Mikkael A. Sekeres, MD, discusses the results of combining luspatercept and lenalidomide in lower-risk, non–5q deletion myelodysplastic syndromes.

Dr Sekeres on Luspatercept Plus Lenalidomide in Non–5q Deletion MDS

Mikkael A. Sekeres, MD, professor of medicine, chief, Division of Hematology, Leukemia Section, University of Miami Health System, Sylvester Comprehensive Cancer Center, discusses safety and efficacy results from a phase 1b/2 study (NCT04539236) combining luspatercept-aamt (Reblozyl) and lenalidomide (Revlimid) in patients with lower-risk, non–5q deletion myelodysplastic syndromes. Sekeres and colleagues shared these results in a presentation at the 

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Dr Sekeres on Outcomes With Imetelstat in Transfusion-Dependent MDS

Mikkael A. Sekeres, MD, professor, medicine, chief, Division of Hematology, Leukemia Section, the University of Miami Sylvester Comprehensive Cancer Center, discusses a subgroup analysis investigating treatment with imetelstat (Rytelo) in patients with low-to-intermediate-1–risk myelodysplastic syndrome (MDS), highlighting the significance of 

This subgroup analysis assessed hemoglobin level improvements among patients responding to imetelstat, Sekeres begins. Investigators found that these patients achieved transfusion independence and experienced a significant increase in hemoglobin levels, averaging approximately 3 grams per deciliter, according to Sekeres. This substantial improvement underscores the drug’s efficacy in enhancing overall hematologic health in addition to reducing transfusion dependency, he reports.

Secondly, the analysis investigated whether these hematologic improvements were influenced by other factors, such as the use of growth factors or the need for platelet transfusions, Sekeres continues. The results showed that the improvements in hemoglobin levels and the achievement of transfusion independence were consistent regardless of whether patients required growth factors or had low platelet counts. This consistency indicates that imetelstat’s benefits extend broadly across various patient profiles, regardless of the presence of other hematologic abnormalities, he emphasizes.

These findings strongly support the use of imetelstat in this patient population, Sekeres elucidates. The demonstrated improvement in hemoglobin levels, in addition to achieving transfusion independence, bolsters the FDA’s approval of the drug for patients with lower-risk MDS who are transfusion dependent, he notes.

Moreover, these findings have important implications beyond immediate treatment outcomes, Sekeres expands. The ability of imetelstat to improve hemoglobin levels independently of other hematologic abnormalities indicates that it can be a versatile and reliable treatment option for a wide range of patients with lower-risk MDS, he says. This may lead to more personalized and effective treatment strategies, potentially improving the quality of life and clinical outcomes for many patients, Sekeres concludes.

Mikkael A. Sekeres, MD, discusses a subgroup analysis of treatment with imetelstat in patients with low-to intermediate-1–risk myelodysplastic syndrome.

, which provides oncology professionals with the resources and information they need to provide the best patient care. In both digital and print formats, 

 covers every angle of oncology practice, from new technology to treatment advances to important regulatory decisions.

In today’s episode, sponsored by Geron, we had the pleasure of speaking with Mikkael A. Sekeres, MD, about the FDA approval of imetelstat (Rytelo) for patients with lower-risk myelodysplastic syndrome (MDS) and transfusion-dependent anemia. Dr Sekeres is a professor of medicine and chief of the Division of Hematology in the Leukemia Section at the University of Miami Sylvester Comprehensive Cancer Center in Florida.

On June 6, 2024, the FDA approved imetelstat for the treatment of adult patients with low-to-intermediate-1–risk MDS and transfusion-dependent anemia requiring at least 4 red blood cell (RBC) units over 8 weeks who have lost response to, have not responded to, or are not eligible for erythropoiesis stimulating agents. This regulatory decision was based on data from the phase 3 IMerge trial (NCT02598661), in which patients treated with imetelstat (n = 118) had an 8-week RBC transfusion independence (RBC-TI) rate of 39.8% (95% CI, 30.9%-49.3%) compared with 15% (95% CI, 7.1%-26.6%) in those who received placebo (n = 59; 

In our exclusive interview, Dr Sekeres discussed the significance of this approval, key findings from IMerge, and how the use of imetelstat affects RBC-TI rates in the absence of platelet transfusions or myeloid growth factors in this patient population.

