- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Journal: Thalassemia in Japan (Pubmed Central) - Sep 10, 2021
Acquired α-thalassemia exists in exceptional cases, and cases of myelodysplastic syndrome with acquired Hemoglobin H disease have been reported as α-thalassemia myelodysplastic syndrome. Recent trials using a novel therapeutic agent, luspatercept, for transfusion-dependent β-thalassemia revealed that luspatercept safely and significantly reduces the transfusion volume.
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
[VIRTUAL] Efficacy and Safety of Luspatercept in Patients with Anemia: A Systematic Review () - Sep 6, 2021 - Abstract #SOHO2021SOHO_563;
High-dose luspatercept has shown promising results in terms of erythroid response, measured as either a reduction in transfusion burden or a mean increase in hemoglobin levels. A number of clinical trials are ongoing to assess its efficacy in myelofibrotic disorders to further extend its usage.
- |||||||||| Revlimid (lenalidomide) / BMS
[VIRTUAL] Treatment of Higher-Risk MDS () - Sep 6, 2021 - Abstract #SOHO2021SOHO_372;
P3
There are currently a number of phase IIitrials evaluating novel combinations in higher-risk MDS, including HMA combined with pevonedistat (NCT03268954); APR-246 in TP53-mutant MDS (NCT03745716)’; the anti-TIM3 antibody MBG453 (NCT04266301); the anti-CD47 antibody magrolimab (NCT04313881); and venetoclax (NCT04401748). New active agents to add to the treatment repertoire would be welcome and may allow for new approaches to disease, including different strategies at diagnosis, for consolidation of response, and in the maintenance setting.
- |||||||||| Revlimid (lenalidomide) / BMS
[VIRTUAL] Treatment of Lower Risk Myelodysplastic Syndromes MDS () - Sep 6, 2021 - Abstract #SOHO2021SOHO_371;
Recent intriguing data suggest earlier therapy with lower dose lenalidomide and for limited duration is associated with longer time to transfusion dependency and high cytogenetic response rate...For LR-MDS patients with ring sideroblast subtypes (RS), luspatercept was approved for treating anemia, first drug approval in a decade for MDS...Hypomethylating agents (HMAs) (azacitidine and decitabine) should be reserved for patients with higher risk disease features, later in disease course, or with bi/pancytopenia especially if later patients are not candidates for IST...demonstrated encouraging activity in phase Iiclinical study and currently being tested in phase IIirandomized clinical trial. Early intervention studies targeting inflammation are also in progress.
- |||||||||| Review, Journal: Current and emerging strategies for management of myelodysplastic syndromes. (Pubmed Central) - Sep 5, 2021
Targeted therapies approved for acute myeloid leukemia treatment, such as isocitrate dehdyrogenase inhibitors and venetoclax, are also being studied for use in MDS. In this review, we provide a brief overview of pathogenesis and current treatment strategies in MDS followed by a discussion of newer agents that are under clinical investigation.
- |||||||||| Reblozyl (luspatercept-aamt) / BMS, Merck (MSD)
Enrollment open, Enrollment change, Trial completion date: A Study to Evaluate the Efficacy, Drug Levels and Safety of Luspatercept (ACE-536) for the Treatment of Anemia Due to IPSS-R Very Low, Low, or Intermediate Risk Myelodysplastic Syndromes in Chinese and Japanese Participants With Ring Sideroblasts Who Require Red Blood Cell Transfusions (clinicaltrials.gov) - Aug 12, 2021
P2, N=40, Recruiting,
These results provide a positive benefit-risk profile for the titration-to-response dose regimen (1.0-1.75 mg/kg) recommended for this population. Not yet recruiting --> Recruiting | N=30 --> 40 | Trial completion date: Aug 2023 --> Feb 2026
- |||||||||| IMR-687 / Imara, Inc, VIT-2763 / Vifor, Reblozyl (luspatercept-aamt) / Acceleron, BMS
Review, Journal: Novel Therapeutic Advances in β-Thalassemia. (Pubmed Central) - Jul 4, 2021
Another therapeutic approach is to target the dysregulation of iron homeostasis, using, for example, hepcidin agonists (inhibitors of TMPRSS6 and minihepcidins) or ferroportin inhibitors (VIT-2763). This review provides an update on the novel therapeutic options that are presently in development at the clinical level in β-thalassemia.
- |||||||||| Oxbryta (voxelotor) / Global Blood Therap, Adakveo (crizanlizumab) / Novartis, Reblozyl (luspatercept-aamt) / Acceleron, BMS
Review, Journal: Innovative Treatments for Rare Anemias. (Pubmed Central) - Jun 8, 2021
L-glutamine, voxelotor, and crizanlizumab are new drugs approved SCD, targeting different steps of the complex pathophysiological mechanism...Interestingly, several molecules that showed promising results for treating one of these disorders are now under evaluation in the others. In the near future, the management of RA will probably consist of polypharmacotherapy tailored to patients' characteristics.
