Enasidenib has demonstrated effectiveness in the treatment of a patient with relapsed/refractory aggressive systematic mastocytosis (SM) that harbors an IDH2 mutation, according to findings from a case report published recently in the journal Leukemia and Lymphoma.
The case report described a 75-year-old female who had been diagnosed with indolent SM 23 years ago. At that time, she had developed anemia, in which low hemoglobin levels were reported.
Around five years ago, the results of blood tests showed decreased absolute neutrophil counts and elevated tryptase levels. Findings from a bone marrow biopsy showed a hypercellular marrow, abnormal clonal mast cell population, aggregates of mast cells that stained positive for CD117, and atypical expression of CD25 with focal CD2.
What was the patient’s diagnosis?
A negative KIT D816V mutation test was reported. Because no evidence of an associated myeloid neoplasm was observed, the patient received a diagnosis of aggressive SM.
Read more about SM treatment and care
How was the patient treated?
Her initial treatment was imatinib 400 mg per day, which was discontinued 4 months later because of worsening anemia and no treatment response.
Next, midostaurin 150 mg every 12 hours was started. At one month after treatment initiation, the midostaurin dose was reduced to 75 mg every 12 hours because the patient was experiencing nausea, vomiting, and diarrhea.
Her midostaurin 75-mg-every-12-hours dose was maintained for 4 months, at which time the dose was increased to 100 mg twice daily because of elevated tryptase levels and worsening cytopenias.
Treatment course changed following bone marrow biopsy
The patient was referred to MD Anderson Cancer Center at the time that her increased tryptase concentrations and worsening cytopenias were observed.
A repeat bone marrow biopsy was performed 12 months following midostaurin initiation because of rising tryptase levels. Findings revealed a persistent abnormal mast cell population with a KIT D816V mutation identified using next-generation sequencing (NGS).
She continued midostaurin treatment for an additional 8 months, at which time new-onset splenomegaly was observed, along with continually increasing tryptase levels.
A new bone marrow biopsy obtained at this time showed a hypercellular marrow with a persistently elevated abnormal mast cell population and a KIT D816V mutation.
Based on NGS testing, the presence of IDH2, CBL and SRF2 mutations was revealed as well. Because of these findings, along with continuously elevated tryptase levels and hypercellularity of the bone marrow, the patient was switched to avapritinib 200 mg per day.
Enasidenib treatment shows positive results
After four months on avapritinib therapy, weight loss, progressive splenomegaly and sarcopenia (loss of muscle) were reported, together with persistently elevated tryptase levels.
At this time, her treatment was switched once again—to enasidenib 100 mg. Within two months, the patient’s hemoglobin levels normalized, her weight/appetite improved, and she was able to resume her previous level of activity.
Within three months of enasidenib initiation, a dramatic decrease in her tryptase levels was reported. Her alkaline phosphatase and albumin levels normalized as well. There was no evidence of transaminitis, differentiation syndrome, hyperbilirubinemia, or any acute toxicities.
No reports are currently available on the use of targeted treatments such as enasidenib in patients with aggressive SM. An unmet need exists regarding such treatments for patients with the disorder following disease progression on standard therapies.
The authors noted that after more than 30 years of follow-up, “our patient continues on enasidenib therapy with improvement in cytopenias and ascites[,] and no significant adverse events.” They concluded that although “additional studies are needed, enasidenib may offer a role in the evolving [aggressive] SM therapeutic landscape.”