Welcome!

News Feed Item

New Investigational Agent Targets Gene Signaling Pathways to Improve Therapeutic Response for Patients with Chronic Lymphocytic Leukemia

ATLANTA, Dec. 8, 2012 /PRNewswire-USNewswire/ -- The promising investigational targeted therapy ibrutinib and its mechanism of silencing gene communication pathways critical to the development of cancer may be an effective way to combat chronic lymphocytic leukemia (CLL), according to studies presented today at the 54th Annual Meeting of the American Society of Hematology (ASH).

CLL is a blood cancer that causes abnormal white blood cells called lymphocytes to accumulate in the blood, bone marrow, and in the lymph nodes or other organs, causing these organs to enlarge. Approximately 15,000 Americans are diagnosed with CLL every year; nearly 70 percent of those affected are 65 and older.[1], [2] For some patients with slower growing disease, physicians employ "watch and wait" strategies to minimize unnecessary treatment. However, patients with high-risk features such as rapidly progressing disease require prompt treatment to manage symptoms and reduce organ damage.

Ibrutinib is a specialized anti-cancer therapy that targets the Bruton's tyrosine kinase (BTK, an enzyme important in the development of CLL). As an inhibitor of BTK, ibrutinib selectively targets leukemia cells, promoting their death and preventing them from growing while leaving normal cells unharmed. Studies suggest this design allows the drug to more effectively treat the disease, with encouraging early results in harder-to-treat patient groups such as elderly untreated patients and those whose disease has become resistant to other therapies or those who have experienced disease recurrence after receiving other therapies. Two studies will present efficacy and safety results testing the compound alone and in combination with other currently used therapies for CLL.

"The evidence collected to date on ibrutinib demonstrates that it may have the potential to improve long-term prognosis for patients who are not sensitive to standard treatment," said Claire E. Dearden, MD, moderator of the press conference, Consultant Hematologist and Head of the CLL Unit at The Royal Marsden NHS Foundation Trust in London. "Equally important, the exciting efficacy and safety data that we are seeing for this drug in these studies underscore the significant progress we are making in our quest to better understand and attack the specific cellular targets responsible for CLL, particularly in these vulnerable patient populations."

This press conference will take place on Saturday, December 8, at 8:00 a.m. EST.

The Bruton's Tyrosine Kinase (BTK) Inhibitor Ibrutinib (PCI-32765) Promotes High Response Rate, Durable Remissions, and is Tolerable in Treatment Naive (TN) and Relapsed or Refractory (RR) Chronic Lymphocytic Leukemia (CLL) or Small Lymphocytic Lymphoma (SLL) Patients including Patients with High-Risk (HR) Disease: New and Updated Results of 116 Patients in Phase Ib/II Study [Abstract 189]

New research demonstrates that a novel investigational therapeutic agent called ibrutinib may be an effective and safe targeted treatment option for previously untreated, hard-to-treat, and relapsed patients with chronic lymphocytic leukemia (CLL). 

Primary treatment for CLL includes a combined chemotherapy-based regimen with fludarabine and cyclophosphamide, along with the immune therapy rituximab. While rituximab is effective, it is generally not well tolerated among elderly patients. Treatment with this drug also compromises the immune system by attacking both cancerous and normal cells, putting patients at risk for a range of infections and increasing their risk of developing treatment-related acute myeloid leukemia.

To understand if ibrutinib may be effective for elderly CLL patients and to identify which patients might benefit most from the drug, researchers enrolled 116 CLL patient participants in several treatment cohorts: patients who were never treated (the treatment-naive group), those who had received two or more prior therapies (the relapsed/refractory group), those who had relapsed within two years of treatment (the high-risk group), and those over age 65. Two oral dosing regimens (420 mg or 840 mg daily) of ibrutinib were used. The primary goal of the study was to determine the safety of the low and high doses; secondary objectives included efficacy, measures of the intensity of the drug's effect in the body, and the long-term safety of administering this therapy continuously until relapse.

