Released: December 02, 2019
The ASH annual meeting always features a plethora of new data on optimization of current therapies and emerging treatment strategies. As a hematologist with a focus on myeloproliferative neoplasms, the following ASH 2019 studies are among those that I am most excited about.
New Strategies for Ruxolitinib-Experienced Patients With Myelofibrosis The JAK1/2 inhibitor ruxolitinib has been the standard first-line therapy for patients with symptomatic and/or higher-risk myelofibrosis based on findings from the randomized phase III COMFORT-I and -II studies, which showed significant improvements in spleen responses, symptom reduction, and survival with ruxolitinib vs placebo and/or best available therapy. Despite this, the response to ruxolitinib is often finite. For patients who lose response to ruxolitinib, prognosis has historically been poor. Several agents and regimens are currently in clinical development for the management of patients with MF who are intolerant of or resistant to ruxolitinib, and we will see new data for several of these at ASH 2019. Of note, several of the agents listed below target novel molecules outside of the traditional JAK/STAT pathway, which is of great interest in the field.
One such agent is CPI‑0610, a small-molecule bromodomain and extraterminal domain inhibitor; preclinical data suggest that BET and JAK inhibition may have synergistic effects in myeloproliferative neoplasms (MPNs). At ASH, we will see results from the multicenter, open-label phase II MANIFEST study, in which (1) patients who were refractory to or intolerant of ruxolitinib were treated with CPI-0610 monotherapy, or (2) patients who were JAK inhibitor naive and anemic or who were receiving ruxolitinib but had demonstrated suboptimal responses with this agent were treated with ruxolitinib plus CPI-0610. MANIFEST will evaluate spleen volume response, transfusion independence after baseline transfusion dependence, and total symptom score. This study is novel in that it looks at multiple different subgroups of patients with MF and multiple aspects of responses to the experimental agent/regimen.
Another study of interest at ASH 2019 is a single-arm, open-label phase II study of navitoclax plus ruxolitinib for patients with MF and previous ruxolitinib experience. Navitoclax is a small-molecule inhibitor that binds to the BCL-2 family of proteins; there has been a lot of interest in targeting of BCL-2 in myeloid malignancies, most notably in AML and CLL, for which the efficacy of the BCL-2 inhibitor venetoclax has been demonstrated, suggesting a mechanism of action that could be exploited in multiple diseases. The current study will evaluate the effect of navitoclax plus ruxolitinib on spleen size reduction, symptom score, anemia response, and improvement in bone marrow fibrosis.
Also of potential interest is a phase IIa study of IMG‑7289 in patients with intermediate 2–risk or high-risk MF and resistance or intolerance to ruxolitinib. IMG‑7289 targets the lysine‑specific demethylase (LSD1), which is an important epigenetic modifier. Preclinical data published in 2018 supported the use of LSD1 inhibitors in patients with MF, and the data from the current presentation are highly anticipated.
Strategies for Patients With MF and Thrombocytopenia and Anemia Treatment options for patients with MF and thrombocytopenia represent an unmet need in the MPN field, as currently approved JAK inhibitors are labelled for use in patients with platelet counts of > 50 x 109/L. Several studies that will be presented at ASH assessed agents with the potential to address this need.
PAC203 was a randomized, dose‑finding phase II study of pacritinib for patients with MF and resistance or intolerance to ruxolitinib. Pacritinib is a JAK2 and IRAK1 inhibitor that had previously shown efficacy in a randomized phase III trial in the first-line setting for patients with high-risk MF (vs non-JAK inhibitor treatments). A second randomized phase III trial demonstrated that pacritinib was associated with improved symptoms and spleen response vs best available therapy (which included ruxolitinib) for patients with MF and platelets < 100 x 109/L. Although the development of pacritinib was put on hold by the FDA due to reports of patient deaths related to intracranial hemorrhage, cardiac failure, and cardiac arrest, the clinical hold was removed in 2017 and PAC203 was initiated. In this study, patients were randomized into 3 dosing arms: pacritinib at 200 mg BID, 100 mg BID, and 100 mg QD. Of importance, in this study, 43% of patients had profound thrombocytopenia with platelet counts of < 0.5 x 109/L. The ongoing randomized phase III PACIFICA study of pacritinib vs physician’s choice of therapy for patients with MF and severe thrombocytopenia will also be introduced.
