scholarly journals What to use to treat AML: the role of emerging therapies

Hematology ◽  
2021 ◽  
Vol 2021 (1) ◽  
pp. 16-23
Author(s):  
Felicitas Thol
Keyword(s):  
Older Adult ◽  
Treatment Options ◽  
Intensive Therapy ◽  
Standard Of Care ◽  
Gemtuzumab Ozogamicin ◽  
European Medicines Agency ◽  
Molecular Testing ◽  
Newly Diagnosed ◽  
Antibody Drug Conjugate ◽  
Isocitrate Dehydrogenase 1

Abstract The development and approval of novel substances have resulted in substantial improvements in the treatment of acute myeloid leukemia (AML). In the current era of novel treatment options, genetic and molecular testing at the time of diagnosis and relapse becomes increasingly relevant. Midostaurin in combination with intensive chemotherapy is the standard of care as upfront therapy in younger AML patients with mutated fms-related tyrosine kinase 3 (FLT3). Gilteritinib, a second- generation FLT3 inhibitor, represents a key drug for relapsed/refractory (R/R) FLT3-mutated AML patients. Targeted therapy has also been developed for patients with mutated isocitrate dehydrogenase 1 (IDH1) and IDH2. The US Food and Drug Administration (FDA) approved ivosidenib as a monotherapy for newly diagnosed older adult IDH1-mutated patients and enasidenib for R/R IDH2-mutated AML patients. CPX-351, a liposomal formulation of daunorubicin and cytarabine, has become an important upfront treatment strategy for fit patients with therapy-related AML or AML with myelodysplasia-related changes that are generally challenging to treat. The antibody drug conjugate gemtuzumab ozogamicin was approved in combination with intensive therapy for patients with newly diagnosed (FDA/European Medicines Agency [EMA]) as well as R/R CD33+ AML. The combination of venetoclax, an oral selective B-cell leukemia/lymphoma-2 inhibitor, with hypomethylating agents or low-dose AraC (LDAC) has changed the treatment landscape and prognosis for older adult patients very favorably. The addition of glasdegib, a small-molecule hedgehog inhibitor, to LDAC is another example of novel options in older patients. Further substances have shown promising results in early clinical trials.

scholarly journals Intermediate-risk acute myeloid leukemia therapy: current and future

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 34-43 ◽  
Author(s):  
Konstanze Döhner ◽  
Peter Paschka
Keyword(s):  
Acute Myeloid Leukemia ◽  
Myeloid Leukemia ◽  
Intensive Therapy ◽  
Standard Of Care ◽  
Gemtuzumab Ozogamicin ◽  
High Dose ◽  
Genetic Profile ◽  
Molecular Heterogeneity ◽  
Intermediate Risk ◽  
Acute Myeloid

Abstract In recent years, research in molecular genetics has been instrumental in deciphering the molecular heterogeneity of acute myeloid leukemia (AML), in particular the subset of patients with “intermediate-risk” cytogenetics. However, at present, only the markers NPM1, CEBPA, and FLT3 have entered clinical practice. Treatment of intermediate-risk AML patients eligible for intensive therapy has not changed substantially. The “3 + 7” induction therapy still represents the standard of care. The addition of the immunoconjugate gemtuzumab ozogamicin to therapy has been shown to improve outcome; however, the drug is not approved for this use. A common standard for postremission therapy is the administration of repeated cycles of intermediate- to high-dose cytarabine. Allogeneic stem cell transplantation may offer a survival benefit for many patients with intermediate-risk AML. Patients are best selected based on the genetic profile of the leukemia cells and the risk associated with the transplantation itself. A myriad of novel agents targeting mutant leukemia drivers or deregulated pathways are in clinical development. In the past, many novel compounds have not met expectations; nonetheless, with the rapid developments in comprehensive molecular profiling and new drug design, there is the prospect of personalizing therapy and improving patient outcome.

scholarly journals Biliary Tract Cancers: Molecular Heterogeneity and New Treatment Options

