Article
Oncology
Naval Daver, Alexander E. Perl, Joseph Maly, Mark Levis, Ellen Ritchie, Mark Litzow, James McCloskey, Catherine C. Smith, Gary Schiller, Terrence Bradley, Ramon Tiu, Kiran Naqvi, Monique Dail, Deanna Brackman, Satya Siddani, Jing Wang, Brenda Chyla, Paul Lee, Jessica K. Altman
Summary: Combining gilteritinib with venetoclax has shown promising results in treating relapsed/refractory FLT3-mutated AML, with high rates of response and molecular remission regardless of prior FLT3 inhibitor therapy.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Medicine, General & Internal
Harry P. Erba, Pau Montesinos, Hee-Je Kim, Elzbieta Patkowska, Radovan Vrhovac, Pavel Zak, Po -Nan Wang, Tsvetomir Mitov, James Hanyok, Yasser Mostafa Kamel, Jaime E. Connolly Rohrbach, Li Liu, Aziz Benzohra, Arnaud Lesegretain, Jorge Cortes, Alexander E. Perl, Mikkael A. Sekeres, Herve Dombret, Sergio Amadori, Jianxiang Wang, Mark J. Levis, Richard F. Schlenk
Summary: The aim of the study was to compare the effect of Quizartinib versus placebo on overall survival in patients with FLT3-ITD-positive newly diagnosed AML. The results showed that the addition of Quizartinib to standard chemotherapy can improve overall survival in adult patients with FLT3-ITD-positive newly diagnosed AML.
Article
Medicine, Research & Experimental
Friedrich Stoelzel, Sarah E. Fordham, Devi Nandana, Wei-Yu Lin, Helen Blair, Claire Elstob, Hayden L. Bell, Brigitte Mohr, Leo Ruhnke, Desiree Kunadt, Claudia Dill, Daniel Allsop, Rachel Piddock, Emmanouela-Niki Soura, Catherine Park, Mohd Fadly, Thahira Rahman, Abrar Alharbi, Manja Wobus, Heidi Altmann, Christoph Roellig, Lisa Wagenfuehr, Gail L. Jones, Tobias Menne, Graham H. Jackson, Helen J. Marr, Jude Fitzgibbon, Kenan Onel, Manja Meggendorfer, Amber Robinson, Zuzanna Bziuk, Emily Bowes, Olaf Heidenreich, Torsten Haferlach, Sara Villar, Benat Ariceta, Rosa Ayala Diaz, Steven J. Altschuler, Lani F. Wu, Felipe Prosper, Pau Montesinos, Joaquin Martinez-Lopez, Martin Bornhaeuser, James M. Allan
Summary: Precision medicine is important in improving outcomes for cancer patients, and in this study, it was found that elderly patients with acute myeloid leukemia (AML) who had somatic biallelic TET2 mutations were resistant to certain chemotherapies but sensitive to 5'-azacitidine (5'-Aza) hypomethylating monotherapy. Experimental evidence showed that cells with biallelic TET2 mutations were more sensitive to 5'-Aza compared to cells with monoallelic mutations. This study suggests the potential use of hypomethylating agents as a treatment option for chemoresistant AML patients with biallelic TET2 mutations and highlights the importance of considering mutant allele dosage in precision medicine for cancer patients.
Article
Pharmacology & Pharmacy
Allison Gaudy, Eric Laille, Rochelle Bailey, Simon Zhou, Barry Skikne, C. L. Beach
Summary: Researchers developed a population pharmacokinetic model to characterize the concentration-time profiles of oral azacitidine (AZA) in patients with AML, myelodysplastic syndrome, or chronic myelomonocytic leukemia. The study found that exposure parameters of oral-AZA were significantly associated with relapse-free survival, overall survival, and adverse events. The optimal dosing schedule for oral-AZA maintenance was determined to be 300 mg once daily for 14 days.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Multidisciplinary Sciences
Kun-Yin Qiu, Xiong-Yu Liao, Yong Liu, Ke Huang, Yang Li, Jian-Pei Fang, Dun-Hua Zhou
Summary: This study explores the relationship between FLT3/ITD allelic ratio and prognosis in pediatric AML patients and identifies an optimal threshold value, highlighting the importance of individualized treatment for pediatric AML.
