaints of worsening altered mental status,
targeted therapy aim to slow tumor growth and shrink confusion, gait changes, and global weakness. They denied
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the tumor by applying drugs targeting cancerous cells. any occurrence of recent trauma or falls. However, the
However, some patients are resistant to these treatments, patient has had multiple “near falls.” In early 2019, he was
whereas others experience severe side effects. This has led diagnosed with a small bowel GIST with metastases to the
to the exploration of new treatment options, including a liver – grade 1, pT3 pNX pM1 (liver), stage IV. Imatinib was
highly selective inhibitor of mutated forms of two proteins- initiated at diagnosis in February 2019. Disease progression
receptor tyrosine kinase type III (KIT) and platelet-derived was monitored closely. In December 2020, next-generation
growth factor receptor-alpha (PDGFRA) commonly found sequencing revealed two KIT mutations, one in exon 17
in GISTs. 3 and the other in exon 9, and <1% programmed death ligand
A recent clinical trial showed promising results for 1 mutations. In February 2021, regorafenib was initiated
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avapritinib in treating GISTs (Figure 1). Avapritinib as a second-line treatment. Unfortunately, the disease
demonstrated a high response rate and prolonged progressed further, and various therapies were used. Sutent
progression-free survival in a phase 1 trial involving patients was initiated in April 2021, ripretinib in January 2022, Y90
with advanced GIST who had undergone unsuccessful therapy to a part of the liver in July 2022, Cabometyx in
treatments. The drug revealed a good safety profile with November 2022, and Avapritinib at the end of January
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manageable side effects. These findings have translated into 2024. While being treated with avapritinib (300 mg), the
the FDA approval of avapritinib to treat GISTs, presenting patient presented with periorbital edema (known side
new hope for patients with minimal treatment options. The effect of Avapritinib) and some new papules on his bilateral
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overall prognosis for patients with metastatic small bowel lower extremities, particularly along the feet. Thus, in April
GISTs is generally poor, with a 5-year survival rate of 15% 2024, the avapritinib dose was reduced to 200 mg.
– 20%. The emergence of various treatment modalities has The wife reported that the patient had worsening
thus far improved outcomes in selected subsets of patients altered mental status in the past few days and believed
and includes novel targeted therapies, immunotherapies, that it was caused by his medication, which the patient
and combination therapies. Ongoing studies into new had weaned and subsequently stopped earlier this week.
treatment strategies and methods for early detection are His mental status has still not improved, and he has had
being pursued to improve the survival and quality of life of an unsteady gait. At present, although he is fully oriented,
patients with metastatic small bowel GISTs. A significant his wife reported episodes of the patient getting dressed at
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safety concern associated with avapritinib is the risk home and not knowing where he was going. The patient
of intracranial hemorrhage (ICH), including subdural believed that the reason for the visit was abdominal pain
hematomas (SDH). Although these events are uncommon (right upper quadrant). He had a fever and vomiting (non-
in clinical trials, they affect approximately 2.4% of patients bloody and non-bilious). The patient denied the presence
receiving a starting dose of 300 mg. Patients with severe of skin infections, acute changes in hearing or vision,
thrombocytopenia (platelet counts <50 × 10 /L) at baseline unilateral weakness or paresthesia or vision loss, chest
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are at an increased risk of complications linked to mast pain, shortness of breath, cough, falls, seizures, drug or
cell infiltration in the bone marrow. This association was alcohol use, dysuria, and changes in urinary frequency.
observed during clinical trials of avapritinib in individuals The patient reported imbalance and confusion.
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with advanced systemic mastocytosis. All cases of Differential diagnosis included medication side effects;
intracranial bleeding (ICB) were directly attributed to however, even after stopping the drug, his symptoms
the treatment; however, the risk is significant enough to persisted. He did not exhibit focal symptoms; however,
warrant caution, particularly in patients predisposed to given his history, the plan was to obtain a computed
bleeding because of thrombocytopenia, anticoagulant use, tomography (CT) of the head to detect ICH or mass.
or previous vascular events. Thus, close monitoring of The laboratory results were inconsistent with toxic
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the platelet count is essential before and during treatment. metabolic etiologies such as electrolyte disturbances,
ICH symptoms, such as headache, nausea, vision changes, hypoglycemia, uremia, acidosis states, and infection
or altered mental status, require immediate medical (i.e., sepsis). History examinations were performed, and
attention. Dose adjustments or treatment discontinuation toxidromes of intoxication or withdrawal, hypoxemia
may be necessary in patients with severe adverse effects. 10 or hypercarbia, liver disease or liver failure causing

Volume 2 Issue 1 (2025) 94 doi: 10.36922/imo.7068