The intersection of research and practice

Advancing drug development for chronic leukemias

Investigators at the Mays Cancer Center at UT Health San Antonio play an essential role in the development of numerous cancer-related therapies. Among those successes are recent Food and Drug Administration approvals of new medications for chronic leukemias.

Decreasing blood-clot risk for polycythemia vera patients

With FDA approval in November 2021 of a new medication — RoPEG INFa2b (besremi) — for patients with the controllable, but chronic, form of blood cancer polycythemia vera (PV), the outlook has brightened.

“Besremi is the first therapy approved for the initial treatment of polycythemia vera where medical treatment is indicated,” said Ruben Mesa, MD, FACP. “Namely, it is for those PV patients in whom phlebotomy and aspirin are insufficient due to the risk of blood clots or significant symptoms of PV.”

For those patients, besremi helps safely control blood counts in a durable fashion, decrease risk of blood clots and improve disease-associated symptoms.

The problem occurs when PV patients make too many red blood cells in the bone marrow, which can increase the risk of clotting. White blood cells and platelets may also be elevated in some individuals. One treatment is phlebotomy, which, like a blood donation, removes some of the blood cells and thins the blood. Another treatment is low-dose aspirin.

Medication treatments to reduce the number of blood cells include hydroxyurea, interferon alfa drugs (including besremi), ruxolitinib, busulfan and chlorambucil. The approval of RoPEG INFa2b is a big step forward for the treatment of polycythemia vera, Mesa said.

The Mays Cancer Center currently co-leads the Global Surpass ET Trial for use of besremi in essential thrombocythemia, another myeloproliferative neoplasm.

New therapy for thrombocytopenia

Myelofibrosis (MF) is a rare but fatal bone marrow cancer. The Mays Cancer Center has been a leading site in the design and conduct of final trials involved with the approval of pacritinib, the first therapy specifically approved for myelofibrosis patients with low platelet counts, a condition called thrombocytopenia.

Patients with low platelets can have difficulties with enlarged spleen (splenomegaly), lower than normal numbers of blood cells (cytopenia) or risk of progressing to acute leukemia. These conditions may impact survival. About 21,000 patients in the U.S. have myelofibrosis and about a third of them suffer from thrombocytopenia.

“Pacritinib is an important addition to the armamentarium we have for treating patients with myelofibrosis, in particular because of the safety and effectiveness that has been seen for a subset of patients with myelofibrosis who have low platelet counts,” said Mesa, who served as principal investigator of the PERSIST 1 Global phase 3 trial of pacritinib.

The Mays Cancer Center has been a leading site in the design and conduct of final trials involved with the approval of pacritinib, the first therapy specifically approved for myelofibrosis patients with low platelet counts.

Oral pill improves care of patients with anemia

Mesa and Mays Cancer Center investigators are currently developing another myelofibrosis drug called momelotinib, pending FDA approval in 2023, that has shown to significantly improve outcomes of patients with anemia, a condition that reduces oxygen flow to the body’s organs.

In myelofibrosis, scar tissue forms in the bone marrow and hinders the body’s ability to produce healthy blood cells. Anemia, a lack of red blood cells to carry oxygen throughout the body, is observed in virtually all these patients and negatively impacts survival, Mesa said.

“A third of the patients have anemia up front, and most patients will develop it over the course of their disease,” Mesa said. Without anemia, median survival with myelofibrosis is about eight years, he added.

“For patients with severe anemia, survival is shortened to about two years. Even with mild anemia, the median survival is 4.9 years. A drug to treat anemia in these patients has been urgently needed,” Mesa said.

Findings were favorable in the MOMENTUM phase 3 randomized study evaluating momelotinib against a second medication, danazol, in symptomatic and anemic myelofibrosis patients previously treated with standard-of-care JAK inhibitor therapy. The study enrolled 195 myelofibrosis patients in 21 countries. Of those, 130 received momelotinib and 65 danazol. In the momelotinib group:

• All prespecified primary and key secondary endpoints were met.
• Significant improvements in symptoms, spleen size and anemia measures were observed.
• Favorable safety and a trend toward improved overall survival were documented.
• Participants required fewer transfusions to replace red blood cells and evidenced better oxygen-carrying hemoglobin levels.

“Findings support the future use of momelotinib as an effective treatment in MF patients, especially in those with anemia,” said Mesa.

Read more stories from our 2022 Annual Report.

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