NATURE COMMUNICATIONS
(2022)
Article
Medicine, General & Internal
Pau Montesinos, Christian Recher, Susana Vives, Ewa Zarzycka, Jianxiang Wang, Giambattista Bertani, Michael Heuser, Rodrigo T. Calado, Andre C. Schuh, Su-Peng Yeh, Scott R. Daigle, Jianan Hui, Shuchi S. Pandya, Diego A. Gianolio, Stephane de Botton, Hartmut Dohner
Summary: This study demonstrated that the combination therapy of oral ivosidenib and azacitidine showed better event-free survival and longer overall survival in patients with newly diagnosed IDH1-mutated acute myeloid leukemia.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Letter
Clinical Neurology
Lili-Naz Hazrati, Maryam Monajemzadeh, Zohreh Habibi, Bahar Moeini, Moeinadin Safavi
Summary: CNS tumor with BCOR internal tandem duplication is a newly proposed malignant tumor. The patient, an 18-month-old boy, presented with torticollis and vomiting caused by a cerebellar hemispheric mass extending to the cerebellopontine angle and foramen magnum. Histopathology examination revealed a moderately cellular tumor with microcystic formation, myxoid change, and atypical rosettes resembling Homer Wright rosettes. Illumina TruSight RNA Pan-Cancer NGS of the tumor genome detected BCOR gene exon 15 internal tandem duplications.
CHILDS NERVOUS SYSTEM
(2023)
Article
Hematology
Hartmut Doehner, Daniela Weber, Julia Krzykalla, Walter Fiedler, Gerald Wulf, Helmut Salih, Michael Luebbert, Michael W. M. Kuehn, Thomas Schroeder, Hans Salwender, Katharina Goetze, Joerg Westermann, Lars Fransecky, Karin Mayer, Bernd Hertenstein, Mark Ringhoffer, Hans-Joachim Tischler, Sigrid Machherndl-Spandl, Anika Schrade, Peter Paschka, Verena Gaidzik, Frauke Theis, Felicitas Thol, Michael Heuser, Richard F. Schlenk, Lars Bullinger, Maral Saadati, Axel Benner, Richard Larson, Richard Stone, Konstanze Doehner, Arnold Ganser
Summary: This study evaluated the efficacy of midostaurin in combination with intensive chemotherapy, followed by allogeneic hematopoietic-cell transplantation (HCT) and a 1-year midostaurin maintenance therapy, in adult patients with acute myeloid leukemia (AML) and fms-related tyrosine kinase 3 (FLT3) internal tandem duplication (ITD). The results showed that adding midostaurin to intensive therapy significantly improved the outcome in both younger and older AML patients with FLT3-ITD.
Article
Oncology
Jessica A. Pollard, Todd A. Alonzo, Robert Gerbing, Patrick Brown, Elizabeth Fox, John Choi, Brian Fisher, Betsy Hirsch, Samir Kahwash, Kelly Getz, John Levine, Lisa Eidenschink Brodersen, Michael R. Loken, Susana Raimondi, Katherine Tarlock, Andrew Wood, Lillian Sung, E. Anders Kolb, Alan Gamis, Soheil Meshinchi, Richard Aplenc
Summary: The study investigated the feasibility and efficacy of adding sorafenib, a multikinase tyrosine kinase inhibitor, to standard chemotherapy and as single-agent maintenance therapy in pediatric acute myeloid leukemia (AML) with high allelic ratio (HAR) FLT3/ITD mutations. The results showed that sorafenib can be safely added to conventional AML chemotherapy and may improve outcomes in this population. Patients treated with sorafenib had higher survival rates and disease-free survival rates compared to those who did not receive sorafenib.