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3370
Author(s):  
Nicola Personeni ◽  
Ana Lleo ◽  
Tiziana Pressiani ◽  
Francesca Colapietro ◽  
Mark Robert Openshaw ◽  
...  
Keyword(s):  
Biliary Tract ◽  
Advanced Disease ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Resistance Mechanisms ◽  
Anatomical Location ◽  
Molecular Heterogeneity ◽  
Isocitrate Dehydrogenase 1 ◽  
Tract Cancer

Most patients with biliary tract cancer (BTC) are diagnosed with advanced disease, relapse rates are high in those undergoing surgery and prognosis remains poor, while the incidence is increasing. Treatment options are limited, and chemotherapy is still the standard of care in both adjuvant and advanced disease setting. In recent years, different subtypes of BTC have been defined depending on the anatomical location and genetic and/or epigenetic aberrations. Especially for intrahepatic cholangiocarcinoma (iCCA) novel therapeutic targets have been identified, including fibroblast growth factor receptor 2 gene fusions and isocitrate dehydrogenase 1 and 2 mutations, with molecularly targeted agents having shown evidence of activity in this subgroup of patients. Additionally, other pathways are being evaluated in both iCCA and other subtypes of BTC, alongside targeting of the immune microenvironment. The growing knowledge of BTC biology and molecular heterogeneity has paved the way for the development of new therapeutic approaches that will completely change the treatment paradigm for this disease in the near future. This review provides an overview of the molecular heterogeneity of BTC and summarizes new targets and emerging therapies in development. We also discuss resistance mechanisms, open issues, and future perspectives in the management of BTC.

scholarly journals Gemtuzumab ozogamicin for acute myeloid leukemia

Blood ◽  
2017 ◽  
Vol 130 (22) ◽  
pp. 2373-2376 ◽  
Author(s):  
Frederick R. Appelbaum ◽  
Irwin D. Bernstein
Keyword(s):  
Acute Myeloid Leukemia ◽  
Initial Treatment ◽  
Myeloid Leukemia ◽  
Gemtuzumab Ozogamicin ◽  
Newly Diagnosed ◽  
Antibody Drug Conjugate ◽  
The Us ◽  
Human Use ◽  
Acute Myeloid ◽  
Antibody Drug

Abstract On 1 September 2017, the US Food and Drug Administration (FDA) approved gemtuzumab ozogamicin (GO) for the treatment of adults with newly diagnosed CD33+ acute myeloid leukemia and for patients aged ≥2 years with CD33+ acute myeloid leukemia who have experienced a relapse or who have not responded to initial treatment. This signals a new chapter in the long and unusual story of GO, which was the first antibody–drug conjugate approved for human use by the FDA.

Non-small cell lung cancer (NSCLC) next generation sequencing (NGS) using the Oncomine Comprehensive Assay (OCA) v3: Integrating expanded genomic sequencing into the Canadian publicly funded health care model.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2620-2620
Author(s):  
Kirstin Perdrizet ◽  
Tracy Stockley ◽  
Jennifer H. Law ◽  
Muqdas Shabir ◽  
Tong Zhang ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Treatment Options ◽  
Stage Iv ◽  
Standard Of Care ◽  
Copy Number Variations ◽  
Public Healthcare ◽  
Molecular Testing ◽  
Publicly Funded ◽  
A Prospective Study ◽  
Nsclc Patients