The results of a phase I/II trial of tagraxofusp—also known as SL‑401—for patients with MF and ruxolitinib intolerance/resistance will also be reported. Tagraxofusp targets CD123 and is approved by the FDA for treating patients with blastic plasmacytoid dendritic cell neoplasms. CD123 is expressed in a variety of cells, including plasmacytoid dendritic cells and dendritic cells that share precursors with monocytes. Since monocytosis is associated with a poor prognosis in patients with MF, targeting CD123 in these patients may be a beneficial therapeutic strategy. Of importance, a large proportion of patients in the current study had a platelet count < 50 x 109/L.
Fedratinib is a JAK2 and FLT3 inhibitor that was recently approved by the FDA for patients with intermediate 2–risk or high-risk MF based on the randomized phase III JAKARTA trial, which demonstrated a significantly higher rate of spleen volume reduction with fedratinib vs placebo for patients with MF who were naive to JAK2 inhibitors. Continued research into the use of this agent will be presented at ASH, including an analysis of spleen and symptom responses associated with this agent in patients with low platelet counts (< 100 x 109/L) who were treated in JAKARTA or JAKARTA2, the latter of which was a single-arm phase II study of fedratinib for patients with intermediate-risk or high-risk MF previously treated with ruxolitinib.
The management of anemia in patients with MF is also an area of clinical need. At ASH 2019, we will see preliminary results from an ongoing, open-label phase II study of luspatercept (an erythroid maturation agent) for the management in patients with MF-associated anemia (either those not receiving ruxolitinib or RBC transfusions, those not receiving ruxolitinib but with RBC transfusion–dependent anemia, or those with anemia and on a stable dose of ruxolitinib). Of note, luspatercept was recently approved for treating anemia in adult patients with β-thalassemia who require regular RBC transfusions.
Your Thoughts What MPN studies are you most interested in at this year’s ASH meeting? Please answer the polling question on your screen and share your thoughts in the comments box.
Attending the 2019 ASH annual meeting in Orlando? Sign up here to attend CCO’s satellite symposium, “Approaches to the Individualized Management of MPNs: Best Practices and Guidance to Optimize Care,” on the evening of Friday, December 6, during which I will discuss patient case studies and recent advances in the treatment of MPNs with our esteemed panel, including Srdan Verstovsek, MD, PhD; Jean-Jacques Kiladjian, MD, PhD; and Alessandro M. Vannucchi, MD. Not attending ASH but still want to view this exciting educational event? Sign up here to watch the live simulcast from your computer. After ASH concludes, remember to check the CCO Web site for a downloadable slideset summarizing the data from these studies and more.
These Terms of Use ("Terms") apply to your use of the websites, mobile applications and other resources provided by Clinical Education Alliance LLC (“CEA”) and its affiliates (referred to collectively as "CEA," "us," "we" and "our") that are intended for use by healthcare professionals, which we refer to as the "CEA Network," including the personalized information and services that meet the needs and interests of users of the CEA Network such as medical news, reference content, clinical tools, applications, sponsored programs, advertising, email communications, continuing medical education, market research opportunities and discussion forums (collectively, the "Services"). You will always be able to view the most current version of these Terms by clicking on the Terms of Use link at the bottom of any page of a CEA Network property. Note that these Terms do not apply to our properties and services that display a link to different terms of use. In the event that we expand the CEA Network through our acquisition of another company and/or its properties, that company may operate its properties subject to its own terms of use accessible via a link on such properties until we integrate its practices with ours, at which point a link to these Terms will be displayed on its properties. By using the Services, you agree to these Terms, whether or not you are a registered member of the CEA Network. These Terms govern your use of the Services and create a binding legal agreement that we may enforce against you in the event of a violation. If you do not agree to all of these Terms of Use, do not use the Services!
