© 2023 HSP News Service, L.L.C.
Myelodysplastic syndromes (MDS) are a heterogeneous group of clonal hematopoietic stem cell disorders that are characterized by ineffective hematopoiesis, resulting in cytopenias, and they carry a risk of progression to acute myeloid leukemia (AML). In 2022, the fifth edition of the World Health ...
On October 24, the U.S. Food and Drug Administration (FDA) approved ivosidenib (Tibsovo) for adult patients with relapsed or refractory myelodysplastic syndromes (MDS) with a susceptible isocitrate dehydrogenase-1 (IDH1) mutation, as detected by an FDA-approved test. The FDA also approved the...
In a genetic analysis from the Blood and Marrow Transplant Clinical Trials Network 1102 Study reported in the Journal of Clinical Oncology, Versluis et al found that allogeneic hematopoietic cell transplantation (HCT) improved overall survival compared with non-HCT treatment in patients with...
On August 28, the U.S. Food and Drug Administration (FDA) approved luspatercept-aamt (Reblozyl) to treat anemia in adult patients with very low– to intermediate-risk myelodysplastic syndromes (MDS) who may require regular red blood cell transfusions and who have not received previous...
Investigators have identified a need for strong coordination between clinicians and skilled pathologists to ensure accurate, timely diagnosis of myelodysplastic syndromes (MDS). The study findings were recently published by Gorak et al in Blood Advances. Background MDS—a collection of chronic...
As presented at the 2023 ASCO Annual Meeting, the phase III IMerge trial of imetelstat1 and the phase III COMMANDS trial of luspatercept2 met their primary endpoints of transfusion independence. The findings suggest that lower-risk patients with transfusion-dependent, non-del(5q) myelodysplastic...
In the primary analysis of the phase III randomized, double-blind, placebo-controlled IMerge trial, in those achieving the primary endpoint of 8-week transfusion independence, treatment with imetelstat significantly reduced transfusion dependence—for a median duration of 1 year—and improved a...
Aaron T. Gerds, MD, of Cleveland Clinic Taussig Cancer Institute, talks about treating the anemia many patients with myelofibrosis experience because of JAK inhibitor therapy. The ACE-536-MF-001 study showed that luspatercept improved anemia and transfusion burden in this population, with a safety profile consistent with that in previous studies (Abstract 7016).
Interim results of a phase II study (EQOL-MDS) reported in the Journal of Clinical Oncology by Oliva et al showed that eltrombopag, an orally bioavailable small molecule acting as a thrombopoietin receptor agonist, significantly increased the rate of platelet response vs placebo in patients with...
Amer Methqal Zeidan, MBBS, MHS, of Yale University and Yale Cancer Center, discusses phase III findings on the first-in-class telomerase inhibitor imetelstat, which was given to patients with heavily transfusion-dependent non-del(5q) lower-risk myelodysplastic syndromes that are resistant to erythropoiesis-stimulating agents. Imetelstat resulted in a significant and sustained red blood cell (RBC) transfusion independence in 40% of these heavily transfused patients. The response was also durable and accompanied by an impressive median hemoglobin rise of 3.6 g/dL, and seen in patients with and without ring sideroblasts. Importantly, reduced variant allele frequency was observed in the most commonly mutated myeloid genes which correlated with duration of transfusion independence and hemoglobin rise, therefore suggesting a disease-modifying potential of this agent (Abstract 7004).
Guillermo Garcia-Manero, MD, of The University of Texas MD Anderson Cancer Center, discusses phase III findings from the COMMANDS trial. Compared with epoetin alfa, luspatercept improved red blood cell transfusion independence and erythroid response, as well as the duration of response in erythropoiesis-stimulating agent–naive, transfusion-dependent patients with lower‐risk myelodysplastic syndromes (Abstract 7003).
Patients with lower-risk myelodysplastic syndromes (MDS) who received luspatercept to treat anemia instead of erythropoiesis-stimulating agents (ESAs)—the current standard of care—needed fewer blood transfusions and clinic visits. These findings from the phase III COMMANDS trial were presented by...
In a European study reported in the Journal of Clinical Oncology, Sauta et al found that the recently devised Molecular International Prognostic Scoring System (IPSS-M) had improved prognostic ability vs the standard Revised International Prognostic Scoring System (IPSS-R) in patients with...
In a phase Ib trial (5F9005) reported in the Journal of Clinical Oncology, David A. Sallman, MD, and colleagues found that the combination of magrolimab and azacitidine showed activity in previously untreated patients with intermediate- to very high–risk myelodysplastic syndromes (MDS). As stated...
Researchers have discovered that vitamin B5 in combination with existing drugs may be the key to improving outcomes in patients with myelodysplastic syndromes (MDS) and ineffective red blood cell production, according to a novel study published by Mian et al in Science Translational Medicine....