2620 Background: Standard of care (SOC) molecular diagnostics for stage IV NSCLC patients in Ontario, Canada includes publicly reimbursed EGFR/ ALK, and selected BRAF and ROS-1 testing. Other genomic alterations are not tested routinely; however, enhanced molecular testing may broaden treatment options for patients. This study evaluated costs, identified actionable targets, and determined clinical trial eligibility as a result of using the OCAv3 NGS in stage IV NSCLC patients. Methods: In a prospective study of stage IV NSCLC out-patients at Princess Margaret Cancer Centre (Toronto) without EGFR/ALK/KRAS/BRAF alteration (unless failure of prior targeted therapy), diagnostic samples were tested by OCAv3 (ThermoFisher; 161 genes: hotspots, fusions, and copy number variations). Primary endpoints were incremental actionable targets and clinical trial opportunities as a result of broader OCAv3 testing. Secondary endpoints include feasibility and cost from the Canadian public healthcare perspective, and treatment outcomes. Results: Of 65 enrolled patients (Feb 2018-Jan 2019; 40 (62%) completed/14 (21%) screen fail/ 11 (17%) pending), median age of completed cohort was 65, 60% (N = 24) female, never/light smokers 68% (N = 27), Asian 38% (N = 15), previously treated 33% (N = 13). Actionable targets beyond SOC were identified in 33% (N = 13): ERBB2 (N = 8), BRAFV600 (N = 3), NRG fusion (N = 1), MET exon 14 (N = 1). New clinical trial options were identified in 70%. Failure of NGS was secondary to insufficient tissue [91% (N = 10) of screen failures; usually due to tissue exhaustion from prior SOC molecular testing]. Incremental costs per case beyond EGFR/ALK are estimated at $540 CAD. If ROS-1 and BRAF testing were publicly reimbursed at current rates, the incremental profiling cost with OCAv3 would be $90 CAD per case. Conclusions: Although a key barrier to implementation is lack of funding for NGS in the Canadian publicly funded system, the OCAv3 consolidates genomic testing, identifies additional actionable targets, and substantially increases clinical trial eligibility for patients at a small incremental cost. Clinical trial information: NCT03558165.

scholarly journals A Remarkable Remission: Treating HMA Refractory Transforming MDS with Single-Agent Low-Dose Cytarabine Leading to an Ongoing Six-Year OS

2020 ◽  
Vol 2020 ◽  
pp. 1-3 ◽  
Author(s):  
David Palmer ◽  
Lydia Jones
Keyword(s):  
High Risk ◽  
Low Dose ◽  
Therapeutic Option ◽  
Treatment Options ◽  
Intensive Therapy ◽  
Single Agent ◽  
Standard Of Care ◽  
Cell Transplant ◽  
Investigational Agents ◽  
Low Dose Cytarabine

Hypomethylating agents (HMA) are the standard of care for patients ≥65 years with intermediate-high risk myelodysplastic syndrome (MDS) unsuitable for intensive therapy or stem cell transplant (SCT). However, many patients will develop relapse/refractory disease, at which point limited treatment options remain. There has been a lot of research into investigational agents following HMA failure, especially now into targeted therapy, but there is no final consensus or convincing data to guide clinicians. Low-dose cytarabine (LDAC) has been in the armamentarium for some time, but the value of LDAC is judged differently by various guidelines. Nevertheless, in a subgroup of patients who fail on a HMA and wish to continue treatment, LDAC may still have the potential to improve overall survival (OS). In this case report, we present an 85-year-old gentleman with HMA refractory high-risk/transforming MDS (with a noncomplex karyotype) achieving an ongoing six-year OS with single-agent second-line LDAC. LDAC may therefore still be considered by clinicians as a therapeutic option, but when available, patients should be enrolled on a clinical trial.

scholarly journals Newly Diagnosed Myeloma in 2020

2020 ◽  
pp. e144-e158 ◽  
Author(s):  
Philippe Moreau ◽  
Cyrille Touzeau ◽  
Ravi Vij ◽  
Scott R. Goldsmith ◽  
Ashley E. Rosko
Keyword(s):  
Older Adults ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Standard Of Care ◽  
Newly Diagnosed ◽  
New Agents ◽  
Specific Patient ◽  
Clinical Endpoints ◽  
Frontline Treatment ◽  
Treatment Tolerance

