Targeted Therapy in Hematologic Malignancies

2010 ◽  
pp. 293-323
Author(s):  
Barbara Zehnbauer ◽  
Mona Nasser
Keyword(s):  
Targeted Therapy ◽  
Hematologic Malignancies

Targeted agent use in patients with cancer at the end of life.

2012 ◽  
Vol 30 (34_suppl) ◽  
pp. 215-215 ◽  
Author(s):  
David Hui ◽  
Meghan Sri Karuturi ◽  
Kimberson Cochien Tanco ◽  
Jung Hye Kwon ◽  
Sun Hyun Kim ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
End Of Life ◽  
Hematologic Malignancies ◽  
Poor Quality ◽  
Chemotherapeutic Agents ◽  
Concurrent Chemotherapy ◽  
Targeted Agents ◽  
Patients With Cancer ◽  
Lung Malignancies ◽  
Targeted Agent

215 Background: Chemotherapy use at the end of life is considered an indicator of poor quality of care. The use of targeted agent has not been well characterized. In this study, we determined the frequency and predictors of targeted therapy use in the last 30 days of life. Methods: All adult patients residing in the Houston area who died of advanced cancer between September 1, 2009 and February 28, 2010 and had contact with our institution within the last three months of life were included. We collected baseline demographics and data on chemotherapy and targeted agents. Results: 816 patients were included: average age 62 (range 21 to 97), female 48% and White 61%. The median interval between the last treatment and death was 47 (interquartile range 21 to 97) days for targeted agents and 57 (26 to 118) days for chemotherapeutic agents. 116 (14%) patients received targeted agents and 147 (18%) received chemotherapy within the last 30 days of life. 43 (5%) patients received targeted agents had concurrent chemotherapy. The most common targeted agents in the last 30 days of life were erlotinib (n=25), bevacizumab (n=20) and rituximab (n=11). In multivariate analysis, younger age, hematologic, and lung malignancies were associated with increased targeted agent use in the last 30 days of life (Table). Conclusions: Targeted agents were used as often as chemotherapy at the end of life, particularly among younger patients and those with hematologic malignancies. Guidelines on targeted therapy use at the end of life are needed. [Table: see text]

Activity and tolerability of SL-401, a targeted therapy directed to the interleukin-3 receptor on cancer stem cells and tumor bulk, as a single agent in patients with advanced hematologic malignancies.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 7029-7029 ◽  
Author(s):  
Arthur E. Frankel ◽  
Marina Konopleva ◽  
Donna Hogge ◽  
David Rizzieri ◽  
Christopher Brooks ◽  
...  
Keyword(s):  
Stem Cells ◽  
Targeted Therapy ◽  
Cancer Stem Cells ◽  
Single Agent ◽  
Hematologic Malignancies ◽  
Single Cycle ◽  
Long Term Outcome ◽  
Interleukin 3 ◽  
Wide Range ◽  
Refractory Aml

7029^ Background: SL-401 is a novel biologic targeted therapy directed to the interleukin-3 receptor (IL-3R). IL-3R is overexpressed on cancer stem cells (CSCs) and tumor bulk relative to normal hematopoietic cells in a wide range of hematologic malignancies including AML and blastic plasmacytoid dendritic cell neoplasm (BPDCN). Since SL-401 targets both leukemia blasts and CSCs, tumor regression and improvement in long-term outcome is expected. The clinical activity and side effect profile of SL-401 were evaluated in a multicenter Phase I/II trial of patients with advanced hematologic cancers. Methods: Eighty-one patients with advanced hematologic cancers, including relapsed or refractory AML (n = 59) and heavily pretreated BPDCN (n = 4), have been enrolled. Patients received a single cycle of SL-401 via 15-minute IV infusion to determine the maximum tolerated dose (MTD) and assess antitumor activity. Results: A single cycle of SL-401 demonstrated single agent activity in relapsed or refractory AML patients, including 2 durable CRs of 8 and 25+ months duration and multiple cases of blast reductions. SL-401, when delivered at therapeutically relevant doses, was associated with > 3-fold greater median overall survival (OS) in AML patients who received 2+ prior lines of treatment relative to historical results. In addition, 3 heavily pre-treated patients with BPDCN, an uncommon malignancy that expresses high levels of IL-3R and is ultrasensitive to SL-401 (IC50 values in the femtomolar [10-15 M] range), had CRs, with durations of 5, 3+ and 1+ months. The MTD was 16.6 µg/kg/day; the dose-limiting toxicities of hypoalbuminemia and edema, which are manifestations of capillary leak, occurred at 22.1 µg/kg/day. Other ≥ Grade 3 adverse events included transient transaminase elevations. There was no treatment-related myelosuppression. Conclusions: SL-401 was well tolerated and demonstrated single agent activity in patients with relapsed or refractory AML and BPDCN. Based on these findings, single agent SL-401 given in multiple cycles will be advanced into pivotal studies of AML (3rd-line) and BPDCN. Clinical trial information: NCT00397579.

Chronic Myeloid Leukemia 2010: Where Are We Now and Where Can We Go?