The study found that response to therapy was high across the cohorts, with largely manageable toxicities.  Previously untreated elderly patients responded best to the agent, with 71 percent experiencing a complete or partial response at either treatment dose. The same response was observed in 67 percent of the relapsed patients and 50 percent of the high-risk patient cohort. After 22 months of follow-up, the disease had not progressed in 96 percent of previously untreated patients and 76 percent of relapsed and high-risk patients.

The treatment regimen was generally well-tolerated, as only non-severe side effects were observed, including diarrhea, fatigue, chest infection, rash, nausea, joint pain, and infrequent and transient low blood counts. Investigators found no evidence of cumulative toxicity or long-term safety concerns with a median follow-up of 16 months for treated patients. These results demonstrate ibrutinib's potential as a highly active, well-tolerated first-line therapy for CLL.

"As we learn more about how to target specific essential survival signals and communications pathways in cancer, we are improving our ability to effectively treat the disease while avoiding the toxicities of chemotherapy and potential relapse," said John C. Byrd, MD, lead author and Director of the Division of Hematology at The Ohio State University Comprehensive Cancer Center – James Cancer Hospital and Solove Research Institute in Columbus. "If we can replicate these high survival rates and good tolerability with ibrutinib through larger scale Phase III studies, we may find it to be an extremely valuable new therapy for not just elderly, but for all CLL patients."   

Dr. Byrd will present this study in an oral presentation on Sunday, December 9, at 5:00 p.m. EST at the Georgia World Congress Center in Thomas Murphy Ballroom 4, Level 5, Building B.

The BTK Inhibitor Ibrutinib (PCI-32765) in Combination with Rituximab is Well−Tolerated and Displays Profound Activity in High-Risk Chronic Lymphocytic Leukemia (CLL) Patients

[Abstract 187]

The combination of the novel investigational agent ibrutinib with an established therapeutic antibody, rituximab, may present a safer and more effective option than the current standard chemotherapy-based treatment regimen for patients with high-risk CLL.

While current chemotherapy-based treatment options for CLL patients are effective, they come with toxic side effects that are challenging for elderly patients. Physicians have long awaited new options that offer better tolerability. Ibrutinib is designed to selectively target leukemia cell growth, with the aim of effectively treating the disease without the toxicities of chemotherapy. Data from earlier studies of ibrutinib have shown it to be equally effective in both low- and high-risk CLL.

High-risk CLL patients typically have unfavorable responses to standard CLL therapies and a dismal outcome. Such patients are characterized by presence of chromosomal abnormalities (i.e., deletions of chromosome 17p or 11q) or short remissions (less than 3 years) after standard chemo-immunotherapy. To develop an alternative therapy regimen for this patient population, researchers explored the combination of ibrutinib and the anti-CD20 antibody rituximab in high-risk CLL.

In this Phase II study conducted at The University of Texas MD Anderson Cancer Center in Houston, ibrutinib was given in combination with rituximab to evaluate its potential to accelerate and improve CLL patient responses. Forty patients were treated with 420 mg of ibrutinib daily in combination with weekly rituximab for four weeks, followed by ibrutinib daily plus monthly rituximab until month six, followed by single-agent ibrutinib.

Positive responses to therapy were shown among the vast majority of treated patients. At four months of follow-up, the overall response rate was 85 percent and almost all (38 of 40) patients continued on therapy without disease progression. Of the 20 patients evaluable for early response, 17 achieved a partial remission. Patient health questionnaires also noted improvements in health and the quality of life of all treated patients. 

Overall, the regimen was well-tolerated among participants, with little severe toxicity that was largely unrelated and short in duration. After treatment with ibrutinib-rituximab (iR) combination therapy, most cases of early lymphocytosis (increase in white blood cells that is a sign of infection), due to the ibrutinib-induced shift of CLL cells from lymph node tissues into the blood, peaked early and resolved; at four months of follow-up, only three treated patients had lymphocytosis that had not yet resolved. This shorter lymphocytosis duration, when compared to single-agent use of ibrutinib, is presumably related to the addition of rituximab.

