Interview with Lucia Masarova, Assistant Professor at MD Anderson Cancer Center

The clinical phase II study with tasquinimod in myelofibrosis has dosed its first patient. In this interview, the Principal Investigator Dr. Lucia Masarova speaks on the background and rationale for the clinical study.

– Could you tell us about your current work and what are your primary research interests?

– I am an Assistant Professor at the Leukemia Department in the MD Anderson Cancer Center, the largest cancer center dedicated to treat leukemias in the world. I trained under the world-leading experts and developed a passion for rare diseases called myeloproliferative neoplasms, on which I focus my clinical and research interest.

Owing to our large referral center, my clinic has the largest number of patients with this disease and, as lead or co-lead, I also participate in principal clinical trials designed for these patients. Clinical research is focused on deeper identification of disease subtypes, predictive factors and mechanisms of progression, molecular sequencing, correlation of disease molecular signatures with responses to therapies and long-term disease behavior.

Patients with myeloproliferative neoplasms have heterogeneous disease courses, from very indolent to very aggressive, and their individual lifespans vary from year to decades, and therefore, they have a vast array of clinical needs. They commonly experience various symptoms, often debilitating and affecting quality of life, frequently present with compromised bone marrow function, and they ultimately face progression to acute leukemia with dismal prognosis.

Beyond better understanding of the disease biology, my clinical research focuses on developing novel therapies to address complex issues of the disease; novel therapies that could prevent the disease from progression, therapies for both patients whose disease has progressed on currently approved medications and for those with a disease progressing towards the acute phase. In our department, we are constantly initiating, joining, or developing new therapies for our patients, and our primary therapy option often represents clinical trial.

– How are patients with myelofibrosis treated at your clinic?

– As mentioned, we are the largest academic center focused on leukemias and have one of the largest referral centers for myeloproliferative neoplasms patients. We offer clinical trials as an initial therapy to all potentially eligible patients. We have been the leading group for approval of all currently available therapies for patients with myelofibrosis, the most aggressive myeloproliferative neoplasms, but our research does not stop there.

After a drug approval, we initiate, propose, or explore existing agents in combinations, novel schedules or expanded patient’s population, and we are always looking for new molecules to explore in this rare disease. If patients are not eligible for a clinical trial, they are offered standard-of-care approved agents, which for symptomatic patients represent inhibitors of the JAK-STAT pathway, currently there are four FDA approved JAK – inhibitors: ruxolitinib, fedratinib, pacritinib and momelotinib. Patients with anemia or other needs are offered add-on agents as available.

– Where are the biggest medical needs in the treatment of myelofibrosis?

– With the approval of two recent JAK inhibitors, pacritinib and momelotinib, we have better options for those with low blood counts, so called cytopenic myelofibrosis, as both were approved for patients with thrombocytopenia and anemia, respectively. However, we have learned that JAK inhibitors ultimately fail, and patients then face poor outcomes with very limited choices and life-expectancy.

Advanced myelofibrosis is a challenging disease and minimal progress has been done if it progresses to accelerated phase or acute leukemia, e.g., increasing immature bone marrow cells called blasts. These patients have a terminal disease unless they can achieve disease control and undergo allogeneic stem cell transplantation, which is rare, as they are usually older and often have decreased performance due to disease debilitating symptoms. So it is of utmost importance to address the best therapies for specific disease needs and particularly develop agents for those patients with higher blasts.

– What are your expectations from the tasquinimod clinical trial in MF at your clinic?

– Based on the preliminary published evidence and data on the possible ability of tasquinimod to affect critical pathways involved in progression of myelofibrosis via S100A/B alterations, we hope to see changes in dependent disease features, such as cytopenias, additional effect on inflammation and possible stabilization of disease progression.

In our lab, we have explored tasquinimod in the advanced and blastic phase of myelofibrosis and saw very promising findings. This would represent a major clinical breakthrough for our patients who currently face advanced myelofibrosis. At first, we plan to explore the safety and efficacy of tasquinimod alone in patients who failed standard therapy and in parallel in combination with currently available JAK inhibitors, including those with moderately increased blasts, but hopefully this could follow broader exploration in more aggressive disease.