Dr Fleur-Lominy on Ongoing Research Within CML at the 2024 ASCO Annual Meeting

Shella Saint Fleur-Lominy, MD, PhD, assistant professor, Department of Medicine, program director, Hematology and Medical Oncology Fellowship, New York University Grossman School of Medicine, and Yan Leyfman, MD, internal medicine and clinical researcher, Mount Sinai, co-founder, executive director, MedNews Week, executive committee member, Music Beats Cancer, discuss ongoing research within the chronic myeloid leukemia (CML) patient population on 

Leyfman says that at the meeting, attendees saw exciting data from a late-breaking off-track presentation on the use of asciminib (Scemblix) compared with investigator-selected TKIs in patients with newly diagnosed CML, as seen in 

the phase 3 ASC4FIRST trial (NCT04971226)

. These results are exciting, Fleur-Lominy begins. The study met its primary end point, which is quite rare for a phase 3 study, Fleur-Lominy reports. Achievement of major molecular response (MMR) is particularly important for young patients, as achieving early, deep remissions means they may not need lifelong treatment, Fleur-Lominy notes. The ability to reach MMR early with asciminib is promising, and the biggest beneficiaries will be the patients receiving this agent, she explains.

Within CML, there is also a 4-year follow-up analysis of 

 which includes ponatinib in patients with chronic-phase CML harboring a 

 T315I mutation, Leyfman shares. Fleur-Lominy shares that these data are not surprising, as patients with 

 T315I mutations are resistant to first- and second-generation TKIs, leaving few treatment options. However, ponatinib (Iclusig) has been shown to be effective in this patient population, Fleur-Lominy notes. This study compared different doses of ponatinib in a 1:1:1 randomization, showing that patients who receive this agent can remain in long-term remission with good overall survival outcomes, she shares. The 45 mg dose of ponatinib was the most effective, though it was also associated with more toxicity than the other dose levels. However, patients who lost their response on a lower dose could still be salvaged by re-escalating to a higher dose, Fleur-Lominy concludes.

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Shella Saint Fleur-Lominy, MD, PhD, and Yan Leyfman, MD, discuss ongoing research within the chronic myeloid leukemia patient population. 

Dr Ben Levy and Dr Saint Fleur Discuss ASCO 2024 Data

Dr Levy and Dr Saint Fleur: On Location

OncLive® will be LIVE with OncLive® News Network: On Location at the 2024 ASCO Annual Meeting. Each day, we will broadcast a series of interviews with top thought leaders, to learn their thoughts and reactions to data presented across oncology during the conference.

Sifting Through Data in Lung Cancer and Leukemia: Drs Levy and Saint Fleur

Shella Saint Fleur-Lominy, MD, PhD, an assistant professor in the Department of Medicine at NYU Langone Health’s Perlmutter Cancer Center, discusses targeted pathways in myeloproliferative neoplasms (MPNs).

Some pathways are being targeted in the realm of MPNs, says Fleur-Lominy. More JAK1/2 inhibitors that are proving to be more selective, as was observed with fedratinib (Inrebic); however, others are also being tested. Epigenetic modulators are also available for these patients. Many pathways dependent or independent of STAT downstream are being targeted with therapies that are showing promising results, as well, adds Fleur-Lominy. Some of these therapies are being tested as single agents and others are being tested in combination with ruxolitinib (Jakafi), concludes Fleur-Lominy.

Shella Saint Fleur-Lominy, MD, PhD, discusses targeted pathways in myeloproliferative neoplasms.

Dr. Fleur-Lominy on Targeted Pathways in MPNs

Shella Saint Fleur-Lominy, MD, PhD, an assistant professor, Department of Medicine, at NYU Langone Health’s Perlmutter Cancer Center, discusses the current sequencing strategy in the treatment of patients with myeloproliferative neiplasms (MPNs).

