Mikkael A. Sekeres, MD, MS, discusses the background on the FDA approval of momelotinib (Ojjaara) for the treatment of patients with anemic myelofibrosis.

Dr Sekeres on the Rationale for the FDA Approval of Momelotinib in Myelofibrosis

Mikkael A. Sekeres, MD, MS, professor, medicine, chief, Division of Hematology, Leukemia Section, the University of Miami Health System, Sylvester Comprehensive Cancer Center, 

discusses the background on the FDA approval of momelotinib

 (Ojjaara) for the treatment of patients with anemic myelofibrosis.

® State of the Science Summit™ on hematologic malignancies, Sekeres and colleagues provided updates in the realm of myelodysplastic syndromes. Notably, one of these updates includes the 

 for the treatment of adult patients with intermediate or high-risk myelofibrosis with anemia. Originally, the phase 3 SIMPLIFY-1 (NCT01969838) and SIMPLIFY-2 (NCT02101268) trials investigated momelotinib compared with ruxolitinib (Jakafi) and momelotinib compared with best available therapy, respectively, Sekeres begins. In SIMPLIFY-2, although patients receiving momelotinib didn't show a significant improvement in spleen response, they experienced a notable enhancement in symptom score, a benefit that is crucial for patients with myelofibrosis, he reports.

Subsequently, the phase 3 MOMENTUM trial (NCT04173494) was initiated, randomly assigning symptomatic patients with myelofibrosis in a 2:1 ratio to receive either momelotinib or danazol. Notably, significant improvement in symptom scores was observed with momelotinib, Sekeres states, saying that furthermore, substantial improvement in spleen size reduction was noted, forming the basis for momelotinib's FDA approval. Additionally, there was a trend toward enhanced red blood cell transfusion independence rates among patients, Sekeres adds.

 unveiled results from phase 3 trials exploring combination therapies, he expands. The phase 3 MANIFEST-2 trial (NCT04603495) evaluating pelabresib (CPI-0610) plus ruxolitinib vs placebo plus ruxolitinib in patients with myelofibrosis, showcased significant spleen shrinkage and a borderline significant enhancement in symptom scores, Sekeres states. Meanwhile, the phase 3 TRANSFORM-1 trial (NCT04472598) investigating navitoclax plus ruxolitinib vs ruxolitinib alone in patients with myelofibrosis demonstrated significant spleen size reduction with the combination, though no significant improvement in total symptom scores was observed.

Overall, these findings indicate an evolving myelofibrosis treatment paradigm, ushering in the era of combination therapy with promising prospects yet to be fully realized, Sekeres concludes.

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Mikkael A. Sekeres, MD, MS, discusses the background on the FDA approval of momelotinib for the treatment of patients with anemic myelofibrosis.

Mikkael A. Sekeres, MD, MS, discusses the utility of myelodysplastic syndromes risk stratification systems. 

Dr Sekeres on Using MDS Risk-Stratification Systems in Clinical Practice

Mikkael A. Sekeres, MD, MS, professor, medicine, chief, Division of Hematology, Leukemia Section, the University of Miami Health System and Sylvester Comprehensive Cancer Center, discusses the utility of myelodysplastic syndromes (MDS) risk-stratification systems.

 State of the Science Summit™ on hematologic malignancies, Sekeres and colleagues provided updates in the realm of MDS. The recent updates to MDS risk-stratification systems have had notable implications for treatment selection within this domain, as highlighted in the meeting, Sekeres begins. Various abstracts presented at the 

 scrutinized different classification systems and assessed the accuracy of the IPSS-Molecular (IPSS-M) model in predicting outcomes. Initially, either the IPSS-revised or the IPSS-M stratification systems are employed to stratify patients into lower-risk or higher-risk MDS categories, Sekeres explains, thereby guiding treatment urgency and therapeutic options.

In terms of therapeutic advancements in MDS, recent clinical data have shed light on luspatercept-aamt (Reblozyl), Sekeres continues. Originally 

for patients exhibiting ring sideroblasts linked with MDS

 post-exposure to an erythropoiesis stimulating agent (ESA), luspatercept demonstrated promising results in the phase 3 MEDALIST trial (NCT02631070), he reports. 

Further insights emerged from the phase 3 COMMANDS trial

 (NCT03682536), which compared upfront luspatercept with ESAs in patients with anemia due to lower-risk MDS who require red blood cell (RBC) transfusions, Sekeres elucidates. Results revealed significantly improved response rates and prolonged response durations with luspatercept, particularly among patients with ring sideroblasts or the 

 mutation, prompting consideration of luspatercept as a first-line option or as subsequent therapy following ESA progression in these patient subsets, he notes.

Furthermore, findings from the phase 2/3 IMerge trial (NCT02598661) demonstrated substantial rates of RBC transfusion independence among patients receiving imetelstat compared with placebo recipients, he states. The imminent FDA decision on imetelstat's approval, anticipated in 2024, holds potential to introduce another treatment avenue for patients with lower-risk MDS, Sekeres concludes.

Mikkael A. Sekeres, MD, MS, discusses the utility of myelodysplastic syndromes risk stratification systems.

Mikkael A. Sekeres, MD, MS, professor of Medicine, director, Leukemia Program, Cleveland Clinic Taussig Cancer Institute, discusses a study examining azacitidine combined with lenalidomide or with vorinostat versus azacitidine monotherapy in higher-risk patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML).

The randomized phase II North American Intergroup SWOG S1117 study enrolled 277 patients. Results showed that the combination therapies in both groups of patients were well tolerated; there was no difference regarding neutropenia and fever. Patients who received lenalidomide/azacitidine were more likely to develop rash, while patients in the vorinostat/azacitidine arm were more likely to experience gastrointestinal toxicities. However, patients who received either combination regimens were significantly more likely to have dose-reductions not specified by protocol, Sekeres explains.

For patients with MDS who were in the lenalidomide/azacitidine arm, the overall response rate (ORR) was 49% compared with 38% with azacitidine monotherapy (

 = .16). Patients who received vorinostat/azacitidine had a lower ORR versus azacitidine monotherapy.

However, in patients with CMML, ORR with azacitidine/lenalidomide was 68% compared with 29% for azacitidine monotherapy. These findings demonstrate that though there are no statistically significant findings in high-risk patients with MDS, it was found to be significant for patients with CMML, Sekeres adds.

Mikkael A. Sekeres, MD, MS, professor of Medicine, director, Leukemia Program, Cleveland Clinic Taussig Cancer Institute, discusses a study examining azacitidine combined with lenalidomide or with vorinostat versus azacitidine monotherapy in higher-risk patients with myelodysplastic syndromes and chronic myelomonocytic leukemia.


Mikkael A. Sekeres, MD, MS

Articles

Dr Sekeres on the Rationale for the FDA Approval of Momelotinib in Myelofibrosis

Dr Sekeres on Using MDS Risk-Stratification Systems in Clinical Practice

Dr. Sekeres on Combination Therapies With Azacitidine in CMML and MDS