In a study reported in JAMA Oncology, McDonald et al found that receipt of blood or marrow transplantation (BMT) was associated with an increased risk of subsequent malignant neoplasms of the gastrointestinal (GI) tract. As stated by the investigators, “Survivors of BMT are at increased risk of...
Positive results were announced from the phase III IMerge trial (ClinicalTrials.gov identifier NCT02598661) evaluating the first-in-class telomerase inhibitor imetelstat in patients with lower-risk myelodysplastic syndromes (MDS) who are relapsed, refractory, or ineligible for...
In a long-term follow-up of the German phase II PACE-MDS trial reported in the Journal of Clinical Oncology, Uwe Platzbecker, MD, and colleagues described erythroid, neutrophil, and platelet hematologic improvement rates with luspatercept treatment for anemia in patients with lower-risk...
On August 26, the U.S. Food and Drug Administration (FDA) approved pemigatinib (Pemazyre), a selective fibroblast growth factor receptor (FGFR) inhibitor, for the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangement. Myeloid/lymphoid neoplasms with...
As reported in NEJM Evidence by Sasaki et al, extended follow-up of a phase II trial showed good outcomes with low doses of the hypomethylating agents decitabine and azacitidine in previously untreated patients with lower-risk myelodysplastic syndromes (MDS). Study Details The study included 113...
In a phase II trial reported in the Journal of Clinical Oncology, Mishra et al found that maintenance treatment with the first-in-class small-molecule p53 reactivator eprenetapopt plus azacitidine following allogeneic hematopoietic stem cell transplantation (HSCT) was associated with “encouraging”...
In a study reported in The New England Journal of Medicine, Liu et al found that hypomethylating therapy was associated with upregulation of the oncogene SALL4 in a high proportion of patients with myelodysplastic syndrome. They also identified the gene region that is demethylated and responsible...
Mutations in SF3B1 and U2AF1 can drive overexpression of activated IRAK4—which regulates inflammation and promotes cancer cell growth and survival—and are associated with a poor prognosis for patients with high-risk myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Emavusertib is a...
Ruben A. Mesa, MD, of Mays Cancer Center at UT Health San Antonio MD Anderson Cancer Center, discusses new findings from the MOMENTUM study. This trial showed that in symptomatic and anemic patients with myelofibrosis, momelotinib was superior to danazol for symptom and spleen responses, as well as transfusion requirements (Abstract 7002).
“The value of experience is not in seeing much, but in seeing wisely.” —Sir William Osler To complement The ASCO Post’s continued comprehensive coverage of the 2021 American Society of Hematology (ASH) Annual Meeting & Exposition, here are several abstracts selected from the meeting...
Researchers have discovered that treatment resistance in patients with myelodysplastic syndromes (MDS) may be caused by two distinct classes of stem cells and identified possible therapeutic approaches that target these cells. Their findings, which could have significant benefits for patients with...
The phase III PANTHER trial, which evaluated pevonedistat plus azacitidine vs azacitidine alone in higher-risk myelodysplastic syndromes, chronic myelomonocytic leukemia, and low–blast count acute myeloid leukemia (AML) failed to meet its primary endpoint of event-free survival,1 though lessons...
The phase III PANTHER trial, which evaluated pevonedistat plus azacitidine vs azacitidine alone in higher-risk myelodysplastic syndromes, chronic myelomonocytic leukemia, and low–blast count acute myeloid leukemia (AML), failed to meet its primary endpoint of event-free survival, though lessons...
Alba Rodriguez-Meira, DPhil, of the University of Oxford, discusses a comprehensive analysis of the genetic, cellular, and molecular landscape of TP53-mediated transformation, providing insights into the evolution of chronic hematologic malignancies toward an aggressive acute leukemia. Because TP53 is the most commonly mutated gene in human cancer, these findings may well be of broad relevance (Abstract 3).
In separate analyses of 257 patients with acute leukemia or myelodysplastic syndrome (MDS) who developed COVID-19 and are part of the American Society of Hematology (ASH) RC COVID-19 Registry for Hematology, both neutropenia and having active MDS or leukemia (vs being in remission) were found to...
In one of the largest studies to date of the antibody response to vaccination against COVID-19 in people who had been treated for acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS), patients responded well to two doses of the Moderna mRNA vaccine and saw a pronounced increase in levels ...
As reported in the Journal of Clinical Oncology, Aziz Nazha, MD, and colleagues have developed a model for predicting the risk of disease progression for individual patients with myelodysplastic syndromes (MDS). To develop the prediction model for overall survival and leukemic transformation,...