In MPNs, if they are a transplant candidate, it is preferred to take them to transplant depending on the risk level, unless observation is appropriate, says Fleur-Lominy. Some patients can be observed because they are asymptomstic. However, when these patients start developing symptoms, transplant should not be delayed. Transplant should be the first option, and then a JAK inhibitor can be given later if the patient relapses or experiences disease progression, concludes Fleur-Lominy.

Shella Saint Fleur-Lominy, MD, PhD, discusses the current sequencing strategy in the treatment of patients with myeloproliferative neiplasms.

Dr. Fleur-Lominy on the Current Sequencing Strategy in MPNs

Shella Saint Fleur-Lominy, MD, PhD, an assistant professor, Department of Medicine, at NYU Langone Health’s Perlmutter Cancer Center, discusses remaining challenges in myelofibrosis.

Typically, patients with myelofibrosis are older and have existing comorbidities, says Saint Fleur-Lominy. Additionally, treatment options for these patients are associated with significant toxicities, explains Saint Fleur-Lominy.

Identifying better targets and more selective inhibitors may make treatment more tolerable for patients, says Saint Fleur-Lominy.

It is important to develop novel agents as the number of patients who are eligible for curative-intent hematopoietic stem cell transplantation is low, concludes Saint Fleur-Lominy.

Shella Saint Fleur-Lominy, MD, PhD, discusses remaining challenges in myelofibrosis.

Dr. Saint Fleur-Lominy on Remaining Challenges in Myelofibrosis

Shella Saint Fleur-Lominy, MD, PhD, an assistant professor, Department of Medicine, at NYU Langone Health’s Perlmutter Cancer Center, discusses the use of ruxolitinib (Jakafi) in the treatment of patients with myeloproliferative neoplasms (MPNs).

The track record with ruxolitinib supports its use over fedratinib (Inrebic) in the treatment of patients with MPNs, according to Saint Fleur-Lominy. At the moment, physicians have more experience with administering ruxolitinib, as it was approved for use in myelofibrosis since 2011, says Saint Fleur-Lominy. Thus, those working in the field are familiar with the agent and feel comfortable adjusting the dosage if a patient experiences cytopenia. Patients can still experience benefit from ruxolitinib at a lower dosage, says Saint Fleur-Lominy.

For these reasons, most will gravitate toward the use of ruxolitinib in practice. However, per the National Comprehensive Cancer Network guidelines, fedratinib is also considered to be an option for patients with high-risk myelofibrosis, concludes Saint Fleur-Lominy.

 Shella Saint Fleur-Lominy, MD, PhD, discusses the use of ruxolitinib (Jakafi) in the treatment of patients with myeloproliferative neoplasms.
 

Dr. Saint Fleur-Lominy on the Use of Ruxolitinib Versus Fedratinib in MPNs

Shella Saint Fleur-Lominy, MD, PhD, an assistant professor in the Department of Medicine at NYU Langone Health’s Perlmutter Cancer Center, discusses the role of transplant in myeloproliferative neoplasms (MPNs).

Currently, allogeneic stem cell transplant (allo-SCT) is the only curative option for patients with MPNs, says Saint Fleur-Lominy. JAK2 inhibitors can aid in symptom management to make patients more comfortable. Although there is some evidence that ruxolitinib (Jakafi) may also improve survival, the agent does not have a good disease-modifying effect.

Allo-SCT may be considered for patients with intermediate- or high-risk MPNs who don’t have significant comorbidities, says Saint Fleur-Lominy. The age of the patient could also influence transplant eligibility.

Eligible patients should be considered for transplant upfront, after which a JAK inhibitor can be considered upon relapse or progression. If a patient is asymptomatic, they can defer transplant until they develop symptoms, concludes Saint Fleur-Lominy.

Shella Saint Fleur-Lominy, MD, PhD, discusses the role of transplant in myeloproliferative neoplasms.

