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If you have recently been diagnosed with CLL, you probably have questions. 


Information about CLL


What we are doing to defeat CLL


Patient Power's Andrew Schorr interviewed leading scientists about popular topics in CLL research at the ASH meeting.

New T-cell
New T-cell "CAR" Research for CLL

Results Suggest a Potential Breakthrough in CLL
Ibrutinib Results Suggest a Potential Breakthrough in CLL

New Horizon in Oral Medication for Blood Cancer Treatment
New Horizon in Oral Medication for Blood Cancer Treatment

 human testing tshirt


 Click on the links to view details of other clinical trials for ibrutinib:


Ibrutinib in Combination with Bendamustine and Rituximab for Relapsed or Refractory CLL/SLL 




Ibrutinib for 17p- Patients with Relapsed or Refractory CLL/SLL 




Ibrutinib versus Chlorambucil in Treatment-naive  Patients 65 or Older with CLL/SLL  


Chimeric antigen receptors (CARs)are a promising new therapy being tested in early phase trials. Initial results are so good they are making headlines in the news. 


CARs made the list of the biggest health stories of 2012 in the Huffington Post.

Click here to read article. 


CARs were also featured on local news stations. Below is an example from Utah.


Click here to read the article/watch the video. 



The goal of stem cell transplantation is to replace unhealthy immune cells with healthy ones that can recognize and kill cancer cells. It can be difficult to find a donor that is a match, but the use of cord blood can increase success rates. Dr. Elizabeth Shpall and colleagues at MD Anderson Cancer Center have found a way to better utilize these cells. 


Click here to learn more. 



You may have to scroll through each newsletter to find the article.

Articles are listed from most recent to oldest.

Effects of CLL
The Development of CLL


Immune Cells


Do you have questions about the immune system or CLL?
Email us and we will provide answers to your questions as the series continues.


There is a wealth of information in previous issues of both Tidbits and CLL Research Momentum.
Click here to view the newsletter archives page.


Is there something specific you want to read and learn about? 


Let us know if you have any comments or suggestions for improvement.


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January 2013


Welcome to 2013! New CLL treatments were a major topic of discussion at the ASH meeting in December. Highlights are below. Also learn about a new clinical trial for ibrutinib and antibodies in CLL. Let's get to it. 


ASH 2012


Image obtained from www.hematology.org.

Before 2012 becomes a memory, we want to look back at the highlights of the 2012 ASH Annual Meeting. The American Society of Hematology meeting takes place each December. Researchers from around the world are invited to present their latest research on blood diseases and disorders. A copious amount of information and accomplishments were presented on CLL.


Trial results on the kinase inhibitor, ibrutinib, and CARs dominated the CLL scene. You can catch a glimpse of the excitement by watching the videos in the side bar to the left. Other topics were also discussed at ASH; they may not have received as much media attention but are important pieces in the quest to cure CLL.


Data was presented on several new treatments that target specific molecules. Multiple drugs are being tested that target bcl-2, an important molecule that prevents CLL cells from dying. ABT-199 is being tested in phase I trials, and ABT-263 has been compared to and combined with rituximab in a phase II trial. Both drugs are effective but come with side effects. ABT-263 appears to increase responses when combined with rituximab even in 17p- patients (generally an indicator of poor response to treatment).


Researchers from Sweden and Iran presented laboratory results on a monoclonal antibody which targets ROR1, a protein overexpressed on CLL cells but not found on normal B-cells. In the studies, the anti-ROR1 antibody deactivated signaling proteins involved in CLL cell survival and caused CLL cells to die. Based on information gathered, additional studies are needed to better understand signaling pathways associated with ROR1.


Signaling molecules are critical for CLL cells to communicate with other cells and to survive. Some of these molecules are the targets for the drugs mentioned above. However, there are hundreds of potential targets. Researchers continue to analyze all of the molecules and pathways they can find to fully grasp the complex interactions. There were several ASH presentations on new molecules and their potential role in CLL development. 


Some researchers are going beyond molecules and signals and into the depths of the genes that determine the makeup of the cell. Gene mutations are providing huge insight into the diversity of CLL.


NOTCH1 is a newly discovered gene in CLL cells which occurs in approximately 10% of patients. According to data from a study conducted in Germany, patients with a NOTCH1 mutation did not benefit from the addition of rituximab to the fludarabine and cyclophosphamide (FC) regimen. Surprisingly, a small portion of patients with the 13q- on FISH, which is the most favorable prognostic factor, had mutations of a new gene, SF3B1, which is associated with a poor outcome.    


These and other newly discovered genes will continue to be analyzed against established prognostic markers. The goal is to know how every patient's disease will respond to treatment and to more effectively decipher the most optimal treatment for each patient.


Ibrutinib Versus Ofatumumab


The buzz word these days is ibrutinib because of the dramatic results of Phase I and II clinical trials recently presented at ASH. It is being put up to a final test before being considered for approval by the FDA and international government agencies for the treatment of CLL.


CLL patients are currently enrolling in a Phase III clinical trial comparing ibrutinib to ofatumumab, a monoclonal antibody already approved for the treatment of CLL. The study, known as the RESONATE study, is open to patients who have relapsed or who have refractory CLL, including those with 17p- which is considered a poor prognostic marker.