In the German phase II VidazaAllo study reported in the Journal of Clinical Oncology, Kröger et al found that switching from azacitidine to reduced-intensity conditioning allogeneic hematopoietic stem cell transplantation (HSCT) contingent upon donor availability was associated with better outcomes ...
Recently, the U.S. Food and Drug Administration (FDA) granted special designation status to treatments for myelodysplastic syndromes and advanced triple-negative breast cancer. Breakthrough Therapy Designation for Venetoclax in Combination With Azacitidine for Myelodysplastic Syndromes Venetoclax...
In a study reported in the Journal of Clinical Oncology, Nakamura et al found that use of reduced-intensity conditioning allogeneic hematopoietic cell transplantation (HCT) in older patients with advanced myelodysplastic syndrome (MDS) with an available matched donor improved overall survival vs...
To complement The ASCO Post’s comprehensive coverage of the 2020 American Society of Hematology (ASH) Annual Meeting & Exposition, here are several abstracts selected from the meeting proceedings focusing on novel clinical trial findings in myelodysplastic syndromes (MDS). For full details of...
In a phase III trial reported in the Journal of Clinical Oncology, Guillermo Garcia-Manero, MD, and colleagues found that oral azacitidine significantly improved red blood cell (RBC) transfusion independence vs placebo in patients with lower-risk myelodysplastic syndromes. An increase in early...
In a study reported in the Journal of Clinical Oncology, Bersanelli et al reported that researchers in the EuroMDS Project found that patients with myelodysplastic syndromes (MDS) could be classified into eight distinct subtypes based on genomic characteristics. They also developed a new prognostic ...
In a study reported in The New England Journal of Medicine, Duncavage et al found that whole-genome sequencing in patients with acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS) provided rapid genomic profiling that improved diagnostic yield vs conventional cytogenetic analysis, as...
In a Groupe Francophone des Myélodysplasies phase II study reported in the Journal of Clinical Oncology, Cluzeau et al found that the combination of eprenetapopt and azacitidine produced high response rates in previously untreated patients with high-risk TP53-mutated myelodysplastic syndromes (MDS) ...
Stem cell transplants are not frequently offered to older patients with high-risk myelodysplastic syndromes (MDS). According to a study from the Blood and Marrow Transplant Clinical Trials Network (BMTCTN 1102), these patients may indeed achieve a survival benefit from stem cell transplant. As...
In a phase Ib/II study reported in the Journal of Clinical Oncology, David A. Sallman, MD, and colleagues found that the combination of azacitidine and the first-in-class small-molecule agent eprenetapopt produced high response rates in patients with TP53-mutant myelodysplastic syndromes (MDS)....
In a phase III U.S. Intergroup trial reported in the Journal of Clinical Oncology, Alan F. List, MD, and colleagues found that treatment with lenalidomide plus epoetin alfa increased the rate of major erythroid response vs lenalidomide alone in patients with lower-risk, non-del(5q) myelodysplastic...
In the phase II FIGARO trial reported in the Journal of Clinical Oncology, Craddock et al found that intensified reduced-intensity conditioning with fludarabine/amsacrine/cytarabine–busulfan (FLAMSA-Bu) did not improve outcomes following allogeneic stem cell transplantation vs standard...
The BCL2 inhibitor venetoclax can be safely added to standard therapies for some high-risk myeloid blood cancers, and in early studies, the combination showed improved outcomes, according to two reports presented by Jacqueline S. Garcia, MD, and colleagues at the 2020 American Society of Hematology ...
Stem cell transplants are not frequently offered to older patients with high-risk myelodysplastic syndromes (MDS). According to a study from the Blood and Marrow Transplant Clinical Trials Network (BMTCTN 1102), these patients may indeed achieve a survival benefit from stem cell transplant. As...
Corey Cutler, MD, MPH, of Dana-Farber Cancer Institute, discusses results from a multicenter trial that compared reduced-intensity allogeneic hematopoietic cell transplantation to hypomethylating therapy or best supportive care in patients aged 50 to 75 with advanced myelodysplastic syndromes (Abstract 75).
In the phase II portion of the phase II/III MDS3001 study reported in the Journal of Clinical Oncology, David P. Steensma, MD, and colleagues found that imetelstat—a first-in-class competitive inhibitor of telomerase enzymatic activity—markedly reduced the need for red blood cell transfusion in...
Patients with lower-risk myelodysplastic syndromes (MDS) who are dependent on red blood cell transfusions have limited options, especially if they are no longer responding to erythropoiesis-stimulating agents. Research presented during the virtual edition of the 25th European Hematology Association ...
Over the past few weeks, the U.S. Food and Drug Administration (FDA) has issued designations and accepted applications for novel agents, as well as approved companion diagnostics. We summarize these regulatory movements below. Breakthrough Therapy Designation for MK-6482 in von Hippel-Lindau...