We reserve the right to change these terms from time to time. The most current version may be viewed by clicking on the “Terms of Use” link at the bottom of designated pages on the Clinical Education Alliance Sites. Use of the Clinical Education Alliance Sites after the effective date constitutes acceptance of the amended Terms of Use. When you leave a CEA Web site and go to another Web site, different terms apply and CEA has no responsibility or liability for any content on those sites.
The Clinical Education Alliance Sites incorporate information, including modules, capsules, journal articles, medical news, references, interactive case studies, other continuing education material, downloadable software applications, advertising, and other healthcare information, which is intended for adults who are licensed healthcare professionals. This information is not intended to serve as a substitute for the healthcare professional’s clinical judgment. If you are a consumer who chooses to read this professional-level information on Clinical Education Alliance Sites, you should not use or rely on that information as professional medical advice or use it to replace any relationship with your physician or other qualified healthcare professional or any information they may have provided to you. For medical issues or concerns, including decisions about medications and other treatments, consumers should always consult their physician or, in serious cases, seek immediate assistance from emergency personnel.
The Content on the Clinical Education Alliance Sites is developed or selected in accordance with our published Editorial Policies. However, users access and use this material at their own risk. It is the reader’s job to evaluate the accuracy of any information and results from interactive programs found on the Clinical Education Alliance Site. If you are a healthcare professional, you should rely on your professional judgment in evaluating any and all information and confirm the information contained on the Clinical Education Alliance Sites with other sources and reliable third parties before basing any treatment or advice on it. If you are a consumer, you should evaluate the information together with your physician or another qualified healthcare professional.
THE CONTENT, APPLICATIONS, SOFTWARE, AND ALL OTHER MATERIAL ON THE CLINICAL EDUCATION ALLIANCE SITES ARE PROVIDED “AS IS” AND WITHOUT WARRANTY OF ANY KIND, EITHER EXPRESS OR IMPLIED, INCLUDING, BUT NOT LIMITED TO, ANY IMPLIED WARRANTIES OF MERCHANTABILITY, FITNESS FOR A PARTICULAR PURPOSE, OR NONINFRINGEMENT. ALL WARRANTIES, EXPRESS OR IMPLIED, ARE HEREBY DISCLAIMED. CLINICAL EDUCATION ALLIANCE SHALL NOT BE LIABLE FOR ANY SPECIAL, INCIDENTAL, OR CONSEQUENTIAL DAMAGES, INCLUDING, WITHOUT LIMITATION, PHYSICAL HARM OR INJURIES, LOST REVENUES, OR LOST PROFITS, RESULTING FROM THE USE OR MISUSE OF THE CLINICAL EDUCATION ALLIANCE SITES, OR ANY INFORMATION, APPLICATIONS, MATERIALS, OR SOFTWARE THEREON, EVEN IF CLINICAL EDUCATION ALLIANCE HAS BEEN ADVISED OF THE POSSIBILITY OF SUCH DAMAGES, OR FOR ANY CLAIM BY ANOTHER PARTY. CLINICAL EDUCATION ALLIANCE DOES NOT WARRANT THAT THIS SITE OR ANY APPLICATIONS OR SOFTWARE WILL BE FREE OF BUGS, INACCURACIES, OR ERRORS, NOR DOES CLINICAL EDUCATION ALLIANCE WARRANT THAT ANY SITE, SOFTWARE, OR APPLICATION IS FREE OF VIRUSES OR OTHER HARMFUL ELEMENTS.
A user’s use of the Clinical Education Alliance Sites, and any reliance on any materials, information, software, or applications, is at the user’s own risk. You agree that you hereby release Clinical Education Alliance and its affiliates, owners, respective directors, officers, employees, advertisers, authors, and contributors from any and all liability or obligations arising from the use of the Clinical Education Alliance Sites. A user’s sole remedy for any problem or concern is to exit the Web site or application. You agree that you will indemnify and hold Clinical Education Alliance harmless for any loss, damages, or liability suffered by Clinical Education Alliance as a result of your use of any Clinical Education Alliance Site or material, application, information, or software thereon or your submission of any material to Clinical Education Alliance. Clinical Education Alliance reserves the right to restrict or limit access to this Web site.