- |||||||||| [VIRTUAL] Management Strategies for MDS () - Jun 5, 2021 - Abstract #ASCO2021ASCO_5870;
In the near future, the management of RA will probably consist of polypharmacotherapy tailored to patients' characteristics. Design, eligibility criteria and key endpoints of the ASTX727-01-B and ASTX727-02 (ASCERTAIN) studies evaluating the oral combination of decitabine and cedazuridine for patients with MDS Response rates, duration of response and rates of transfusion independence achieved with oral decitabine/cedazuridine; FDA approval and current clinical role opposite standard IV decitabine Key efficacy and safety endpoints achieved in the randomized Phase III MEDALIST trial leading to the FDA approval of luspatercept for the management of MDS-associated anemia; optimal patient selection for and timing of therapy Activity observed with approved AML therapies (eg, venetoclax, ivosidenib, enasidenib, CC-486) in patients with MDS; current off-protocol role Magrolimab for MDS: Mechanism of action, available data, FDA breakthrough therapy designation and potential clinical role; activity in patients with AML Biologic rationale for the investigation of pevonedistat in combination with azacitidine for patients with higher-risk MDS; FDA breakthrough therapy designation for pevonedistat, ongoing evaluation and potential clinical role
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
[VIRTUAL] Navigating Myelodysplastic and Myelodysplastic/Myeloproliferative Overlap Syndromes () - Jun 5, 2021 - Abstract #ASCO2021ASCO_5737;
The advent of next-generation sequencing has allowed us to differentiate and classify these neoplasms with greater accuracy, albeit always in the context of an accurate morphologic diagnosis; in particular, accurate interpretation of dygranulopoiesis is important in diagnosing atypical CML, whereas correct estimation of blasts and promonocytes (regarded as blast equivalents) is important in risk-stratifying CMML. Although no gene mutations are specific for any MDS/MPN overlap subtype, the availability of sequencing results aids diagnostic accuracy, helps with risk stratification and, in select cases, helps select targeted therapies.
- |||||||||| Revlimid (lenalidomide) / BMS
Clinical, Review, Journal: Current Therapy of the Patients with MDS: Walking towards Personalized Therapy. (Pubmed Central) - Jun 3, 2021
Additionally, luspatercept has recently been added to treat patients with MDS with ring sideroblasts, who are not candidates or have lost the response to erythropoiesis-stimulating agents...In recent years, we are witnessing the emergence of multiple treatment combinations based on hypomethylating agents (pevonedistat, magrolimab, eprenetapopt, venetoclax) that have proven to be effective in MDS, even those with high-risk factors...Relapsed and refractory patients remain an unmet clinical need. We need more drugs and clinical trials for this profile of patients who have a dismal prognosis.
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Journal: Development of luspatercept to treat ineffective erythropoiesis. (Pubmed Central) - Jun 1, 2021
Especially in the subgroup of MDS patients with RS, luspatercept showed high clinical activity for the treatment of anemia in the phase 2 (PACE-MDS) trial and subsequently in the phase 3 (MEDALIST) trial, which resulted in approval by both the US Food and Drug Administration and the European Medicines Agency in April 2020. Additional studies are needed to better understand the mechanism of action and pharmacodynamics of this novel agent in MDS.
- |||||||||| [VIRTUAL] Potential New Therapeutic Approaches for Myelofibrosis () - May 20, 2021 - Abstract #SOHO2021SOHO_158;
Targeting the p53-HDM2 Axis KRT-232 is a first-in-class, potent, bioavailable inhibitor of HDM2 (key negative regulator of p53) that was assessed in a phase 2 study (KRT-232-101) and showed promising clinical efficacy and tolerability in TP53-wild type patients with MF who failed ruxolitinib treatment.17 A randomized phase 3 trial comparing KRT-232 (240 mg on days 1–7/28-day cycle) to BAT in MF patients refractory /resistant to JAK inhibitors has been launched...In the phase 2 study IMbark, the higher dose of imetelstat (9.4 mg/ kg) yielded a median overall survival of 29.9 months in patients with intermediate-2 or high-risk MF relapsed/refractory to JAK inhibitors.18 In light of the aforementioned promising result, a pivotal international phase 3 trial (IMpactMF) was launched to evaluate the survival advantage – an unprecedented trial endpoint for investigational MF medications – that imetelstat may confer to JAK-inhibitor-refractory MF patients.19 Conclusions The era of JAK1/2 inhibitor monotherapies in MF has ushered the way to the clinical development of a suite of promising novel medications spanning various biological mechanisms (for example, inhibitors of BET, HDM2, BCL-2/ BCL-XL, and telomerase, among others). Several highly promising candidates are currently evaluated in regulatory phase 3 clinical trials in the frontline and second line settings; these studies may lead to approval of novel medications that will significantly improve the current MF treatment paradigm.