"We know that high-risk CLL patients struggle with the effects of standard chemo-immunotherapy and eventually become resistant. For these harder-to-treat patients, ibrutinib in combination with rituximab appears to be a safer option with high efficacy and without the related risks," said Jan Burger, MD, PhD, lead author and Associate Professor of Medicine in the Department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston. "Based on these promising results, we need larger-scale studies of ibrutinib-rituximab in high-risk CLL, with the goal of accelerating the development of this therapy for patients who most urgently need better options."

Dr. Burger will present this study in an oral presentation on Sunday, December 9, at 4:30 p.m. EST at the Georgia World Congress Center in Thomas Murphy Ballroom 4, Level 5, Building B.

American Society of Hematology 54th Annual Meeting

The study authors and moderator will be available for interviews after the press conference or by telephone. Additional press briefings will take place throughout the meeting on efforts to reduce toxicity and improve survival for blood cancer therapy, strategies to increase the efficacy and safety of treatments for bleeding and clotting disorders, new targeted treatment for hard-to-treat blood disorders, and advances in stem cell technology and transplant strategies. For the complete annual meeting program and abstracts, visit www.hematology.org/2012abstracts. Follow ASH (@ASH_hematology) on Twitter (use the hashtag #ASH12 when posting tweets about the meeting) and on Facebook at www.facebook.com/AmericanSocietyofHematology for the most up-to-date information about the 2012 ASH Annual Meeting.

The American Society of Hematology (ASH) (www.hematology.org) is the world's largest professional society of hematologists dedicated to furthering the understanding, diagnosis, treatment, and prevention of disorders affecting the blood. For more than 50 years, the Society has led the development of hematology as a discipline by promoting research, patient care, education, training, and advocacy in hematology. The official journal of ASH is Blood (www.bloodjournal.org), the most cited peer-reviewed publication in the field, which is available weekly in print and online.

[1] National Cancer Institute, "SEER Stat Fact Sheets: Chronic Lymphocytic Leukemia," http://seer.cancer.gov/statfacts/html/clyl.html (Accessed October 2012).

[2] Gribben, J.G., "How I treat CLL up front," Blood 115, no. 2 (2009): 187-197.

SOURCE American Society of Hematology

More Stories By PR Newswire

Copyright © 2007 PR Newswire. All rights reserved. Republication or redistribution of PRNewswire content is expressly prohibited without the prior written consent of PRNewswire. PRNewswire shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon.

