LCL161 in Treating Patients With Myelofibrosis: Phase II Trial Results

By Patrick Daly - Last Updated: November 10, 2021

A trial examined weekly administration of LCL161 therapy in a large, high-risk, older study population with myelofibrosis (MF), and found that it appears to be a safe and effective treatment option. The phase II trial was led by Naveen Pemmaraju, MD, and colleagues. Their findings were published in Blood Advances.

Noting that JAK inhibitors are largely contraindicated in some patients, such as those with severe thrombocytopenia, the authors suggested that “there is an unmet medical need for the development of novel agents for patients with MF.”

The study comprised of a single-center trial with LCL161 (oral, starting dose, 1500 mg per week) administered to patients with intermediate- to high-risk MF. In the analysis, 66% of subjects had two or more prior therapies, and a median baseline platelet count of 52 × 103/?L, with 28% having ASXL1 mutations. Observers noted a 30% objective response. Notably, six patients achieved clinical improvement of anemia, four achieved hemoglobin response, and two achieved transfusion independence. The median overall survival (OS) was 34 months (range: 2.2 – 60.1+), and cIAP protein reductions were observed in all responders.

The most common toxicities reported in patients were: nausea/vomiting (64%, mainly grade I or II), fatigue (46%), and dizziness/vertigo (30%). There were four grade III or IV adverse events (two, syncope; one, nausea/vomiting; one, skin eruption/pruritis) observed in the study.

Researchers concluded that LCL161 exhibited safe and effective outcomes. Moreover, given the need for treatments beyond JAK inhibitors, the authors suggested that SMAC mimetics, like LCL161, may be a viable option for certain patients.