Chronic lymphocytic leukemia: New treatments coming

Cancer is (usually) caused by acquired genetic change.  Whenever a cell divides it must copy the roughly 6 billion nucleotides that make up our DNA.  Copying this DNA results in some mistakes and mistakes that occur in parts of the DNA controlling cell division or the death of cells results in uncontrolled cell division or failure of cells to die when they should.

Lymphocytes are always dividing, with new lymphocytes being formed to replace old ones that are no longer needed.  As new ones are formed it is important that the old ones die, or else lymphocytes will accumulate.

Chronic lymphocytic leukemia (CLL) is caused by a variety of acquired genetic changes.  Among the commonest are those that involve the BCL2 gene.  (BCL stands for B cell leukemia.)  The BCL2 gene product is a protein that interferes with cell death and the common change in this gene is over-expression.  Lymphocytes that over-express the BCL2 gene do not die when they should.

Drugs that interfere with the product of the BCL2 offer the potential to control CLL.  The New England Journal of Medicine (Roberts, A et al, January 28 2016, vol 374, No 4, p 311 report on a trial of venetoclax, an inhibitor of the BCL2 gene product.  One hundred and sixteen patients with relapsed CLL were treated and 79% of these patients enjoyed a response.  Side effects were tolerable and the commonest side effects were caused by the rapid death of leukemic cells. 

The same journal reported on another new drug for treatment of CLL, acalabrutinib.  This drug inhibits an enzyme called Bruton tyrosine kinase, an enzyme in the "B cell receptor signalling pathway" that leads to division of lymphocytes.  Inhibition of this enzyme is a proven treatment for CLL.  Acalabrutinib is a second generation bruton tyrosine kinase inhibitor that is expected to have fewer side effects than that first-in-class drug, ibrutinib.  Sixty-one patients with relapsed CLL received acalabrutinib resulting in a 95% response rate.

Neither acalabrutinib nor venetoclax are FDA approved yet.  Both drugs will need to undergo additional testing before submission for FDA approval.  However current treatments for CLL are quite effective and new treatments are on the horizon. 

These 2 drugs attack both of the problems that can cause cancer/leukemia: Failure of cells to die when they should (venetoclax) and excess cell division (acalabrutinib).  Advances in the molecular biology of cancer and development of treatments aimed at the abnormal genes causing cancers are among the most exciting developments in cancer research.  Most current cancer research is aimed at either this kind of drug or others that harness the power of the immune system. 

New treatment for myeloma: Elotuzumab (Empliciti)

Medical Oncologists have been steadily moving away from chemotherapy treatments for the last decade.  With rare exceptions, new cancer treatments are aimed either at specific gene products promoting growth of cancers or at enabling the immune system to fight the cancer.  Elotuzumab is an immunotherapy aimed at the CS1 molecule found on myeloma cells and "null killer" cells, or NK cells.

When elotuzumab binds to NK cells it activates them and when it binds to myeloma cells it identifies them for destruction by the immune system.

The first article on elotuzumab in our library at PCR Oncology is by A Jakubowiak et al in the Journal of Clinical Oncology Vol 30 No 16, June 1 2012.  This is a Phase I study of elotuzumab in 28 patients with relapsed myeloma, who were treated with escalating doses of elotuzumab in combination with bortezomib (Velcade).  About half of patients responded and side effects were tolerable.

The second article on elotuzumab in our library is by S Lonial et al in the New England Journal of Medicine, volume 373, No 7, August 13, 2015.  This paper describes the treatment of 646 patients with relapsed myeloma, who were treated with lenalidomide and dexamethasone with or without elotuzumab.  The response rate in the elotuzumab group was 79% (compared with 66% without elotuzumab).  Side effects were mild enough that elotuzumab did not interfere with quality of life.

The FDA approved elotuzumab for treatment of recurrent myeloma in combination with dexamethasone and lenalidomide on 11/30/15. 

We have now treated our first patient with this combination.  While it is too early to judge his response to treatment, we can say he, like those treated in the studies above, has not experienced significant side effects.

NCI Audit

All participants in human subjects research are subject to audits of quality of care and quality of research.  PCR Oncology underwent an audit by the National Cancer Institute in August of 2015. At the time of this audit the quality of care and research provided by PCR Oncology were reviewed by representatives of the National Cancer Institute.  We are proud to report that no recommendations for any change were made as a result of this audit.

Cancer Care and the Affordable Care Act

Despite the political rhetoric and controversy, there are some  benefits to patients that can be anticipated with the passage of the Affordable Care Act of 2010; AKA ObamaCare.  The new legislation provides patients with the security of not being denied insurance coverage for a past or current cancer diagnosis.  It  removes the barrier to participation into clinical trials posed by some insurance providers, and it allows adult children, to the age of 26, to remain on a parents insurance plan. It is also theorized to provide low cost insurance plans from a state exchange program to cover standard care.