Ruben A. Mesa, MD

Ruben A. Mesa, MD, director, UT Health San Antonio MD Anderson Cancer Center, discusses advancements made in the treatment of patients with myeloproliferative neoplasms (MPNs).

It is an exciting time in terms of therapeutic progress made in MPNs, says Mesa. First, there have been further updates on the important role of long-acting interferons in the treatment of patients with essential thrombocythemia or polycythemia vera. Long-acting interferons are having an impact on outcomes and are possibly superior to the use of hydroxyurea, in both the first- and second-line settings. Data presented at the 2019 ASH Annual Meeting with long-acting interferons showed both thrombosis-free survival as well as a potential molecular impact in this space, says Mesa.

In myelofibrosis, a very robust set of therapies are being developed, adds Mesa. For example, investigators are examining a group of JAK inhibitors that are expected to complement each other in terms of their activity. Additionally, novel combinations comprised of drugs with different mechanisms of action, such as BET, TGF-β, and LSD1 inhibition, are also under exploration. New drugs are also in development for use as single agents, says Mesa.

We’re seeing parallel advances in the treatment of patients with myelodysplastic syndromes with oral hypomethylating agents; these agents will certainly have a benefit for patients with advanced MPNs, as well, concludes Mesa.

Videos

Ruben A. Mesa, MD, discusses advancements made in the treatment of patients with myeloproliferative neoplasms.

Dr. Mesa on Treatment Advancements Made in MPNs

Ruben A. Mesa, MD, director, UT Health San Antonio MD Anderson Cancer Center, discusses new trials and agents in the pipeline in myelofibrosis.

A study presented at the 2019 ASH Annual Meeting utilized the BET inhibitor, CPI-0610, alone or in combination with ruxolitinib (Jakafi) in patients with myelofibrosis. The BET inhibitor improved splenic response, symptom burden, anemia, and some degree of fibrosis. This was a multi-arm study that will now be entering a phase III trial, where it might be used in the frontline setting in combination with ruxolitinib, says Mesa.

Another study utilized an LSD1 inhibitor. This is still in the early stages, but similarly to CPI-0610, it showed activity in splenic response, symptom burden, anemia, and fibrosis.

Finally, data on luspatercept (Reblozyl) in combination with ruxolitinib was reported on as well. Luspatercept was found to improve anemia, an unmet need for patients with myelofibrosis. The approval of luspatercept in patients with myelodysplastic syndrome will likely make this an important therapeutic consideration, concludes Mesa.

Ruben A. Mesa, MD, discusses new trials and agents in the pipeline in myelofibrosis.
 
 

Dr. Mesa on New Trials and Agents in the Myelofibrosis Pipeline

Ruben A. Mesa, MD, director, The Mays Cancer Center, the newly named center of UT Health San Antonio MD Anderson Cancer Center, discusses the approval of fedratinib (Inrebic) in myelofibrosis and other JAK inhibitors in the treatment pipeline.

 for use in adult patients with intermediate-2 or high-risk primary or secondary (post-polycythemia vera or post-essential thrombocythemia) myelofibrosis, is available in the frontline and second-line setting, explains Mesa. Whether fedratinib or ruxolitinib (Jakafi) will be used will depend on the comfort level of patients and physicians for each drug, according to Mesa.

Other JAK inhibitors in the pipeline include 2 mature drugs that are close to FDA approval: momelotinib and pacritinib, says Mesa. The phase III MOMENTUM trial is evaluating the efficacy of momelotinib, a JAK1, JAK2, and ACVR1 inhibitor, versus active comparator danazol (Danocrine) in patients with symptomatic and anemic myelofibrosis who previously received a JAK inhibitor. Momelotinib can improve spleen symptoms and anemia, says Mesa. If the trial turns out to be successful, the aggregated data observed with the agent might result in regulatory approval, Mesa postulates.

The JAK2 and FLT3 inhibitor pacritinib has also had successful phase III trials, such as the PERSIST-1 trial, says Mesa. The recently launched phase III PACIFICA trial is examining the agent versus physician’s choice in patients with primary myelofibrosis, post-polycythemia vera myelofibrosis, or post-essential thrombocytopenia myelofibrosis with severe thrombocytopenia. Pacritinib is the only JAK inhibitor that has been used in patients with a platelet count <50,000, concludes Mesa.

Ruben A. Mesa, MD, discusses the approval of fedratinib in myelofibrosis and other JAK inhibitors in the treatment pipeline.

Dr. Mesa on JAK Inhibitors in the Pipeline for Myelofibrosis

Ruben A. Mesa, MD, director, The Mays Cancer Center, the newly named center of UT Health San Antonio MD Anderson Cancer Center, discusses the efficacy of fedratinib (Inrebic) in patients with myelofibrosis who have low platelet counts.

Fedratinib is a JAK2 and FLT3 inhibitor that was approved in August 2019 for the treatment of adult patients with intermediate-2 or high-risk primary or secondary myelofibrosis. Efficacy data from the phase III JAKARTA trial and safety data from the phase II JAKARTA-2 trial served as the basis for the agent’s approval.

Prior to the approval of fedratinib, ruxolitinib (Jakafi) was approved for use at a reduced dose in patients with a platelet count between 50,000 and 100,000. At the 2019 ASH Annual Meeting, investigators looked at the outcomes of patients with a platelet count between 50,000 and 100,000 who received 400 mg of fedratinib.

Results from the pooled analysis of the JAKARTA trials demonstrated that patients with a platelet count between 50,000 and 100,000 and ≥100,000 had a similar symptom resolution rate and spleen response rate, says Mesa. Moreover, 400 mg of daily fedratinib was found to be safe in patients with a platelet count between 50,000 and 100,000. However, several patients developed grade 3/4 thrombocytopenia and required dose modifications, concludes Mesa.

Author | Ruben A. Mesa, MD

Articles

Dr. Mesa on Treatment Advancements Made in MPNs

Dr. Mesa on New Trials and Agents in the Myelofibrosis Pipeline

Dr. Mesa on JAK Inhibitors in the Pipeline for Myelofibrosis

Dr. Mesa on the Efficacy of Fedratinib in Patients With Myelofibrosis and Low Platelet Counts