Ibrutinib blocks the Bruton's tyrosine kinase (Btk) protein which is found on healthy B-cells and CLL cells. Btk functions normally in healthy B-cells, but not in CLL cells. It is part of a signaling pathway needed by CLL cells for growth and survival. Btk also helps keep CLL cells in the lymph nodes where they are better protected.


Blocking Btk liberates the CLL cells into the blood stream

where they slowly starve and are more susceptible to treatment. As a result, patients experience a significant reduction in lymph node size, and at the same time their white blood cell count spikes but eventually normalizes as the CLL cells die.   


Ofatumumab targets CD20 which is a molecule found on the surface of B-cells, including CLL cells. It was approved in 2010 for the treatment of CLL. Both ofatumumab and rituximab, another monoclonal antibody, target the CD20 molecule. Ofatumumab seems to be better at binding to CD20 than rituximab in CLL cells. It is also effective in patients who did not benefit from treatment with rituximab, making it a good comparator to ibrutinib. 


The primary goal of this Phase III trial is to see if there is a clinically significant improvement in progression-free survival when ibrutinib is compared to ofatumumab, an approved treatment option. It must be shown through trial results that ibrutinib is equally effective with fewer side effects or superior to standard therapy. These results will be used by the FDA when considering the approval of ibrutinib; FDA approval would make the treatment more widely available to CLL patients. FDA stamp   


The trial is currently open at more than 50 locations around the world and is accruing rapidly. It is a randomized trial which means the patient, the doctor and the drug company cannot choose which patient will go on which drug. To eliminate bias, a computer decides whether patients will go on the ibrutinib or ofatumumab arm. Randomized trials help demonstrate that a particular agent or regimen is beneficial on average to a large population of patients.


Additional ibrutinib trials are ongoing and others are planned. Ibrutinib has been beneficial for patients regardless of prognostic markers. One new study will specifically target patients with 17p- which are often difficult to treat. Other trials will combine ibrutinib with additional therapies for patients with relapsed or refractory CLL and there is also a trial planned comparing ibrutinib with chlorambucil as frontline therapy in elderly patients.


Phase III trial results will be reviewed by the FDA to make sure the treatment is safe and effective for use by all patients. If approved, ibrutinib will be available for CLL patients at doctors' offices worldwide. We will continue to provide updates on this Phase III trial and others as they become available.


Click here to read additional information about the trial from clinicaltrials.gov. 


As with any study, enrollment is limited and a patient must meet eligibility criteria. Consult with your physician to determine if a clinical trial is an appropriate avenue for treatment.



Immune System: Antibodies and IVIg


CLL cells are malignant immune cells; malignant B-cells to be exact. Over the last few months, we have been laying out the basics about the immune system and the effects of CLL on the immune system. Links to previous articles are in the side bar to the left.


Last month we left off talking about antibodies which are Y-shaped proteins produced by B-cells to fight harmful invaders called antigens. Because many CLL patients have a lower number of healthy B-cells, they also have a lower number of antibodies and are more prone to infections. 

Structure of antibody. Image obtained from www.unm.edu


There are five main types of antibodies with varying functions and locations in the body:


IgA - Found in tears, saliva and mucus. Defends at the surface of the body and is important in preventing respiratory infections.


IgD - Functions are still not fully understood, but may play a role in immune surveillance and immune activation.  


IgE - Triggers histamine release in response to allergens. This release is what causes side effects associated with allergies.


IgG- Most common and versatile. Capable of carrying out all antibody functions.


IgM - First antibody to respond to infections until there are sufficient levels of IgG.


(Ig stands for immunoglobulin, the scientific term for antibodies.)


Antibodies are under-produced in CLL patients, not only because there are fewer normal B-cells, but also because CLL cells actively impair the immune system. As we have discussed over the last several months, the human immune system is made up of an intricate network of cells and organs. Because of the importance of B-cells, this network becomes dysfunctional in many ways including an increase of infections.


Patients with a severe infection or frequent infections may be candidates for intravenous immunoglobulin (IVIg) therapy in which antibodies are isolated from the blood of healthy donors and given to patients through a transfusion. Antibodies from thousands of donors are pooled so that the recipient can fight an array of infections.


All antibodies do die off so multiple infusions may be necessary. For patients with little to no antibody production monthly IVIg infusions may be a long-term or permanent part of living with CLL. IVIg therapy only utilizes the IgG antibodies so only a portion of antibodies are being replaced. Patients may still have infections after receiving therapy.


Image obtained by



IVIg therapy has been around for 30 years and carries little risk. People do experience side effects like skin reactions, fever or joint pain but usually only after the first infusion. Adverse reactions are rare. CLL is on a very short list of indications approved by the FDA for IVIg therapy. Even so, it is not used unless absolutely necessary. IVIg therapy is very expensive, often not covered by insurance and not readily available. 


Currently IVIg therapy is the only FDA approved option to increase the effectiveness of immune systems in patients with CLL. IVIg does not reverse the negative effects of CLL on the immune system. It is usually a band-aid fix to a much bigger problem. Methods of improving immune system function are currently under investigation and will be the subject of discussion next month.


We have high expectations this year for treatment breakthroughs and discoveries. We look forward to keeping you up to date.



CLL Global Research Foundation