Case 1
A 10-year-old boy had been diagnosed with an optic chiasm pilomyxoid
astrocytoma (WHO grade II, BRAF:KIAA1549 fusion-positive). Prior therapy
included subtotal resection (STR), carboplatin and vinblastine, focal
photon radiation to 54 Gy, and trametinib. After three months of
trametinib, he experienced progressive disease (PD) and started
lenalidomide in addition to trametinib. Adverse effects on this
combination were limited to grade 1 rash and paronychia. He achieved 15
months of stable disease (SD) on combination therapy before experiencing
PD, prompting discontinuation of this therapy.
Case 2 A 6-year-old boy had been diagnosed with an optic pathway pilomyxoid
astrocytoma (WHO grade II, BRAF:KIAA1549 fusion-positive). Prior therapy
included carboplatin and vinblastine, everolimus, and two courses of
trametinib.
At five years of age, six months into his second course of trametinib,
he experienced PD and subsequently started lenalidomide in addition to
trametinib. After three months of combination therapy, magnetic
resonance imaging (MRI) of the brain demonstrated a partial response.
Seven months into combination therapy, trametinib and lenalidomide were
held due to urgent ventriculoperitoneal shunt revision. Within 48 hours,
he experienced near-complete vision bilateral loss. MRI of the brain
demonstrated a left posterior watershed territory hypoxic-ischemic
injury (Figure 1), with stable appearance of the optic pathway mass.
Multidisciplinary stroke team evaluation did not deem the area of injury
plausibly attributable to direct surgical manipulation or
tumor-associated vascular compression. Echocardiogram was negative for
thrombus. He discontinued trametinib and lenalidomide and started
radiation therapy.
Case 3 A 11-year-old girl was diagnosed with an optic pathway pilomyxoid
astrocytoma (WHO grade II, BRAF:KIAA1549 fusion-positive). Prior therapy
included carboplatin and vincristine, vinblastine monotherapy,
carboplatin, vinblastine and cetuximab, and focal photon radiation to 54
Gy before starting trametinib. She received 15 months of trametinib with
continued gradual PD before starting on lenalidomide. After four months
of combination therapy, MRI of the brain demonstrated SD. However,
surveillance echocardiogram identified severe biventricular dysfunction
with a left ventricular ejection fraction (LVEF) of 18%, fractional
shortening of 9%, and two mural thrombi in the left ventricular apex
(Figure 2); the right ventricle was also moderately depressed.
Echocardiograms performed prior to lenalidomide initiation demonstrated
normal biventricular function. Trametinib and lenalidomide were
discontinued, and she started enoxaparin and losartan. Within two weeks,
the thrombi were no longer detectable by echocardiogram, and after two
months, LVEF had recovered to 53%.