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Blood Advances Mar 2021Azacitidine + venetoclax, decitabine + venetoclax, and low-dose cytarabine + venetoclax are now standard treatments for newly diagnosed older or unfit patients with...
Azacitidine + venetoclax, decitabine + venetoclax, and low-dose cytarabine + venetoclax are now standard treatments for newly diagnosed older or unfit patients with acute myeloid leukemia (AML). Although these combinations are also commonly used in relapsed or refractory AML (RR-AML), clinical and molecular predictors of response and survival in RR-AML are incompletely understood. We retrospectively analyzed clinical and molecular characteristics and outcomes for 86 patients with RR-AML who were treated with venetoclax combinations. The complete remission (CR) or CR with incomplete hematologic recovery (CRi) rate was 24%, and the overall response rate was 31% with the inclusion of a morphologic leukemia-free state. Azacitidine + venetoclax resulted in higher response rates compared with low-dose cytarabine + venetoclax (49% vs 15%; P = .008). Median overall survival (OS) was 6.1 months, but it was significantly longer with azacitidine + venetoclax compared with low-dose cytarabine + venetoclax (25 vs 3.9 months; P = .003). This survival advantage of azacitidine + venetoclax over low-dose cytarabine + venetoclax persisted when patients were censored for subsequent allogeneic stem cell transplantation (8.1 vs 3.9 months; P = .035). Mutations in NPM1 were associated with higher response rates, whereas adverse cytogenetics and mutations in TP53, KRAS/NRAS, and SF3B1 were associated with worse OS. Relapse was driven by diverse mechanisms, including acquisition of novel mutations and an increase in cytogenetic complexity. Venetoclax combination therapy is effective in many patients with RR-AML, and pretreatment molecular characteristics may predict outcomes. Trials that evaluate novel agents in combination with venetoclax therapy in patients with RR-AML that have adverse risk genomic features are warranted.
Topics: Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Decitabine; Humans; Leukemia, Myeloid, Acute; Nucleophosmin; Retrospective Studies; Sulfonamides
PubMed: 33687434
DOI: 10.1182/bloodadvances.2020003734 -
The Journal of Clinical Investigation Apr 2023CD8+ exhausted T cells (Tex) are heterogeneous. PD-1 inhibitors reinvigorate progenitor Tex, which subsequently differentiate into irresponsive terminal Tex. The ability...
CD8+ exhausted T cells (Tex) are heterogeneous. PD-1 inhibitors reinvigorate progenitor Tex, which subsequently differentiate into irresponsive terminal Tex. The ability to maintain a capacity for durable proliferation of progenitor Tex is important, but the mechanism remains unclear. Here, we showed CD8+ progenitor Tex pretreated with decitabine, a low-dose DNA demethylating agent, had enhanced proliferation and effector function against tumors after anti-PD-1 treatment in vitro. Treatment with decitabine plus anti-PD-1 promoted the activation and expansion of tumor-infiltrated CD8+ progenitor Tex and efficiently suppressed tumor growth in multiple tumor models. Transcriptional and epigenetic profiling of tumor-infiltrated T cells demonstrated that the combination of decitabine plus anti-PD-1 markedly elevated the clonal expansion and cytolytic activity of progenitor Tex compared with anti-PD-1 monotherapy and restrained CD8+ T cell terminal differentiation. Strikingly, decitabine plus anti-PD-1 sustained the expression and activity of the AP-1 transcription factor JunD, which was reduced following PD-1 blockade therapy. Downregulation of JunD repressed T cell proliferation, and activation of JNK/AP-1 signaling in CD8+ T cells enhanced the antitumor capacity of PD-1 inhibitors. Together, epigenetic agents remodel CD8+ progenitor Tex populations and improve responsiveness to anti-PD-1 therapy.
Topics: Humans; Decitabine; Immune Checkpoint Inhibitors; Transcription Factor AP-1; CD8-Positive T-Lymphocytes; Neoplasms; Cell Proliferation
PubMed: 36853831
DOI: 10.1172/JCI165673 -
Science Translational Medicine Aug 2023Aging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS). Here, we demonstrated that persistent lung injury...