JOURNAL OF CLINICAL ONCOLOGY
(2022)
Article
Oncology
Hiroto Inaba, Jolieke G. van Oosterwijk, John C. Panetta, Lie Li, Daelynn R. Buelow, James S. Blachly, Sheila Shurtleff, Ching-Hon Pui, Raul C. Ribeiro, Jeffrey E. Rubnitz, Stanley Pounds, Sharyn D. Baker
Summary: The combination therapy of crenolanib and sorafenib shows good efficacy and tolerability in FLT3-ITD positive AML, with rare emergence of FLT3-KD mutations.
CLINICAL CANCER RESEARCH
(2022)
Article
Medicine, General & Internal
Lin Ji, Wei Yang, Xiao-Feng Xu, Ya-Qing Xu
Summary: A 58-year-old man with acute myeloid leukemia (AML)-M5b accompanied by DNMT3A, FLT3-TKD, and IDH2 mutations and pulmonary tuberculosis (TB) was successfully treated with a combination of anti-TB drugs and anti-leukemia therapy. After multiple courses of treatment, the patient achieved complete remission.
FRONTIERS IN MEDICINE
(2023)
Article
Oncology
Nancy D. Ebelt, Edwin R. Manuel
Summary: Cancer cells can escape surveillance through epigenetic modifications, while hypomethylating agents (HMAs) have shown promise as a milder treatment option for leukemia patients. In this study, HMAs were tested on murine leukemias and found to re-establish immune-related gene expression, reduce leukemic burden, and improve survival. However, resistance and immune checkpoint protein expression were observed.
Article
Multidisciplinary Sciences
Ting Liu, Jianan Rao, Wenting Hu, Bowen Cui, Jiaoyang Cai, Yuhan Liu, Huiying Sun, Xiaoxiao Chen, Yanjing Tang, Jing Chen, Xiang Wang, Han Wang, Wubin Qian, Binchen Mao, Sheng Guo, Ronghua Wang, Yu Liu, Shuhong Shen
Summary: This study identifies potential driver alterations in Chinese pediatric AML, which differ from Western populations, and proposes a prognostic risk classification model.
NATURE COMMUNICATIONS
(2022)
Article
Biochemical Research Methods
Sungyoung Lee, Choong-Hyun Sun, Heejun Jang, Daeyoon Kim, Sung-Soo Yoon, Youngil Koh, Seung Chan Na, Sung Im Cho, Man Jin Kim, Moon-Woo Seong, Ja Min Byun, Hongseok Yun
Summary: This study introduces a novel and efficient FLT3-ITD detection approach called ITDetect, which utilizes NGS data. ITDetect demonstrates higher accuracy and provides more detailed information compared to existing in silico methods. Validation experiments show that ITDetect has the highest concordance with experimental methods.
BMC BIOINFORMATICS
(2023)
Article
Biology
Xi Xu, Weiwei Ma, Guo Qiu, Li Xuan, Chong He, Tian Zhang, Jian Wang, Qifa Liu
Summary: In this study, we analyzed the genetic characteristics of sorafenib-resistant AML cells and found that they can promote BCL2 transcription by activating STAT3. By introducing the BCL2 inhibitor venetoclax, the chemotherapy sensitivity of AML cells to sorafenib can be enhanced.
Article
Hematology
Justin M. Watts, Maria R. Baer, Jay Yang, Thomas Prebet, Sangmin Lee, Gary J. Schiller, Shira N. Dinner, Arnaud Pigneux, Pau Montesinos, Eunice S. Wang, Karen P. Seiter, Andrew H. Wei, Stephane De Botton, Montserrat Arnan, Will Donnellan, Anthony P. Schwarer, Christian Recher, Brian A. Jonas, P. Brent Ferrell Jr, Christophe Marzac, Patrick Kelly, Jennifer Sweeney, Sanjeev Forsyth, Sylvie M. Guichard, Julie Brevard, Patrick Henrick, Hesham Mohamed, Jorge E. Cortes
Summary: This study evaluated the safety, pharmacokinetics, pharmacodynamics, and clinical activity of Olutasidenib in patients with acute myeloid leukemia or myelodysplastic syndrome with mutant IDH1. The results showed that Olutasidenib, as monotherapy or in combination with azacitidine, was well tolerated and exhibited meaningful clinical activity. These findings provide a rationale for further evaluation of Olutasidenib in different populations of patients with myeloid malignancies.