Over the last few years, there has been great progress in the treatment of multiple myeloma (MM), with many new agents and combinations having been approved and being now routinely incorporated into treatment strategies for newly diagnosed patients. As a result, patients are experiencing benefits in terms of survival and better tolerance. However, the multitude of treatment options also presents a challenge to select the best options tailored to the specific patient situation. Frontline autologous stem cell transplantation (ASCT) is the standard of care for fit patients younger than age 71 who are newly diagnosed with MM, and triplet combinations are the backbone of induction therapy before ASCT. Post-transplant consolidation and prolonged lower-intensity maintenance are two strategies that have been used to deepen responses and delay progression. For older patients not eligible for ASCT, lenalidomide (len) is increasingly being used as part of frontline therapy, and current approaches are now targeting combinations of anti-CD38 antibodies. Strategies for selecting therapeutic regimens for older adults newly diagnosed with MM can be augmented with use of predictive tools to better capture physiologic age and estimate treatment tolerance. Here we review a decade of trials identifying clinical endpoints and toxicities relevant for the frontline treatment of younger patients and older adults.

scholarly journals Recent advances in understanding colorectal cancer

F1000Research ◽  
2018 ◽  
Vol 7 ◽  
pp. 1528 ◽  
Author(s):  
Sebastian Stintzing
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Treatment ◽  
Immune Checkpoint ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Molecular Testing ◽  
Effective Treatment Option ◽  
Chemotherapy Study

The achievements in the treatment of metastatic colorectal cancer during recent years are based on a better understanding of the disease and individualized regimen planning. In adjuvant treatment, the highly important IDEA (International Duration Evaluation of Adjuvant Chemotherapy) study has shown that treatment duration can safely be reduced in selected patient populations. In patients with pN1 and pT1-pT3 tumors, 3 months of treatment with 5-fluorouracil and oxaliplatin is comparable with respect to 3-year survival rate to 6 months of treatment. For patients with N2 tumors, 6 months of treatment should stay the standard of care. The limitation of the duration of the adjuvant treatment is significantly reducing the chemotherapy-induced morbidity. New studies will explore the use of immune-checkpoint inhibitors in the adjuvant setting in microsatellite-instable (MSI) tumors. In metastatic disease, next to the required molecular testing for RAS and BRAF mutations, MSI testing is recommended. In the rare group of patients with a MSI tumor, immune-checkpoint inhibition is changing the course of the disease dramatically. Therefore, it is important to identify those patients early. For the RAS-mutant cases, no new and targeted treatment options have been identified yet. An optimal treatment strategy for those patients is urgently needed. RAS wild-type patients with tumors derived from the left side of the colon (splenic flexure to rectum) should be treated in first line with epithelial growth factor receptor (EGFR) antibodies. This selection by a molecular and a clinical marker increased the benefit derived by EGFR antibodies dramatically and defined the most effective treatment option for those patients. New selection criteria based on gene expression, methylation, and other molecular changes are explored and will further influence our therapeutic strategies in the future.

scholarly journals Case-Based Review: newly diagnosed glioblastoma

2015 ◽  
Vol 2 (3) ◽  
pp. 106-121 ◽  
Author(s):  
Derek R. Johnson ◽  
Shannon E. Fogh ◽  
Caterina Giannini ◽  
Timothy J. Kaufmann ◽  
Aditya Raghunathan ◽  
...  
Keyword(s):  
Treatment Options ◽  
Standard Of Care ◽  
Primary Brain Tumor ◽  
Newly Diagnosed ◽  
Therapeutic Approaches ◽  
Who Grade ◽  
Current Therapies ◽  
Newly Diagnosed Glioblastoma ◽  
New Treatments ◽  
Active Investigation

Abstract Glioblastoma (WHO grade IV astrocytoma) is the most common and most aggressive primary brain tumor in adults. Optimal treatment of a patient with glioblastoma requires collaborative care across numerous specialties. The diagnosis of glioblastoma may be suggested by the symptomatic presentation and imaging, but it must be pathologically confirmed via surgery, which can have dual diagnostic and therapeutic roles. Standard of care postsurgical treatment for newly diagnosed patients involves radiation therapy and oral temozolomide chemotherapy. Despite numerous recent trials of novel therapeutic approaches, this standard of care has not changed in over a decade. Treatment options under active investigation include molecularly targeted therapies, immunotherapeutic approaches, and the use of alternating electrical field to disrupt tumor cell division. These trials may be aided by new insights into glioblastoma heterogeneity, allowing for focused evaluation of new treatments in the patient subpopulations most likely to benefit from them. Because glioblastoma is incurable by current therapies, frequent clinical and radiographic assessment is needed after initial treatment to allow for early intervention upon progressive tumor when it occurs.