Aging is a major risk factor of high incidence and increased mortality of acute respiratory distress syndrome (ARDS). Here, we demonstrated that persistent lung injury and high mortality in aged mice after sepsis challenge were attributable to impaired endothelial regeneration and vascular repair. Genetic lineage tracing study showed that endothelial regeneration after sepsis-induced vascular injury was mediated by lung resident endothelial proliferation in young adult mice, whereas this intrinsic regenerative program was impaired in aged mice. Expression of forkhead box M1 (FoxM1), an important mediator of endothelial regeneration in young mice, was not induced in lungs of aged mice. Transgenic expression or in vivo endothelium-targeted nanoparticle delivery of the gene driven by an endothelial cell (EC)-specific promoter reactivated endothelial regeneration, normalized vascular repair and resolution of inflammation, and promoted survival in aged mice after sepsis challenge. In addition, treatment with the FDA-approved DNA demethylating agent decitabine was sufficient to reactivate FoxM1-dependent endothelial regeneration in aged mice, reverse aging-impaired resolution of inflammatory injury, and promote survival. Mechanistically, aging-induced promoter hypermethylation in mice, which could be inhibited by decitabine treatment, inhibited induction after sepsis challenge. In COVID-19 lung autopsy samples, was not induced in vascular ECs of elderly patients in their 80s, in contrast with middle-aged patients (aged 50 to 60 years). Thus, reactivation of FoxM1-mediated endothelial regeneration and vascular repair may represent a potential therapy for elderly patients with ARDS.
Topics: Animals; Mice; COVID-19; Decitabine; Endothelium, Vascular; Forkhead Box Protein M1; Lung; Lung Injury; Mice, Transgenic; Regeneration; Respiratory Distress Syndrome; Sepsis
PubMed: 37585502
DOI: 10.1126/scitranslmed.abm5755 -
Blood Apr 2023
Topics: Ipilimumab; Decitabine
PubMed: 37052941
DOI: 10.1182/blood.2023019739 -
The Lancet. Haematology Nov 2023Many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive... (Randomized Controlled Trial)
Randomized Controlled Trial
10-day decitabine versus 3 + 7 chemotherapy followed by allografting in older patients with acute myeloid leukaemia: an open-label, randomised, controlled, phase 3 trial.
BACKGROUND
Many older patients with acute myeloid leukaemia die or cannot undergo allogeneic haematopoietic stem-cell transplantation (HSCT) due to toxicity caused by intensive chemotherapy. We hypothesised that replacing intensive chemotherapy with decitabine monotherapy could improve outcomes.
METHODS
This open-label, randomised, controlled, phase 3 trial was conducted at 54 hospitals in nine European countries. Patients aged 60 years and older who were newly diagnosed with acute myeloid leukaemia and had not yet been treated were enrolled if they had an Eastern Cooperative Oncology Group performance status of 2 or less and were eligible for intensive chemotherapy. Patients were randomly assigned (1:1) to receive decitabine or standard chemotherapy (known as 3 + 7). For the decitabine group, decitabine (20 mg/m) was administered for the first 10 days in the first 28-day cycle, followed by 28-day cycles consisting of 5 days or 10 days of decitabine. For the 3 + 7 group, daunorubicin (60 mg/m) was administered over the first 3 days and cytarabine (200 mg/m) over the first 7 days, followed by 1-3 additional chemotherapy cycles. Allogeneic HSCT was strongly encouraged. Overall survival in the intention-to-treat population was the primary endpoint. Safety was assessed in all patients who received the allocated treatment. This trial is registered at ClinicalTrials.gov, NCT02172872, and is closed to new participants.