LANCET HAEMATOLOGY
(2023)
Article
Oncology
Nikhil Shri Sahajpal, Ashis K. Mondal, Harmanpreet Singh, Ashutosh Vashisht, Sudha Ananth, Daniel Saul, Alex R. Hastie, Benjamin Hilton, Barbara R. DuPont, Natasha M. Savage, Vamsi Kota, Alka Chaubey, Jorge E. Cortes, Ravindra Kolhe
Summary: The current genetic testing of myeloid cancers lacks resolution and is limited to specific genomic regions/genes. This study used a combination of high-resolution cytogenetic technology and next-generation sequencing to obtain a comprehensive genomic profile of these tumors. The combinatorial approach identified new genetic alterations and clinically relevant alterations in previously negative cases.
Article
Hematology
Mycal Casey, Lorriane Odhiambo, Nidhi Aggarwal, Mahran Shoukier, K. M. Islam, Jorge Cortes
Summary: Despite advances in cancer outcomes, there are significant health disparities in the treatment of lymphomas. This study examined the representation of different demographic groups in randomized controlled trials (RCTs) for lymphoma and found significant underrepresentation of black, Hispanic, and female patients. Geographic distribution of trials also limited access for patients in certain areas. Correcting enrollment disparities is crucial to ensure that the results of these trials are applicable to all populations.
Article
Oncology
Fabio Efficace, Francesco Cottone, Betina Yanez, Vamsi Kota, Fausto Castagnetti, Giovanni Caocci, Massimiliano Bonifacio, Andrea Patriarca, Isabella Capodanno, Maria Cristina Miggiano, Mario Tiribelli, Massimo Breccia, Luigia Luciano, Valentina Giai, Alessandra Iurlo, Elisabetta Abruzzese, Carmen Fava, Shira Dinner, Jessica K. Altman, Gianantonio Rosti, Jorge Cortes, Marco Vignetti, David Cella
Summary: Patient-reported symptom monitoring from the beginning of therapy in patients with CML may be critical to improve adherence to therapy and early molecular response rates. The current findings suggest that systematic monitoring of patient-reported symptoms is associated with high adherence rates.
Article
Oncology
Koji Sasaki, Kiyomi Morita, Hagop Kantarjian, Guillermo Garcia-Manero, Elias Jabbour, Farhad Ravandi, Marina Konopleva, Gautam Borthakur, William Wierda, Naval Daver, Koichi Takahashi, Courtney Dinardo, Guillermo Montalban Bravo, Ghayas C. Issa, Sherry A. Pierce, Kelly A. Soltysiak, Martha S. Tingen, Jorge E. Cortes
Summary: This study investigated the impact of geographic disparities on cancer survival. The study found that factors such as age, income, race, and distance to cancer centers were predictive of survival. The results showed significant disparities in cancer care based on geographic locations.
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Article
Oncology
May Garrett, Beverly Knight, Jorge E. Cortes, Michael W. Deininger
Summary: This study compared the impact of different doses of bosutinib on the efficacy and safety outcomes of patients with chronic phase chronic myeloid leukemia. The results showed that a starting dose of 400 mg QD had better tolerability and did not compromise efficacy compared to a dose of 500 mg QD.