That’s all we have for today! Thank you for listening to this episode of 

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Dr Sekeres discusses the significance of the FDA approval of imetelstat for patients with lower-risk MDS and transfusion-dependent anemia.

FDA Approval Insights: Imetelstat in Lower-Risk MDS and Transfusion-Dependent Anemia

Dr Sekeres on Outcomes from the ASTREON Trial in Low- to Intermediate-Risk MDS 

Mikkael A. Sekeres, MD, professor, medicine, chief, Division of Hematology, Leukemia Section, the University of Miami Sylvester Comprehensive Cancer Center, discusses preliminary safety and efficacy findings with oral azacitidine (Vidaza) in patients with low- to intermediate-risk myelodysplastic syndromes (MDS), as reported in the phase 2/3 ASTREON trial (NCT05469737).

. ASTREON trial examined patients with low-to-intermediate-risk MDS who were treated with oral azacitidine at doses of either 200 mg or 300 mg daily, Sekeres begins. Patients were randomly assigned to receive 1 of these dosing regimens, he adds. The study revealed that the 200-mg and 300-mg doses were equally effective, eliciting similar response rates, Sekeres reports. Specifically, between approximately one-quarter and one-third of the patients achieved red blood cell (RBC) transfusion independence. This means that these patients, who started the study dependent on RBC transfusions due to anemia, no longer needed transfusions for at least an 8-week period after being treated with the drug, he emphasizes.

Moreover, the trial found that the adverse effects (AEs) associated with both dosing levels were consistent with expectations and are likely less severe than those observed when azacitidine is administered intravenously (IV) or subcutaneously for 7 days, he notes. This indicates that the oral form of the drug may offer a more favorable AE profile, Sekeres says.

Overall, Sekeres states that the trial demonstrated that oral azacitidine is effective, well tolerated, and more convenient compared with IV or subcutaneous administration. The ability to take the medication in pill form is a significant advantage, simplifying the treatment process for patients and potentially improving adherence to the therapy, he reports. This finding is particularly important for patients who rely on regular RBC transfusions, as achieving transfusion independence can greatly enhance their quality of life, Sekeres concludes.

Mikkael A. Sekeres, MD, discusses preliminary outcomes with oral azacitidine in lower-risk myelodysplastic syndromes, as reported in the ASTREON trial.

Dr Sekeres on the FDA Approval of Imetelstat in Lower-Risk MDS With Anemia

Mikkael A. Sekeres, MD, professor, medicine, chief, Division of Hematology, Leukemia Section, the University of Miami Sylvester Comprehensive Cancer Center, discusses the significance of the FDA approval of imetelstat (Rytelo) for patients with lower-risk myelodysplastic syndromes (MDS) and transfusion-dependent anemia.

 for the treatment of adult patients with low-to-intermediate-1–risk MDS and anemia requiring at least 4 red blood cell (RBC) units over 8 weeks who have lost response to, not responded to, or are not eligible for erythropoiesis-stimulating agents (ESAs). This regulatory decision was supported by data from the phase 2/3 IMerge trial (NCT02598661), which demonstrated that 39.8% (95% CI, 30.9%-49.3%) of patients in the imetelstat arm (n = 118) achieved RBC transfusion independence at week 8 vs 15% (95% CI, 7.1%-26.6%) of those in the placebo arm (n = 59; 

The FDA approval of imetelstat for patients with transfusion-dependent, lower-risk MDS expands the already-sparse treatment paradigm for this patient population, Sekeres says. Patients with lower-risk MDS with anemia typically receive ESAs, followed by lenalidomide (Revlimid) in those with deletion 5q gene mutations, Sekeres explains. 