FINDINGS
Between Dec 1, 2014, and Aug 20, 2019, 606 patients were randomly assigned to the decitabine (n=303) or 3 + 7 (n=303) group. Following an interim analysis which showed futility, the IDMC recommended on May 22, 2019, that the study continued as planned considering the risks and benefits for the patients participating in the study. The cutoff date for the final analysis presented here was June 30, 2021. At a median follow-up of 4·0 years (IQR 2·9-4·8), 4-year overall survival was 26% (95% CI 21-32) in the decitabine group versus 30% (24-35) in the 3 + 7 group (hazard ratio for death 1·04 [95% CI 0·86-1·26]; p=0·68). Rates of on-protocol allogeneic HSCT were similar between groups (122 [40%] of 303 patients for decitabine and 118 [39%] of 303 patients for 3+7). Rates of grade 3-5 adverse events were 254 (84%) of 302 patients in the decitabine group and 279 (94%) of 298 patients in the 3 + 7 group. The rates of grade 3-5 infections (41% [125 of 302] vs 53% [158 of 298]), oral mucositis (2% [seven of 302] vs 10% [31 of 298]) and diarrhoea (1% [three of 302] vs 8% [24 of 298]) were lower in the decitabine group than in the 3 + 7 group. Treatment-related deaths were reported for 12% (35 of 302) of patients in the decitabine group and 14% (41 of 298) in the 3 + 7 group.
INTERPRETATION
10-day decitabine did not improve overall survival but showed a better safety profile compared with 3 + 7 chemotherapy in older patients with acute myeloid leukaemia eligible for intensive chemotherapy. Decitabine could be considered a better-tolerated and sufficiently efficacious alternative to 3 + 7 induction in fit older patients with acute myeloid leukaemia without favourable genetics.
FUNDING
Janssen Pharmaceuticals.
Topics: Humans; Middle Aged; Aged; Decitabine; Leukemia, Myeloid, Acute; Cytarabine; Daunorubicin; Transplantation, Homologous; Antineoplastic Combined Chemotherapy Protocols
PubMed: 37914482
DOI: 10.1016/S2352-3026(23)00273-9 -
American Journal of Health-system... Oct 2020
Topics: Administration, Oral; Adult; Antineoplastic Agents; Cytidine Deaminase; DNA Methylation; DNA Modification Methylases; Decitabine; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Combinations; Drug Interactions; Drug Labeling; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Myelodysplastic Syndromes; Uridine
PubMed: 32945859
DOI: 10.1093/ajhp/zxaa276 -
The Lancet. Haematology Oct 2020Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukaemia (AML) who are 75 years or older, or...
10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial.
BACKGROUND
Venetoclax combined with hypomethylating agents is a new standard of care for newly diagnosed patients with acute myeloid leukaemia (AML) who are 75 years or older, or unfit for intensive chemotherapy. Pharmacodynamic studies have suggested superiority of the longer 10-day regimen of decitabine that has shown promising results in patients with high-risk AML in phase 2 trials. We hypothesised that venetoclax with 10-day decitabine could have improved activity in patients with newly diagnosed AML and those with relapsed or refractory AML, particularly in high-risk subgroups.
METHODS
This single centre, phase 2 trial was done at the University of Texas MD Anderson Cancer Center (Houston, TX, USA). The study enrolled older patients (aged >60 years) with newly diagnosed AML, not eligible for intensive chemotherapy; secondary AML (progressed after myelodysplastic syndrome or chronic myelomonocytic leukaemia); and relapsed or refractory AML. Patients were required to have an Eastern Cooperative Oncology Group (ECOG) performance status of 3 or less, white blood cell count less than 10 × 10 per L, and adequate end-organ function. Patients with favourable-risk cytogenetics (eg, t[15;17] or core-binding factor AML) or who had received previous BCL2-inhibitor therapy were excluded. Patients received decitabine 20 mg/m intravenously for 10 days with oral venetoclax 400 mg daily for induction, followed by decitabine for 5 days with daily venetoclax for consolidation. The primary endpoint was overall response rate. The secondary endpoints analysed within this report include safety, overall survival, and duration of response, in keeping with recommendations of European LeukemiaNet 2017 guidelines. All patients who received at least one dose of treatment were eligible for safety and response assessments. The trial was registered on ClinicalTrials.gov (NCT03404193) and continues to accrue patients.