Article
Economics
Jorge E. Cortes, Delphine Rea, Michael J. Mauro, Diana Tran, Pearl Wang, Kejal Jadhav, Aurore Yocolly, Koji Sasaki
Summary: This study assessed and compared the health care resource utilization (HCRU) rates of asciminib and bosutinib among 3 L+ patients with chronic myeloid leukemia in chronic phase (CML-CP) in the ASCEMBL trial. The results showed that asciminib-treated patients had lower resource utilization compared to bosutinib-treated patients over the long-term.
JOURNAL OF MEDICAL ECONOMICS
(2023)
Review
Hematology
Marisol Miranda-Galvis, Kellen C. Tjioe, E. Andrew Balas, Gagan Agrawal, Jorge E. Cortes
Summary: This article evaluates the impact of social determinants of health on the outcomes of patients with hematologic malignancies. The study found that factors such as education level, health insurance coverage, income level, and marital status significantly affect patients' survival rates. However, there are contradictory reports regarding the effect of distance to treatment centers on treatment outcomes. Additionally, data on transportation, debt, diet, and other factors are lacking.
Review
Hematology
Mahesh Swaminathan, Jorge E. E. Cortes
Summary: Gemtuzumab-ozogamicin (GO) is an ADC approved for the treatment of CD33(+) AML. Despite initial recall due to lack of efficacy and hepatotoxicities, subsequent phase 3 studies showed significant survival benefits with lower and fractionated doses of GO in combination with standard chemotherapy. GO at a dose of 6 mg/m(2) was associated with higher grade > 3 hepatotoxicities and VOD compared to 3 mg/m(2). GO has been reapproved in 2017 and is currently being studied for its role in combination therapies and MRD elimination in CD33(+) AML patients.
THERAPEUTIC ADVANCES IN HEMATOLOGY
(2023)
Meeting Abstract
Oncology
Martin C. Mueller, Jorge Cortes, Charles Chuah, Daniel J. DeAngelo, Michael Deininger, Francois Guilhot, Timothy Hughes, Franck E. Nicolini, Javier Pinilla-Ibarz, Delphine Rea, Gianantonio Rosti, Neil P. Shah, Moshe Talpaz, Vickie Lu, Thihan Padukkavidana, Hagop M. Kantarjian
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Jane Apperley, Jorge Cortes, Elias Jabbour, Andreas Hochhaus, Timothy Hughes, Charles Chuah, Hugues de Lavallade, Michael Deininger, Jeffrey H. Lipton, Elza Lomaia, Lori Maness, Michael Mauro, James McCloskey, Beatriz Moiraghi, Carolina Pavlovsky, Christine Rojas, Philippe Rousselot, Tomasz Sacha, Moshe Talpaz, Anna Turkina, Maria Undurraga Sutton, Xiaowei Ren, Alexander Vorog, Gianantonio Rosti
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Ehab Atallah, Michael Mauro, Koji Sasaki, Moshe Levy, Paul Koller, Daisy Yang, Dramane Laine, John Sabo, Ennan Gu, Jorge Cortes
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Aram Bidikian, Sreyashi Basu, Zhong He, Himachandana Atluri, Jabra Zarka, Michael Andreeff, Koji Sasaki, Elias Jabbour, Jorge E. Cortes, Padmanee Sharma, Ghayas C. Issa
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Joannie Clements, Cristina Ruiz, Andrea Damon, Peter Schuld, Pauline Frank, Cristina Constantinescu, Jorge Cortes
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)
Meeting Abstract
Oncology
Jorge Cortes, Michael Deininger, Elza Lomaia, Beatriz Moiraghi, Maria Undurraga Sutton, Carolina Pavlovsky, Charles Chuah, Tomasz Sacha, Jeffrey H. Lipton, James McCloskey, Philippe Rousselot, Gianantonio Rosti, Hugues de Lavallade, Christine Rojas, Anna Turkina, Moshe Talpaz, Michael Mauro, Vickie Lu, Alexander Vorog, Jane Apperley
CLINICAL LYMPHOMA MYELOMA & LEUKEMIA
(2023)