The Clinical Education Alliance Sites include interactive programs, clinical tools, and databases intended for the use of healthcare professionals. These materials are not intended as professional advice or recommendations of particular products. Physicians and other healthcare professionals who use our interactive programs, tools, or databases should exercise their own clinical judgment as to the results. Consumers who use the tools or databases do so at their own risk.
Individuals with any type of medical condition are specifically cautioned to seek professional medical advice before beginning any sort of health treatment. For medical concerns or issues, including decisions about medications and other treatments, users should always consult their physician or other qualified healthcare professional.
The entire contents and design of the Clinical Education Alliance Sites, including the software applications, tools, and databases, are protected under US and international copyright laws. These materials are owned by CEA or its affiliates or are used with permission of their owners or as otherwise authorized by law. All rights are reserved, worldwide. You may look at the Clinical Education Alliance Sites, download individual articles or applications to your personal computer or handheld device, and print a reasonable number of pages for your own personal reference. You must not remove any copyright notices from our materials. We reserve all our other rights. This means you may not sell, rewrite, or modify any content or other material found on any Clinical Education Alliance Site, redistribute it, put it on your own Web site, or use it for any commercial purpose without our prior written authorization.
The names of the CEA products and services are protected by trademark laws in the United States. Any use of our trademarks or service marks requires prior written approval from CEA.
You may link to a CEA Web site if your Web site offers products, services, or information of interest to the professional healthcare community. You are not allowed to link to the Clinical Education Alliance Sites if you post illegal, obscene, or offensive content or if the link is likely to have a negative impact on CEA’s reputation. Any other use, such as framing any part of a CEA Web site or incorporating any CEA content into another Web site, product, or application, requires advance written permission from Clinical Education Alliance. Clinical Education Alliance assumes no responsibility for any Web sites or materials that are linked to Clinical Education Alliance Sites or materials.
Clinical Education Alliance makes some software and accompanying documentation available for downloading from our Web sites and/or from iTunes. These materials are protected by copyrights under US and international law and are owned by Clinical Education Alliance or companies that have licensed the software to us. We do not transfer any ownership rights in software or documentation to you when you download it from our Web site and/or directly from iTunes. You may use the software and accompanying documentation for their intended purpose. You are not authorized to further copy or distribute the software and accompanying documentation, nor may you attempt to recreate or reverse engineer our software or applications. In addition, some software available for downloading from our Web sites and/or from iTunes is subject to US export controls. By downloading or using such software, you are representing to us that your download of such software complies with these controls.
If you are affiliated with the US government, please note that the software and documentation available on our Web sites and/or directly from iTunes are “commercial items,” as that term is defined in 48 C.F.R. 2.101 (October 1995), consisting of “commercial computer software” and “commercial computer software documentation,” as such terms are used in 48 C.F.R. 12.212 (September 1995). Consistent with 48 C.F.R. 12.212 and 48 C.F.R. 227.7202-1 through 227.7202-4 (June 1995), all US government end users acquire the software and documentation with only those rights set forth herein.
Clinical Education Alliance offers users the opportunity to engage in social media interactions with both experts and other users of the sites. As with other online social media, users must exercise sound judgment in both the information that they post and in how they assess the postings of other users. As such, users are expected to adhere to the social media recommendations made by the American Medical Association when utilizing the social media capabilities of CEA sites. In particular, users must be cognizant of standards of patient privacy and confidentiality that must be maintained in all environments and must not post identifiable patient information on CEA sites. In social media interactions, users must maintain appropriate boundaries of the patient–physician/care provider relationship in accordance with professional ethical guidelines just as they would in any other context. Users acknowledge that privacy settings are not absolute and that once on the Internet, content posted by them may be copied by third parties and republished out of the control of Clinical Education Alliance. Thus, users should routinely monitor their own Internet presence to ensure that the personal information and content that they post and, to the extent possible, that is posted about them by others is accurate and appropriate.