FINDINGS
Between Jan 19, 2018, and Dec 16, 2019, we enrolled 168 patients; 70 (42%) had newly diagnosed AML, 15 (9%) had untreated secondary AML, 28 (17%) had treated secondary AML, and 55 (33%) had relapsed or refractory AML. The median age was 71 years (IQR 65-76) and 30% of patients had ECOG performance status of 2 or higher. The median follow-up for all patients was 16 months (95% CI 12-18; actual follow-up 6·5 months; IQR 3·4-12·4). The overall response rate was 74% (125 of 168 patients; 95% CI 67-80) and in disease subgroups were: 89% in newly diagnosed AML (62 of 70 patients; 79-94), 80% in untreated secondary AML (12 of 15 patients; 55-93), 61% in treated secondary AML (17 of 28 patients; 42-76), and 62% in relapsed or refractory AML (34 of 55 patients; 49-74). The most common treatment-emergent adverse events included infections with grades 3 or 4 neutropenia (n=79, 47%) and febrile neutropenia (n=49, 29%). 139 (83%) of 168 patients had serious adverse events, most frequently neutropenic fever (n=63, 38%), followed by pneumonia (n=17, 10%) and sepsis (n=16, 10%). The 30-day mortality for all patients was 3·6% (n=6, 95% CI 1·7-7·8). The median overall survival was 18·1 months (95% CI 10·0-not reached) in newly diagnosed AML, 7·8 months (2·9-10·7) in untreated secondary AML, 6·0 months (3·4-13·7) in treated secondary AML, and 7·8 months (5·4-13·3) relapsed or refractory AML. The median duration of response was not reached (95% CI 9·0-not reached) in newly diagnosed AML, 5·1 months (95% CI 0·9-not reached) in untreated secondary AML, not reached (95% CI 2·5-not reached) in previously treated secondary AML, and 16·8 months (95% CI 6·6-not reached) in relapsed or refractory AML.
INTERPRETATION
Venetoclax with 10-day decitabine has a manageable safety profile and showed high activity in newly diagnosed AML and molecularly defined subsets of relapsed or refractory AML. Future larger and randomised studies are needed to clarify activity in high-risk subsets.
FUNDING
US National Institutes of Health and National Cancer Institute.
Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bridged Bicyclo Compounds, Heterocyclic; Decitabine; Drug Administration Schedule; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Neoplasm Recurrence, Local; Sulfonamides; Treatment Outcome
PubMed: 32896301
DOI: 10.1016/S2352-3026(20)30210-6 -
Science Translational Medicine Nov 2023Aberrant DNA methylation has been implicated as a key driver of prostate cancer lineage plasticity and histologic transformation to neuroendocrine prostate cancer...
Aberrant DNA methylation has been implicated as a key driver of prostate cancer lineage plasticity and histologic transformation to neuroendocrine prostate cancer (NEPC). DNA methyltransferases (DNMTs) are highly expressed, and global DNA methylation is dysregulated in NEPC. We identified that deletion of DNMT genes decreases expression of neuroendocrine lineage markers and substantially reduced NEPC tumor development and metastasis in vivo. Decitabine, a pan-DNMT inhibitor, attenuated tumor growth in NEPC patient-derived xenograft models, as well as retinoblastoma gene ()-deficient castration-resistant prostate adenocarcinoma (CRPC) models compared with -proficient CRPC. We further found that DNMT inhibition increased expression of B7 homolog 3 (B7-H3), an emerging druggable target, via demethylation of B7-H3. We tested DS-7300a (i-DXd), an antibody-drug conjugate targeting B7-H3, alone and in combination with decitabine in models of advanced prostate cancer. There was potent single-agent antitumor activity of DS-7300a in both CRPC and NEPC bearing high expression of B7-H3. In B7-H3-low models, combination therapy of decitabine plus DS-7300a resulted in enhanced response. DNMT inhibition may therefore be a promising therapeutic target for NEPC and RB1-deficient CRPC and may sensitize B7-H3-low prostate cancer to DS-7300a through increasing target expression. NEPC and RB1-deficient CRPC represent prostate cancer subgroups with poor prognosis, and the development of biomarker-driven therapeutic strategies for these populations may ultimately help improve patient outcomes.
Topics: Male; Humans; Prostatic Neoplasms, Castration-Resistant; DNA Methylation; Decitabine; Cell Line, Tumor; Prostatic Neoplasms; Neuroendocrine Tumors; Transcription Factors; Antineoplastic Agents; Ubiquitin-Protein Ligases; Retinoblastoma Binding Proteins
PubMed: 37967200
DOI: 10.1126/scitranslmed.adf6732 -
The Lancet. Oncology Feb 2018Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating... (Comparative Study)
Comparative Study
Safety and preliminary efficacy of venetoclax with decitabine or azacitidine in elderly patients with previously untreated acute myeloid leukaemia: a non-randomised, open-label, phase 1b study.