Latest Stories
Why do your mobile transformations need to happen today? Mobile is the strategy that enterprise transformation centers on to drive customer engagement. In his general session at @ThingsExpo, Roger Woods, Director, Mobile Product & Strategy – Adobe Marketing Cloud, covered key IoT and mobile trends that are forcing mobile transformation, key components of a solid mobile strategy and explored how brands are effectively driving mobile change throughout the enterprise.
Pulzze Systems was happy to participate in such a premier event and thankful to be receiving the winning investment and global network support from G-Startup Worldwide. It is an exciting time for Pulzze to showcase the effectiveness of innovative technologies and enable them to make the world smarter and better. The reputable contest is held to identify promising startups around the globe that are assured to change the world through their innovative products and disruptive technologies. There w...
SYS-CON Events announced today that Pulzze Systems will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Pulzze Systems, Inc. provides infrastructure products for the Internet of Things to enable any connected device and system to carry out matched operations without programming. For more information, visit http://www.pulzzesystems.com.
Data is the fuel that drives the machine learning algorithmic engines and ultimately provides the business value. In his session at Cloud Expo, Ed Featherston, a director and senior enterprise architect at Collaborative Consulting, will discuss the key considerations around quality, volume, timeliness, and pedigree that must be dealt with in order to properly fuel that engine.
19th Cloud Expo, taking place November 1-3, 2016, at the Santa Clara Convention Center in Santa Clara, CA, will feature technical sessions from a rock star conference faculty and the leading industry players in the world. Cloud computing is now being embraced by a majority of enterprises of all sizes. Yesterday's debate about public vs. private has transformed into the reality of hybrid cloud: a recent survey shows that 74% of enterprises have a hybrid cloud strategy. Meanwhile, 94% of enterpri...
SYS-CON Events announced today that Hitrons Solutions will exhibit at the 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Hitrons Solutions Inc. is distributor in the North American market for unique products and services of small and medium-size businesses, including cloud services and solutions, SEO marketing platforms, and mobile applications.
SYS-CON Events announced today that Adobe has been named “Bronze Sponsor” of SYS-CON's 18th Cloud Expo, which will take place on June 7-9, 2016, at the Javits Center in New York, New York. Adobe is changing the world though digital experiences. Adobe helps customers develop and deliver high-impact experiences that differentiate brands, build loyalty, and drive revenue across every screen, including smartphones, computers, tablets and TVs. Adobe content solutions are used daily by millions of co...
Almost two-thirds of companies either have or soon will have IoT as the backbone of their business in 2016. However, IoT is far more complex than most firms expected. How can you not get trapped in the pitfalls? In his session at @ThingsExpo, Tony Shan, a renowned visionary and thought leader, will introduce a holistic method of IoTification, which is the process of IoTifying the existing technology and business models to adopt and leverage IoT. He will drill down to the components in this fra...
As the world moves toward more DevOps and Microservices, application deployment to the cloud ought to become a lot simpler. The Microservices architecture, which is the basis of many new age distributed systems such as OpenStack, NetFlix and so on, is at the heart of Cloud Foundry - a complete developer-oriented Platform as a Service (PaaS) that is IaaS agnostic and supports vCloud, OpenStack and AWS. Serverless computing is revolutionizing computing. In his session at 19th Cloud Expo, Raghav...
SYS-CON Events announced today that eCube Systems, a leading provider of middleware modernization, integration, and management solutions, will exhibit at @DevOpsSummit at 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. eCube Systems offers a family of middleware evolution products and services that maximize return on technology investment by leveraging existing technical equity to meet evolving business needs. ...
Data is an unusual currency; it is not restricted by the same transactional limitations as money or people. In fact, the more that you leverage your data across multiple business use cases, the more valuable it becomes to the organization. And the same can be said about the organization’s analytics. In his session at 19th Cloud Expo, Bill Schmarzo, CTO for the Big Data Practice at EMC, will introduce a methodology for capturing, enriching and sharing data (and analytics) across the organizati...
Enterprises have forever faced challenges surrounding the sharing of their intellectual property. Emerging cloud adoption has made it more compelling for enterprises to digitize their content, making them available over a wide variety of devices across the Internet. In his session at 19th Cloud Expo, Santosh Ahuja, Director of Architecture at Impiger Technologies, will introduce various mechanisms provided by cloud service providers today to manage and share digital content in a secure manner....
SYS-CON Events announced today that Isomorphic Software will exhibit at DevOps Summit at 19th International Cloud Expo, which will take place on November 1–3, 2016, at the Santa Clara Convention Center in Santa Clara, CA. Isomorphic Software provides the SmartClient HTML5/AJAX platform, the most advanced technology for building rich, cutting-edge enterprise web applications for desktop and mobile. SmartClient combines the productivity and performance of traditional desktop software with the simp...
With so much going on in this space you could be forgiven for thinking you were always working with yesterday’s technologies. So much change, so quickly. What do you do if you have to build a solution from the ground up that is expected to live in the field for at least 5-10 years? This is the challenge we faced when we looked to refresh our existing 10-year-old custom hardware stack to measure the fullness of trash cans and compactors.
The emerging Internet of Everything creates tremendous new opportunities for customer engagement and business model innovation. However, enterprises must overcome a number of critical challenges to bring these new solutions to market. In his session at @ThingsExpo, Michael Martin, CTO/CIO at nfrastructure, outlined these key challenges and recommended approaches for overcoming them to achieve speed and agility in the design, development and implementation of Internet of Everything solutions wi...