The Latest News from CLL Global Research Foundation

Bits and Pieces from the CLL Global Community

Summer 2019

It is hard to believe we are already over halfway through the year. My how time flies when you are curing cancer! In this season's newsletter we'll bring you up to speed on what we've been been up to, from birthday celebrations and investigator-initiated clinical trials, to harnessing the immune system to fight cancer. It has been a banner year so far. 

Very exciting news on the use of targeted therapy in high-risk CLL patients was recently published by Jain et al. in The New England Journal of Medicine.The authors, which include several CLL Global grant awardees, report on an investigator-initiated phase 2 study combining ibrutinib and venetoclax therapy in previously untreated, high-risk and older patients with CLL. The results of the trial are impressive! After 12 cycles of the drug combination, all patients showed a response to treatment, with 88% of patients having a complete remission, and 61% of patients having remission with undetectable minimal residual disease. Further, there was no evidence of added toxicity when the two drugs were combined. Patients with undetectable minimal residual disease after 24 cycles of treatment will stop all therapy. Based on past studies with venetoclax, undetectable minimal residual disease should predict a long period of progression-free survival once treatment is discontinued. Having the ability to discontinue treatment for a period of time would lower the financial and side effect burdens for patients. We look forward to continued follow-up from this study to learn more about the long term efficacy of this targeted therapy. 
Happy Birthday, Dr. Keating and Dr. Wierda!
Dr. Michael Keating (right) and Dr. William Wierda
CLL Global would like to extend the warmest birthday wishes to our CEO and President, Dr. Michael Keating (July 1), and to CLL Global director and physician-extraordinaire, Dr. William Wierda (July 4). We feted the birthday boys with Tex-Mex and chocolate cake, along with lots of stories from past adventures and plans for future fun. Please join us in celebrating these two extraordinary people whose professional work has changed the lives of thousands of patients, as well as those who love them. Put in perspective, these two have changed the course of history. We wish you both the best year yet! 
Research Highlights
Fighting the Enemy Within: Retraining the Immune System to Tackle CLL

We reached out to MD Anderson Assistant Professor and current CLL Global grantee, Dr. Sabrina MT Bertilaccio, to find out how she became interested in studying CLL, and how funding from CLL Global is allowing her to tackle the disease and improve patients' health and quality of life. 
  1. What type of research does your lab do?
SB reply: Chronic lymphocytic leukemia is a neoplasia characterized by the expansion of malignant cells in the blood and lymphoid tissues of patients. The uncontrolled growth of malignant cells is induced by several genetic events but also by survival signals coming from the non tumor cells of the environment ("the microenvironment") which surrounds and fuels the tumor. The microenvironment is populated by several cells of the immune system which does not work properly and, instead of recognizing enemies and cells that can harm patients, they help leukemia to growth and to become resistant to therapies.
My lab focus on innovative therapeutic strategies aimed at re-establish a proper line of defense inside patient body and to repair their immune system. By studying the molecular interactions between the leukemic cells and the non-malignant immune cells, our goal is to identify new molecules and design new agents able to re-empower patient immune system against leukemia.


2. What led you to be interested in CLL research?


SB reply: During my PhD I was examining the immune system of prostate cancer patients and my attention went on blood cancers and chronic lymphocytic leukemia when I realized that actually in this malignancies the enemy (the "tumor cell") is inside the immune system itself.
In other words, our natural and sophisticated army ("the immune system") develops an inside enemy (CLL) which turns front-line soldiers into the worst enemies too. I thought that my expertise and knowledge in solid tumor immunology could help in understanding immune cell defects in CLL patients and to find a way to give them back their "inside weapons" to fight leukemia.
3.  How has funding from CLL Global Research Foundation helped you pursue and achieve your research goals?

SB reply: Thanks to the CLL Global research Foundation we identified an agent, used so far only in solid tumors, which is able to kill CLL cells but also to re-educate several cell types of the immune system to recognize leukemia as enemy. This drug is called trabectedin and it was originally extracted by a sea squirt. We demonstrated in pre-clinical studies that at very low doses it has the ability to repair the immune system and to kill leukemic cells, even the most aggressive, currently resistant to novel inhibitors. Thanks to these results we designed a novel clinical trial for CLL patients refractory/intolerant to BTK inhibitors, which is now open for enrollment at MD Anderson Cancer Center.  