BACKGROUND
Elderly patients (aged ≥65 years) with acute myeloid leukaemia have poor outcomes and no effective standard-of-care therapy exists. Treatment with hypomethylating agents such as azacitidine and decitabine is common, but responses are modest and typically short-lived. The oral anti-apoptotic B-cell lymphoma 2 protein inhibitor, venetoclax, has shown promising single-agent activity in patients with relapsed or refractory acute myeloid leukaemia and preclinical data suggested synergy between hypomethylating agents and venetoclax, which led to this combination phase 1b study.
METHODS
Previously untreated patients aged 65 years and over with acute myeloid leukaemia who were ineligible for standard induction therapy were enrolled into this non-randomised, open-label, phase 1b study. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0-2 and either intermediate-risk or poor-risk cytogenetics. Patients were enrolled into one of three groups for the dose-escalation phase of this study: group A (venetoclax and intravenous decitabine 20 mg/m [days 1-5 of each 28-day cycle]), group B (venetoclax and subcutaneous or intravenous azacitidine 75 mg/m [days 1-7 of each 28-day cycle]), and group C (a venetoclax and decitabine substudy with the oral CYP3A inhibitor posaconazole, 300 mg twice on cycle 1, day 21, and 300 mg once daily from cycle 1, days 22-28, to assess its effect on venetoclax pharmacokinetics). Dose escalation followed a standard 3 + 3 design with at least three evaluable patients enrolled per cohort; daily target doses of venetoclax for groups A and B were 400 mg (cohort 1), 800 mg (cohorts 2 and 3), and 1200 mg (cohort 4), and 400 mg for group C. The primary endpoints were the safety and pharmacokinetics of venetoclax plus decitabine or azacitidine, and to determine the maximum tolerated dose and recommended phase 2 dose. Secondary endpoints included the preliminary anti-leukaemic activity of venetoclax with decitabine or azacitidine through the analysis of overall response, duration of response, and overall survival. We analysed safety, pharmacokinetics, and anti-leukaemic activity in all patients who received one or more venetoclax doses. The expansion phase of the study is ongoing but is closed to accrual. This trial is registered with ClinicalTrials.gov, number NCT02203773.
FINDINGS
57 patients were enrolled in the study. 23 patients in group A and 22 patients in group B were enrolled between Nov 19, 2014, and Dec 15, 2015, and 12 patients in group C were enrolled between June 14, 2015, and Jan 16, 2016. As of data cutoff on June 15, 2016, the most common grade 3-4 treatment-emergent adverse events were thrombocytopenia (27 [47%] of 57 patients; nine in group A, 13 in group B, and five in group C), febrile neutropenia (24 [42%] of 57; 11 in group A, ten in group B, and three in group C), and neutropenia (23 [40%] of 57; 12 in group A, eight in group B, and three in group C). The most common serious treatment-emergent adverse event in groups A and B was febrile neutropenia (seven [30%] of 23 patients vs seven [32%] of 22), whereas in group C it was lung infection (four [33%] of 12 patients). 49 (86%) of 57 patients had treatment-related adverse events; the most common in groups A and B included nausea (12 [52%] patients vs seven [32%] patients), fatigue (six [26%] patients vs seven [32%]), and decreased neutrophil count (six [26%] patients vs six [27%]), whereas in group C the most common were nausea (seven [58%] of 12 patients), leucopenia (six [50%]), vomiting (five [42%]), and decreased platelet count (five [42%]). The maximum tolerated dose was not reached. The recommended phase 2 dose was 400 mg once a day or 800 mg with an interrupted dosing schedule (safety expansion). In total, four (7%) of 57 patients had died within 30 days of the first venetoclax dose caused by sepsis (group B), bacteraemia (group A), lung infection (group C), and respiratory failure (group A). Tumour lysis syndrome was not observed. Decitabine and azacitidine did not substantially affect venetoclax exposures. Overall, 35 (61%; 95% CI 47·6-74·0) of 57 patients achieved complete remission or complete remission with incomplete marrow recovery. In groups A and B, 27 (60%; 95% CI 44·3-74·3) of 45 patients had complete remission or complete remission with incomplete marrow recovery.