Users are expected to refrain from submitting comments or messages that are defamatory, hateful, or obscene or that harass others. Users may not impersonate any other person or violate any other person’s or entity’s legal rights or submit falsified credentials or experiences. Users agree that they will not submit any materials that violate or infringe any copyrights, trademarks, patents, trade secret, or other intellectual property rights of any third party. Clinical Education Alliance retains all copyrights in the content posted by users to its sites. Clinical Education Alliance may adopt additional rules to govern use of social media, message boards or forums, to which users will be subject.
If you believe that any material on this Web site infringes your copyright, please notify us as follows, under the Digital Millennium Copyright Act (“DMCA”). To notify us, the DMCA requires that you: 1. Send an email notice to Clinical Education Alliance at customersupport@clinicaloptions.com. 2. Include the following information in your email: a. Identify the copyrighted work(s) you claim is infringed; b. Identify the material you claim is infringing the copyright(s) and give enough information for Clinical Education Alliance to locate that material; c. Include a physical or electronic signature of the copyright owner or a person authorized to act on the copyright owner’s behalf (the “Claimant”); d. Include the Claimant’s name, address, and telephone number(s); e. Include a statement that the Claimant has a good faith belief that use of the disputed material is not authorized by the copyright owner or his agent; and f. Include a statement, under penalty of perjury, that the information in the notification of copyright infringement is accurate and that the Claimant is the copyright owner or is authorized to act on behalf of the copyright owner.
If you believe any content or material on the Clinical Education Alliance Sites violates any laws, please notify customersupport@clinicaloptions.com. Please include details about your concerns and an email address for contacting you.
Clinical Education Alliance controls the Clinical Education Alliance Sites from its offices in the state of Virginia in the United States of America. The Clinical Education Alliance Sites can be accessed from any of the United States and from other countries worldwide. Since the laws of each state or country may differ, both you and Clinical Education Alliance agree that the laws of Virginia, without regard to conflicts of laws principles, will apply to all matters relating to use of the Clinical Education Alliance Sites and materials, including software and applications.
Clinical Education Alliance makes no representation that materials on these sites are appropriate or available for use in countries aside from the United States. Accessing the Clinical Education Alliance Sites from territories where their contents are illegal is prohibited. Those who choose to access these sites from other locations do so at their own risk and are responsible for compliance with any and all applicable local laws or regulations.
By downloading or accessing materials on the Clinical Education Alliance Sites and/or directly from iTunes or registering with us, you agree to all the terms and conditions in this agreement, including the Terms of Use and Privacy Policy. If you disagree with any of these Terms of Use or Privacy Policy, please refrain from using the Clinical Education Alliance Sites or materials.
Because we provide education for healthcare professionals, we pay special attention to privacy issues. The purpose of our Privacy Policy is to identify the information we may collect about you, describe the uses we may make of your information and the security measures we take to protect it, and discuss your options for controlling your information. You can review our Privacy Policy by clicking on the “Privacy Policy” link at the bottom of designated pages on the Clinical Education Alliance Sites.
If you fail to comply with these terms, we have the right to suspend or eliminate your account and remove any information you have placed on our site, including your registration information. We may also take any legal action we think is appropriate. If there is any dispute between us concerning this agreement or your use of any Clinical Education Alliance Site or materials or applications, we both agree to submit the dispute to nonbinding mediation, followed by binding arbitration. Both the mediation and the arbitration will be governed under the rules of the American Arbitration Association, and the venue for the arbitration will be Virginia.
For questions or concerns about these Terms of Use, please send an email to customersupport@clinicaloptions.com
These terms of use were last updated in July 2021.
You are leaving the site. The new destination site may have a different terms of use and privacy policy.
We've updated our ad policy. Please review our policy here. Click 'Agree' to accept. If you do not accept, you cannot proceed to the site.
By clicking "Agree," you are agreeing to our Privacy Policy, Terms & Conditions and Ad Policy.
Back
