Finding Alternatives to Combination Therapy to Improve Quality of Life for Chronic Lymphocytic Leukemia Patients

Designed to Cure

leukemiaChronic lymphocytic leukemia is a devastating disease without a cure. By looking beyond classic combination therapy approaches, scientists are getting closer to a cure. Image Source: Flickr user euthman

Often, when we think about cancer treatment we immediately think of some generic form of chemotherapy or radiation, but there are many types of cancer that cannot be dealt with in this manner. Chronic Lymphocytic Leukemia (CLL) is not your stereotypical childhood leukemia. It is (currently) an incurable illness that is most commonly diagnosed in older adults. This cancer is not fast moving and may progress slowly enough that it can be monitored and go untreated for long stretches of time between therapy sessions. This can be considered preferable to some patients, since current cancer treatments are toxic and only offer the possibility of remission.

If the cancer is progressing quickly enough to merit full treatment, there are a number of go-to combination therapies that oncologists use first,1 including fludarabine-based therapy, pentostatin-based therapy, and bendamustine-based therapy. But while many of these treatments are quite effective, they are highly toxic and none provide a cure. They operate as band-aid solutions, allowing the patients to enter remission, only to have them relapse in the coming months or years.

Directed research needs to be conducted to better assess the reasons why these compounds work the way they do in combination with one another. Perhaps by paring down the number of medications taken, side effects can be mitigated. Additionally, it would be beneficial to gain a better grasp of why these combination therapies are so toxic for many patients. Yes, they are interfering with immune function and contain classic chemotherapeutic compounds, but why are these particular regimens so awful? Researchers would benefit from an innovative software platform to better target specific therapeutic sites and to weed out problematic compounds to avoid wasting precious R&D dollars.

Inhibitor Therapies Show Promise

Recently, a paper was published in the Lancet stating that a Ofatumamab-based consolidation therapy appears effective for CLL.2  This is exciting news for researchers, as it presents data showing that the majority of patients in the trial were able to go treatment-free for 18 months. These findings indicate that quality of life may increase and survival rates could be vastly improved.

Additionally, the FDA recently approved two new inhibitors for treatment of CLL: idealisib (a P13K inhibitor) and ibrutinib (a BTK inhibitor).3 Ibrutinib plays into personalized cancer treatment; it is far more effective in those without del17p/11q. Tracking little genetically-based efficacy nuances such as this would be made easy through the use of modern lab software. By better tracking genome differences in combination with efficacy trends, researchers may be able to bring treatments through to clinical trial more efficiently.

The prior inhibitor, idealisib, had incredibly promising results, but it is fraught with the horrid toxic effects seen in many of the combination therapies. Researchers are taking this opportunity to learn from the medication. Yes, it inhibits BTK, but it is also having effects on many other kinases, such as EGFR, ITK and TEC. Developers of the next generation of BTK inhibitors are taking this into account and narrowing the range of their targets. These drugs are still in development, and although they show the potential to be highly effective, toxicity has yet to be fully investigated. Scientists will have to find a way to better categorize the kinases at play and find new therapeutic targets. Modern lab software can assist scientists as they review copious amounts of data and better model the target, as well as how potential therapeutics may interact with the aforementioned newly discovered targets. This technology also has capabilities for assisting investigators in how to better deliver these medications through antibody-drug conjugate therapies. Within the realm of conjugate therapies, it has the ability to assist researchers through identification and design/refinement of antibody based therapies, which may be the key to success in these cancers.

Beyond the scope of CLL, both idealisib and ibrutinib have been approved by the FDA to be used in the treatment of multiple, hard-to-treat blood cancers.4 Like CLL, many other blood cancers have no cure, and lack good treatment options. The need is imminent for better treatment and understanding of these disorders is extremely important. New advances in lab software will be the key in developing better treatment. Scientists will be able to better design, track and assess the efficacy of these therapies across the board. Additionally, researchers may be able to move towards true cures rather than mere periods of remission.

Fortunately, BIOVIA Designed to Cure can assist in the design and tracking of therapeutics. The Designed to Cure industry solution experience delivers collaborative, knowledge-driven innovation and predictive analytics to address challenges, such as those associated with kinase inhibitors and the hosts of toxic side effects related to other current therapeutics. Please contact us today to learn more about how our software options can support the efforts of your lab.

  1. “Chronic Lymphocytic Leukemia Treatment Protocols,” March 11, 2016, http://emedicine.medscape.com/article/2005390-overview
  2.  “Ofatumumab monotherapy as a consolidation strategy in patients with previously untreated chronic lymphocytic leukaemia: a phase 2 trial,” August 1, 2016,  http://thelancet.com/journals/lanhae/article/PIIS2352-3026(16)30064-3/fulltext
  3. “The Changing Treatment Landscape of Chronic Lymphocytic Leukemia,” July 25, 2016, http://www.curetoday.com/articles/the-changing-treatment-landscape-of-chronic-lymphocytic-leukemia?p=1
  4. “Advance of the Year: Gains In The Treatment Of Chronic Lymphocytic Leukemia,” 2016, http://cancerprogress.net/cca/advance-year