INTERPRETATION
Venetoclax plus hypomethylating agent therapy seems to be a novel, well-tolerated regimen with promising activity in this underserved patient population. Evaluation of expansion cohorts is ongoing at 400 mg and 800 mg doses using both hypomethylating agent combinations.
FUNDING
AbbVie and Genentech.
Topics: Administration, Oral; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Azacitidine; Bridged Bicyclo Compounds, Heterocyclic; Confidence Intervals; Decitabine; Disease-Free Survival; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Geriatric Assessment; Humans; Infusions, Intravenous; Kaplan-Meier Estimate; Leukemia, Myeloid, Acute; Male; Maximum Tolerated Dose; Patient Safety; Prognosis; Remission Induction; Sulfonamides; Survival Analysis; Treatment Outcome
PubMed: 29339097
DOI: 10.1016/S1470-2045(18)30010-X -
Journal of Oncology Pharmacy Practice :... Dec 2021There have been several advances in the field of myelodysplastic syndromes over the past year, yielding two new US Food and Drug Administration drug approvals. The... (Review)
Review
REVIEW OBJECTIVE
There have been several advances in the field of myelodysplastic syndromes over the past year, yielding two new US Food and Drug Administration drug approvals. The pharmacology, pharmacokinetics, clinical trials, therapeutic use, adverse effects, clinical use controversies, product description, and upcoming trials for myelodysplastic syndromes novel agents luspatercept-aamt and decitabine/cedazuridine are reviewed.
DATA SOURCES
This review article utilized primary information obtained from both the published studies involved in the approval of luspatercept-aamt and decitabine/cedazuridine and package inserts for the respective medications. This review article utilized secondary information obtained from National Comprehensive Cancer Network guidelines using filters and keywords to sustain information relevancy as well as key studies using the keywords, "luspatercept-aamt, myelodysplastic syndromes, decitabine, cedazuridine, hypomethylating agent, ASTX727" from scholarly journal database PubMed.
DATA SUMMARY
Myelodysplastic syndromes consist of myeloid clonal hemopathies with a diverse range of presentation. Until recently, there have been relatively few new therapies in the myelodysplastic syndromes treatment landscape. On April 3, 2020 the US Food and Drug Administration approved Reblozyl(luspatercept-aamt), then on July 7, 2020, the US Food and Drug Administration approved INQOVI (decitabine and cedazuridine). Luspatercept-aamt acts as a erythroid maturation agent through differentiation of late-stage erythroid precursors. The safety and efficacy of luspatercept-aamt was demonstrated in the MEDALIST trial, a phase III trial in patients with very low-intermediate risk refractory myelodysplastic syndromes and ring sideroblasts. Luspatercept-aamt met both primary and secondary endpoints of transfusion independence of 8 weeks or longer and transfusion independence of 12 weeks or longer, respectively. Decitabine/cedazuridine has a unique mechanism of action in which decitabine acts as a nucleoside metabolic inhibitor promoting DNA hypomethylation and cedazuridine then prevents degradation of decitabine. The safety and efficacy of decitabine/cedazuridine was shown in the ASCERTAIN study, a phase III trial in patients with intermediate or high risk myelodysplastic syndromes or chronic myelomonocytic leukemia. The primary outcome evaluated was 5-day cumulative area under the curve between decitabine/cedazuridine and IV decitabine as well as additional outcomes including safety. Decitabine/cedazuridine met primary outcome and had a similar safety profile to IV decitabine.
CONCLUSION
The novel myelodysplastic syndromes agents luspatercept-aamt and decitabine/cedazuridine provide a clinical benefit in the studied populations.
Topics: Azacitidine; Decitabine; Drug Approval; Humans; Leukemia, Myelomonocytic, Chronic; Myelodysplastic Syndromes; United States; United States Food and Drug Administration
PubMed: 34558354
DOI: 10.1177/10781552211037993