luspatercept-aamt (Reblozyl) received FDA approval

 for the frontline treatment of anemia in adult patients with lower-risk MDS who may require regular RBC transfusions and have not received prior ESAs. Luspatercept was previouslyapproved by the FDA in 2020 for the treatment of anemia 

in adult patients with lower-risk MDS with ring sideroblasts

 who progressed on an ESA and require at least 2 RBC units over 8 weeks. However, luspatercept is most effective in patients with either a spliceosome mutation or ring sideroblasts, Sekeres emphasizes. For patients who do not have spliceosome mutations, ring sideroblasts, or deletion 5q gene mutations, the standard of care has been HMAs. Imetelstat expands the treatment arsenal for these patients, and can be given before or after HMA exposure, Sekeres concludes.

Mikkael A. Sekeres, MD, discusses the significance of the FDA approval of imetelstat for patients with lower-risk MDS and transfusion-dependent anemia.

Mikkael A. Sekeres, MD, vice-chair for Clinical Research and director of the Leukemia Program at Cleveland Clinic Taussig Cancer Institute, discusses staging patients with myelodysplastic syndromes (MDS).

When considering available treatments for patients with MDS, the first thing to examine is whether they have lower- or higher-risk disease, says Sekeres. This is done through the use of the International Prognostics Scoring System (IPSS), particularly the revised version, which is generally the default staging system for MDS. This process used to be fairly straight forward: A patient’s risk assessment was based on their blood counts, blast percentage in their bone marrow, and their cytogenetics, explains Sekeres. Patients who have a lot of cytopenias also have a relatively high blast percentage of above 5%, but this can be up to 19%, Sekeres notes. Those who have poor-risk cytogenetics, particularly those who have complex cytogenetics, fall into higher-risk categories. 

Now, molecular typing has thrown a wrench into the system, according to Sekeres. Patients who might be classified as having lower-risk MDS using the IPSS or its revised version could have poor-risk molecular profiles that might include, for example, p53.

With higher-risk MDS, no matter how it is defined, the standard of care is usually a hypomethylating agent (HMA), which can be either azacitidine or decitabine, says Sekeres. More recently, an oral version of decitabine has been approved and appears to have activity that is equivalent to azacitidine or decitabine. However, no head-to-head comparisons have been made among the available HMAs, concludes Sekeres.

Mikkael A. Sekeres, MD, discusses staging patients with myelodysplastic syndromes.

Dr. Sekeres on Staging Low- Versus High-Risk MDS

Mikkael A. Sekeres, MD, professor of medicine, director, Leukemia Program, Cleveland Clinic Taussig Cancer Institute, discusses the need for novel combinations in higher-risk myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) and low-blast acute myelogenous leukemia (LB AML).

Patients with higher-risk MDS/CMML and oligoblastic AML (less than 30% blasts) typically receive 1 of 2 treatment regimens: intensive induction chemotherapy or less intensive treatment with a hypomethylating agent. High-intensity treatment has a high treatment-related mortality rate and is cumbersome for older patients with comorbidities, says Sekeres, and less intensive treatment with azacitidine alone results in relatively low and short-lived responses.

As such, investigators launched a phase 2 trial (NCT02610777) which evaluated the addition of pevonedistat, the first and only small-molecule inhibitor of the NEDD8-activating enzyme, to azacitidine in patients with higher-risk MDS/CMML and LB AML. The results were presented in an oral presentation at the 2020 ASCO Virtual Scientific Program.

Mikkael A. Sekeres, MD, discusses the need for novel combinations in higher-risk myelodysplastic syndrome (MDS)/chronic myelomonocytic leukemia (CMML) and low-blast acute myelogenous leukemia (LB AML).

Mikkael A. Sekeres, MD

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