4. In your opinion, what will the next big advance for CLL patients be?


SB reply: My dream is not only to provide CLL patients with new drugs to fight even the most aggressive and still incurable form of the disease, but also to guarantee patients a good quality of life. The big advance for CLL patients would be to have back all their "natural" cell weapons against leukemia, in absence of dangerous side effects.
CLL News
  • On May 15, 2019, the Food and Drug Administration ( FDA) approved combination venetoclax and obinutuzumab for initial treatment of patients with CLL. This marks the second chemotherapy-free treatment option approved for patients, the first being ibrutinib. The combination reduced the risk of disease progression and death by 67% compared with obinutuzumab/chlorambucil, and also had a higher rate of minimal residual disease negativity. 
  • Published in the Journal of Clinical Oncology this July, results form the phase II CLARITY trial looking at the use of ibrutinib and venetoclax in the relapsed and refractory CLL setting are encouraging. The combination was well tolerated and showed a high rate of minimal residual disease eradication, allowing some patients to stop all treatment after 12 months of combined therapy. 
  • Results from Shanafelt et al., published this month in The New England Journal of Medicine, indicate that treatment with ibrutinib + rituximab is superior to standard chemoimmunotherapy in patients with previously untreated CLL. At a medium followup of 33.6 months, the phase 3 trial involving 529 patients showed favorable progression-free (89.4% versus 72.9%) and overall (98.8% versus 91.5%)  survival in the ibrutinib + rituximab treated patients as compared to the chemoimmunotherapy group. According to Dr. Shanafelt, these results are likely to "dethrone FCR as the most active chemoimmunotherapy regime against CLL."
Sun Safety
Just because we're past the summer solstice doesn't mean it is time to slack off on using sunscreen. Patients with CLL have a compromised immune system which leads to an increased incidence in the development of other cancers (OC) , as compared to the general population, occurring at a frequency as high as 35% of patients. Skin cancer is the most common OC diagnosed in CLL patients, making year-round sun protection and skin cancer prevention a top priority. It is recommended that CLL patients have a yearly skin exam performed by a physician, and practice sun safety whenever they are outdoors. Outdoor sun safety measures includes using and reapplying sunscreen ( > SPF40), wearing a hat and sunglasses, wearing skin protective clothing, and seeking shade whenever possible. Also important for CLL patients to prevent, or catch at the earliest possible stage, OC is to stay on top of recommended cancer screenings and immunizations including the flu, pneumonia, and shingles vaccines. 
Featured Videos
Venetoclax plus obinutuzumab improves PFS and MRD-negativity in patients with previously untreated CLL and comorbidities
Venetoclax plus obinutuzumab improves PFS and MRD-negativity in patients with previously untreated CLL and comorbidities

Update on BTK inhibitors: Ibrutinib pus the new kids on the block: Are they better?
Update on BTK inhibitors: Ibrutinib plus the new kids on the block: Are they better?

 Thank you, Dr. Keating!
As many of you may know, our fearless leader, Dr. Michael Keating, has not been seeing patients in the Leukemia Clinic this year. After more than 50 years of uninterrupted patient care, and at the young age of 76, Dr. Keat ing has decided to take a sabbatical from direct patient care and instead focus on his research interests and, of course, CLL Global. "Just because I am taking a break from patient care doesn't mean I am taking a break from caring about patients!" Currently, Dr. Keating is working to expand our global outreach by supporting fellowships for trainees and visiting scientists from around the world, and of course he continues to support our amazing team of grantees and the incredible work they do. "We've made such great progress over the past decade, but there is still so much more we can achieve if we just put our minds to it. I plan to do just that." 
Reaching for a Cure
CLL Global has ambitious plans to further accelerate the scope and pace of CLL research, from the classroom, to the the lab, and into the clinic. From supporting training scholarships for fellows from around the world, to helping established standardized cancer screening and prevention guidelines for CLL patients, and sponsoring cutting-edge clinical trials that are changing the standard of care for patients with CLL, CLL Global is committed to improving the short- and long-term survival outcomes and quality of life for patients, their caregivers, and loved ones. All we have accomplished, and all we will accomplish, is thanks to our incredible family of benefactors who support us with their spirit, time, and money. Thank you for all you do! 


CLL Global Research Foundation
Newly Diagnosed

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

(Provided by ACOR)
CLL Global Research Foundation
PO Box 301402, Unit 428 | Houston, TX  77230