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 122-128 ◽  
Author(s):  
Jerald P. Radich
Keyword(s):  
Targeted Therapy ◽  
Chronic Myeloid Leukemia ◽  
Tyrosine Kinases ◽  
Myeloid Leukemia ◽  
Second Generation ◽  
Hematologic Malignancies ◽  
The Other ◽  
Molecular Tools ◽  
Molecular Monitoring ◽  
First And Second Generation

Abstract Chronic myeloid leukemia is a model of how the molecular understanding of a disease can provide the platform for therapy and diagnostics. Clinicians are now empowered with first- and second-generation tyrosine kinases, as well as molecular tools to monitor disease and characterize resistance. However, there are still unanswered questions regarding optimization of therapy, the utility of molecular monitoring, and the search (or need) of “cure” that bears thought. In this review, we will discuss these issues, as they provide a roadmap for what may lie ahead in the therapy of other hematologic malignancies, particular the other myeloproliferative syndromes, where specific genetic lesions, and targeted therapy, are now being realized.

scholarly journals Targeting CD123 in hematologic malignancies: identifying suitable patients for targeted therapy

2021 ◽  
pp. 1-19
Author(s):  
Mrinal M. Patnaik ◽  
Tariq I. Mughal ◽  
Christopher Brooks ◽  
Ross Lindsay ◽  
Naveen Pemmaraju
Keyword(s):  
Targeted Therapy ◽  
Hematologic Malignancies

Targeted Therapy for Hematologic Malignancies

2005 ◽  
Vol 12 (2) ◽  
pp. 82-90 ◽  
Author(s):  
Philip Kuriakose
Keyword(s):  
Monoclonal Antibodies ◽  
Targeted Therapy ◽  
Small Molecules ◽  
Targeted Therapies ◽  
Hematologic Malignancies ◽  
Therapeutic Benefit ◽  
Specific Cell ◽  
Surface Receptors ◽  
Toxic Approach ◽  
Specific Cell Surface

Background: The introduction of monoclonal antibodies, either as native molecules or conjugated to radioisotopes or other toxins, has led to new therapeutic options for patients with hematologic malignancies. In addition, the use of small molecules against specific cell surface receptors, enzymes, and proteins has become an important strategy in the treatment of such disorders. Methods: The author reviewed the published clinical trials of monoclonal antibody and other targeted therapies in hematologic malignancies. Results: Results from several trials demonstrate a therapeutic benefit for the use of monoclonal antibodies (either native or conjugated) and other targeted therapies, used alone or in combination with standard cytotoxic chemotherapy. Conclusions: Targeted therapy of hematologic malignancies seems to be an effective and less toxic approach to the treatment of such disorders. Nevertheless, additional studies are needed to determine where and when such management fits into a therapeutic regimen for any given disorder, whether upfront or as salvage therapy, alone or in combination with chemotherapy (concurrent or sequential).

Long non-coding RNA PVT1 as a novel candidate for targeted therapy in hematologic malignancies

2018 ◽  
Vol 98 ◽  
pp. 54-64 ◽  
Author(s):  
Mohammad Houshmand ◽  
Narjes Yazdi ◽  
Alireza Kazemi ◽  
Amir Atashi ◽  
Amir Ali Hamidieh ◽  
...  
Keyword(s):  
Targeted Therapy ◽  
Hematologic Malignancies ◽  
Non Coding Rna ◽  
Long Non Coding Rna

scholarly journals Optimal Molecular Methods in Detecting p190BCR-ABLFusion Variants in Hematologic Malignancies: A Case Report and Review of the Literature

2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Rebecca J. Sonu ◽  
Brian A. Jonas ◽  
Denis M. Dwyre ◽  
Jeffrey P. Gregg ◽  
Hooman H. Rashidi
Keyword(s):  
Targeted Therapy ◽  
Kinase Inhibitors ◽  
Rare Variants ◽  
Lymphoblastic Leukemia ◽  
Quantitative Polymerase Chain Reaction ◽  
False Negative ◽  
Hematologic Malignancies ◽  
Molecular Diagnostic ◽  
Diagnostic Pcr ◽  
Negative Results

Patients with BCR-ABL1 positive hematologic malignancies and Philadelphia-like B-lymphoblastic leukemia (B-ALL) are potential candidates for targeted therapy with tyrosine kinase inhibitors (TKI). Before TKIs, patients with B-ALL had a much worse prognosis and current treatments with targeted TKI therapy have improved outcomes. Thus, the detection of BCR-ABL1 is crucial and a false negative BCR-ABL1 result may adversely affect patient care. We report a case of a 76-year-old male with a new diagnosis of B-ALL who was initially found to be BCR-ABL1 negative by quantitative polymerase chain reaction (PCR). A concurrent qualitative PCR was performed which detected a positive BCR-ABL1 result that was confirmed by a next generation sequencing (NGS) based assay and identified as the rare fusion variant e1a3 of p190BCR-ABL. Based on this result, the patient was placed on dasatinib as a targeted therapy. In the era of molecular diagnostic medicine and targeted therapy, it is essential to have an understanding of the limitations of molecular assays and to follow a comprehensive diagnostic approach in order to detect common abnormalities and rare variants. Incorporating NGS methods in an algorithmic manner into the standard diagnostic PCR-based approach for BCR-ABL1 will aid in minimizing false negative results.

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