scholarly journals New and emerging therapies for acute myeloid leukaemia

2018 ◽  
Vol 66 (8) ◽  
pp. 1088-1095 ◽  
Author(s):  
Julian R Davis ◽  
David J Benjamin ◽  
Brian A Jonas
Keyword(s):  
Intensive Therapy ◽  
B Cell Lymphoma ◽  
Gemtuzumab Ozogamicin ◽  
Newly Diagnosed ◽  
Antigen Receptors ◽  
Engineered T Cells ◽  
Ubiquitination Pathway ◽  
Poor Outcomes ◽  
New Treatments ◽  
Acute Myeloid

The treatment of acute myeloid leukemia (AML) has remained relatively unchanged for the past 3–4 decades with generally poor outcomes, especially in elderly populations unfit for intensive therapy. Recent advancements, however, have identified several cytogenetic and molecular markers that have not only improved prognostication but have also led to the development of several new targeted therapies for specific subpopulations. In 2017, the US Food and Drug Administration approved four new treatments with indications for fms like tyrosine kinase 3 (FLT3)-mutated AML (midostaurin), newly diagnosed or relapsed/refractory CD33+AML (gemtuzumab ozogamicin), newly diagnosed therapy-related AML or AML with myelodysplasia-related changes (CPX-351) and relapsed/refractory AML with an isocitrate dehydrogenase (IDH)2 mutation (enasidenib). These newly approved therapies have demonstrated improved response in their target populations in several pivotal clinical trials with some also demonstrating improved overall survival. Additional novel therapies in development for AML include agents that target B cell lymphoma 2, FLT3, IDH1, the ubiquitination pathway, as well as cell therapy using engineered T cells with chimeric antigen receptors. This review provides a summary of the four newly approved therapies for AML, as well as several promising therapies currently in development.

scholarly journals Clinical Characteristics and Outcomes of AML Patients Treated with Frontline CPX 351 or HMA/Venetoclax: A Single Institution's Experience

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1252-1252
Author(s):  
Aleksander L. Chojecki ◽  
Justin Arnall ◽  
Danielle Boselli ◽  
Kristyn Y. DiSogra ◽  
Allison Karabinos ◽  
...  
Keyword(s):  
Research Funding ◽  
Clinical Characteristics ◽  
Treatment Options ◽  
Standard Of Care ◽  
Response Rates ◽  
Similar Response ◽  
Refractory Disease ◽  
Newly Diagnosed ◽  
Frontline Treatment ◽  
To Receive