Dr. Saint Fleur-Lominy on the Role of Transplant in MPNs

Shella Saint Fleur-Lominy, MD, PhD, an assistant professor in the Department of Medicine at NYU Langone Health’s Perlmutter Cancer Center, discusses emerging agents in myeloproliferative neoplasms (MPNs).

Now that the field has a better understanding of the abnormal signals that occur in mutation-specific hematopoietic stem cells, more drugs are beginning to emerge, explains Saint Fleur-Lominy. For example, alisertib, which is an Aurora kinase A inhibitor, can reduce myelofibrosis in the bone marrow. In a phase I trial, alisertib led to a reduction in spleen size and improvement in symptoms similar to what is seen with JAK2 inhibitors. Out of 7 patients, 5 experienced a decrease in the amount of fibrosis that they had in the bone marrow, says Saint Fleur-Lominy.

A phase II study is evaluating the telomerase inhibitor telomeric oligonucleotide. Data demonstrated a slight reduction in spleen size and symptoms. Furthermore, investigators reported increased benefit with higher doses of the drug, adds Saint Fleur-Lominy.

Several other pathways, as well as the development of more specific JAK1/2 inhibitors, are under investigation, concludes Saint Fleur-Lominy.

Shella Saint Fleur-Lominy, MD, PhD, an assistant professor in the Department of Medicine at NYU Langone Health

Dr. Saint Fleur-Lominy on Emerging Agents in MPNs

Shella Saint Fleur-Lominy, MD, PhD, an assistant professor at NYU Langone Health’s Perlmutter Cancer Center, discusses the differences between ruxolitinib (Jakafi) and fedratinib (Inrebic) in myeloproliferative neoplasms (MPNs).

, says Saint Fleur-Lominy. However, the role of 

According to findings from the phase III JAKARTA which showed potential cases of Wernicke’s encephalopathy, the FDA placed a clinical hold on fedratinib, explains Saint Fleur-Lominy. The FDA lifted the clinical hold in August 2017 and fedratinib was subsequently approved in August 2019 for the treatment of patients with intermediate-2 or high-risk primary or secondary myelofibrosis.

Fedratinib is an alternative therapy for patients who cannot tolerate ruxolitinib due to significant cytopenia, says Saint Fleur-Lominy. Though cytopenia can occur with fedratinib, the risk of thrombocytopenia is decreased compared with ruxolitinib.

The risk of encephalopathy may deter some physicians from utilizing fedratinib in the clinic. However, measuring thiamine levels and monitoring patients carefully can lead to reduced risk, concludes Saint Fleur-Lominy.

Shella Saint Fleur-Lominy, MD, PhD, discusses the differences between ruxolitinib and fedratinib in the treatment of patients with myeloproliferative neoplasms. 


Dr. Saint Fleur-Lominy on Differences Between Ruxolitinib and Fedratinib in MPNs

Shella Saint Fleur-Lominy, MD, PhD, an assistant professor at NYU Langone Health’s Perlmutter Cancer Center, discusses the effects ruxolitinib (Jakafi) has on symptom burden in patients with myeloproliferative neoplasms (MPNs).

Ruxolitinib is used in patients with high- or intermediate-risk myelofibrosis who are not candidates for transplant, explains Saint Fleur-Lominy. Patients with any type of MPN have high symptom burden, with associated symptoms being splenomegaly, which causes discomfort, or abnormal signaling of cytokine that includes night sweats, fever, and low appetite, says Saint Fleur-Lominy.

Ruxlotinib helps reduce the spleen size and other symptom burden, leading to patients feeling more comfortable. Similarly, in polycythemia vera, ruxolitinib also causes a reduction in spleen size, a lower need for phlebotomy, and improvement in symptom burden, concludes Saint Fleur-Lominy.

Shella Saint Fleur-Lominy, MD, PhD, discusses the effects ruxolitinib has on symptom burden in patients with myeloproliferative neoplasms.

Shella Saint Fleur-Lominy, MD, PhD

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