What's New?

The article presents updated findings from the QUAZAR AML-001 trial, investigating the long-term survival outcomes of patients with acute myeloid leukemia (AML) in first remission after chemotherapy. The study focused on the efficacy of oral azacitidine (Oral-AZA) versus placebo in older patients ineligible for stem cell transplantation. Results revealed that Oral-AZA significantly prolonged overall survival and relapse-free survival compared to placebo. Patients receiving Oral-AZA demonstrated sustained survival benefits over five years, with higher survival rates at 3 and 5 years compared to placebo. Additionally, the study identified clinical and biological factors associated with long-term survival, highlighting the potential of Oral-AZA maintenance therapy for patients in remission after chemotherapy.

Geron Corporation has announced positive top-line results from its IMerge Phase 3 clinical trial of imetelstat, a telomerase inhibitor, for lower-risk myelodysplastic syndromes (MDS). The trial met its primary endpoint of 8-week transfusion independence (TI) and a key secondary endpoint of 24-week TI, both with highly statistically significant improvements. The median duration of TI approached one year for 8-week responders and 1.5 years for 24-week responders. Efficacy results were significant across key MDS subtypes, including varying transfusion burdens and IPSS risk categories. Safety results were consistent with previous trials, showing no new safety signals. Based on these results, Geron plans to submit regulatory applications in the U.S. and EU in 2023 and prepare for a potential U.S. commercial launch in 2024.

The article discusses the presentation of overall survival data for oral decitabine and cedazuridine (marketed as INQOVI®) in patients with myelodysplastic syndromes (MDS) and chronic myelomonocytic leukemia (CMML) harboring TP53 mutations. The Phase 3 ASCERTAIN trial revealed that patients with biallelic TP53 mutations achieved a median overall survival of 13 months, while the median overall survival in the overall study population was 32 months. These results suggest the potential utility of this oral hypomethylating agent in patients with MDS and CMML harboring TP53 mutations, which are typically associated with poor outcomes. The study underscores the importance of identifying patients who may benefit from this treatment option and highlights the ongoing efforts to address the unmet needs of these patient populations.

Bristol Myers Squibb announced positive topline results from the Phase 3 COMMANDS trial evaluating Reblozyl® (luspatercept-aamt) in the first-line treatment of adult patients with very low-, low- or intermediate-risk myelodysplastic syndromes (MDS) who require red blood cell (RBC) transfusions. The study met its primary endpoint, demonstrating a significant improvement in red blood cell transfusion independence (RBC-TI) with concurrent hemoglobin increase. The safety profile of Reblozyl was consistent with previous studies, with no new safety signals reported. Bristol Myers Squibb plans to present detailed results at an upcoming medical meeting and discuss them with health authorities. Reblozyl, developed through a collaboration with Merck, is a first-in-class therapeutic option for the treatment of anemia in patients with beta thalassemia and MDS.

Syros Pharmaceuticals has received a positive opinion from the European Medicines Agency (EMA) for orphan drug designation for tamibarotene in the treatment of myelodysplastic syndrome (MDS). Tamibarotene, currently in Phase 3 trials, aims to become the first therapy for RARA-positive patients with newly diagnosed higher-risk MDS. The EU designation follows a similar one granted by the U.S. FDA earlier this year. This designation offers regulatory and financial incentives for developing treatments for rare conditions. Syros Pharmaceuticals aims to advance its pipeline, leveraging small molecules to control gene expression effectively.

Gamida Cell's Biologics License Application (BLA) for omidubicel, an allogeneic hematopoietic stem cell transplant therapy for blood cancer patients, has been accepted by the FDA with Priority Review. Omidubicel demonstrated significant reduction in engraftment time compared to standard umbilical cord blood in Phase 3 trials. If approved, it could address the critical need for stem cell donors, potentially benefiting 2,000 - 2,500 patients annually in the U.S. The FDA's Prescription Drug User Fee Act (PDUFA) target action date is January 30, 2023. Gamida Cell is optimistic about omidubicel's potential and is committed to working with the FDA to expedite its availability.

The FDA has granted breakthrough therapy designation to Roche's Venclexta (venetoclax) in combination with azacitidine for previously untreated intermediate, high-, and very high-risk myelodysplastic syndromes (MDS). MDS, a rare group of blood cancers, often progress to acute myeloid leukemia (AML). With approximately 10,000 new cases yearly in the US, patients face a median survival of only 18 months with higher-risk MDS. This designation, based on interim phase Ib study results, expedites the development of medicines for serious conditions. Venclexta is already approved for certain AML treatments and is jointly developed and commercialized by AbbVie and Roche.

A new Molecular International Prognostic Scoring System (IPSS-M) for Myelodysplastic Syndromes (MDS) was developed, enhancing risk stratification and treatment planning based on genetic profiles. Developed through international collaboration, IPSS-M offers personalized risk scores and a web-based calculator for clinical use.