Abstract Introduction: Treatment options for newly diagnosed patients (pts) with acute myeloid leukemia (AML) have historically been limited. The combination of a hypomethylating agent and venetoclax (HMA/Ven) has emerged as standard of care treatment for elderly and/or unfit pts with newly diagnosed AML. Liposomal cytarabine/daunorubicin (CPX-351) has also become standard of care therapy for pts with AML with myelodysplasia related changes or therapy-related AML. Despite being an intensive regimen, CPX-351 may have a more favorable toxicity profile compared to other intensive regimens. As a result, CPX-351 may be offered to older fit pts who may not have been candidates for traditional induction regimens. As the landscape for frontline treatment options evolves, there are now overlapping pt populations who may be eligible for either frontline treatment option. A retrospective study that included clinical trial pts demonstrated similar response rates in pts treated with HMA/Ven and CPX-351 (Asghari Blood 2019). Similarly, a study of secondary AML pts receiving HMA/Ven and CPX-351 showed no difference in remission rate or survival (Salhotra Am J Hematol 2021). There remains a shortage of data describing clinical characteristics of pts selected for and treated with standard-of-care HMA/Ven and CPX-351. We present a study on our center's experience. Methods: The purpose of this study was to evaluate the clinical characteristics and outcomes of adult pts with newly diagnosed AML who were treated with either CPX-351 or HMA/Ven as initial therapy. Consecutive pts treated with either of these two induction therapies between August 2017 and June 2021 were evaluated retrospectively. Pts were eligible for response evaluation if they received at least 3 doses of CPX-351 or 28 days (1 cycle) of venetoclax ("response cohort"). All pts treated with CPX-351 or HMA/Ven were included in survival analysis ("survival cohort"). Response assessment is based on ELN-2017 criteria. Pt characteristics were described and compared using Fisher's Exact tests. Kaplan-Meier methods were used to summarize overall survival, and log-rank tests were used for the comparison of frontline therapies. Cox proportional-hazards regression estimated hazard ratio (HR), 95% confidence interval (CI), and interactions between frontline therapy and age at induction start. Results : A total of 79 pts were identified receiving frontline HMA/Ven or CPX-351; 61 pts (77%) were evaluable for response. Of the response cohort, 21 (34%) were treated with CPX-351 and 40 (66%) with HMA/Ven; pt characteristics are described in Table 1. CPX-351 pts were younger at start of induction (P<0.001); many pts in both treatment groups had unfavorable ELN risk scores at diagnosis (CPX 43%, HMA/Ven 41%; P>0.99). 33% and 23% of the HMA/Ven cohort achieved CR and CRi respectively; in the CPX-351 cohort 57% and 5% achieved CR and CRi respectively. A greater fraction of CPX-351 pts proceeded to allogeneic stem cell transplant than HMA/Ven pts (67% vs 23%; P<0.001). No differences were detected in achievement of MRD negativity by flow cytometry (P=0.51) or molecular profile (P=0.52). Median follow-up for all pts was 18.9 months; 42 deaths occurred. Differences in survival between the frontline therapies were not detected in the survival cohort (HR, 1.31; 95% CI, 0.67 to 2.57; P=0.43) nor the response cohort (HR, 0.97; 95% CI, 0.45 to 2.09; P=0.93); these results were unaffected by adjustments for age at induction, ELN risk score, and transplant status. 8 pts who initially received CPX-351 and had refractory disease later went on to receive HMA/Ven reinduction; 2 achieved CRi, 2 MLFS, 3 Refractory and 1 Death in Aplasia. 1 pt who initially received HMA/Ven with refractory disease went on to receive CPX-351. This pt was refractory to CPX-351. Conclusion: HMA/Ven and CPX-351 are effective frontline treatment options with similar response rates and survival outcomes in newly diagnosed adults with AML. Pts treated with CPX-351 were younger and more likely to proceed with allogeneic transplantation, in line with standard practice. Though there was heterogeneity in pt populations, age did not appear to affect outcomes. As the landscape for standard-of-care upfront treatment for AML continues to evolve, further studies are warranted to determine optimal therapy selection and sequencing. Figure 1 Figure 1. Disclosures Arnall: Novo Nordisk: Speakers Bureau. Symanowski: Carsgen: Consultancy; Immatics: Consultancy, Other: DSMB Member; Eli Lilly: Consultancy, Other: DSMB Member. Avalos: JUNO: Membership on an entity's Board of Directors or advisory committees. Copelan: Amgen: Consultancy. Grunwald: Cardinal Health: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Agios: Consultancy; Janssen: Research Funding; PRIME: Other; Karius: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Blueprint Medicines: Consultancy; Gilead: Consultancy; Incyte: Consultancy, Research Funding; Amgen: Consultancy; Med Learning Group: Other; Sierra Oncology: Consultancy; MDEdge: Other; PER: Other; Trovagene: Consultancy; Stemline: Consultancy.

Sign in / Sign up

Export Citation Format

Share Document