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
Clinical, Journal: The use of luspatercept for thalassemia in adults. (Pubmed Central) - May 15, 2021
P2, P3
Luspatercept was approved by the US Food and Drug Administration in 2019 and by the European Medicines Agency in 2020. The luspatercept trial is registered on www.clinicaltrials.gov at #NCT01749540 and the BELIEVE trial at #NCT02604433.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] TFR2-HAPLOINSUFFICIENCY IMPROVES THE PHENOTYPE IN A MURINE MODEL OF TRANSFUSION-DEPENDENT Β-THALASSEMIA () - May 13, 2021 - Abstract #EHA2021EHA_2062;
Other recently approved treatments (i.e. gene therapy and luspatercept), despite promising, are only partially effective and/or suitable for selected patients...Conclusion Overall our data show that Tfr2 targeting might represent a valuable therapeutic option for the most severe form of β-thalassemia, ameliorating several features of the disease. However, the effect of full BM Tfr2 inactivation, that we expect more efficient in correcting anemia and ineffective erythropoiesis, and the potential role of Tfr2 deletion in the reduction of blood transfusion requirement, the standard treatment for TDT but correlated to several complications, remain to be evaluated.
- |||||||||| Zarzio (filgrastim biosimilar) / Novartis
[VIRTUAL] MUTATIONAL ANALYSIS IN LOW RISK MYELODYSPLASTIC SYNDROMES: A SINGLE CENTER REPORT () - May 13, 2021 - Abstract #EHA2021EHA_1637;
Recently, a deeper knowledge of LR MDS molecular landscape paved the way to novel treatments, such as luspatercept for SF3B1 mutated patients with ring sideroblasts...Considering mutation types, expectedly, those involving splicing pathway correlated with a more proliferative phenotype. Interestingly, somatic mutations did not negatively impact on response to recombinant erythropoietin
- |||||||||| [VIRTUAL] A PHASE 3 STUDY OF THE EFFICACY AND SAFETY OF LUSPATERCEPT VERSUS EPOETIN ALFA FOR THE TREATMENT OF ANEMIA DUE TO LOWER-RISK MDS IN ESA-NAIVE PATIENTS REQUIRING RBC TRANSFUSIONS (THE COMMANDS TRIAL) () - May 13, 2021 - Abstract #EHA2021EHA_1636;
P3
Epoetin alfa and darbepoetin alfa have shown efficacy among pts with LR-MDS, but the pt population in whom a clinically significant effect is seen may be limited...Exclusion criteria include prior use of ESAs (≤2 doses of prior epoetin alfa permitted if ≥8 weeks from randomization date and sEPO confirmed as ≤ 500 U/L), granulocyte colony-stimulating factor or granulocyte-macrophage colony-stimulating factor, unless administered for treatment of febrile neutropenia; disease-modifying agents (e.g. lenalidomide), or hypomethylating agents; and presence of del(5q) cytogenetic abnormality...Key secondary endpoints include duration of RBC-TI, change in Hb levels, achievement of HI-E (per International Working Group [IWG] 2006), and safety. Conclusion The COMMANDS trial is registered at EudraCT (number 2017-003190-34) and ClinicalTrials.gov (NCT03682536).
- |||||||||| Reblozyl (luspatercept-aamt) / Acceleron, BMS
[VIRTUAL] BENEFIT OF CONTINUING LUSPATERCEPT THERAPY IN PATIENTS WITH LOWER-RISK MYELODYSPLASTIC SYNDROMES WHO DID NOT ACHIEVE RED BLOOD CELL TRANSFUSION INDEPENDENCE BY WEEK 25 IN THE MEDALIST STUDY () - May 13, 2021 - Abstract #EHA2021EHA_1615;
P3
Over the entire treatment period up to the data cutoff, 60.3% (n=41/68) achieved ≥50% reduction in transfusion burden for ≥8 weeks from baseline, 22.1% (n=15/68) achieved RBC-TI for ≥8 weeks, and 48.5% (n=33/68) achieved HI-E response. Conclusion A considerable proportion of patients with LR-MDS in the MEDALIST study who did not achieve the primary endpoint, but continued to receive luspatercept beyond 24 weeks of treatment, experienced a broad range of clinical improvements, including reduced transfusion burden, reduced SF levels, and even TI.
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