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The World’s Leading Authority for Chronic Lymphocytic Leukemia Patients

ASH 2014: Dr. Jan Burger on Ibrutinib Resistance in CLL

Dr. Jan Burger from the MD Anderson Cancer Center spoke to me about his research on ibrutinib resistance in chronic lymphocytic leukemia at the ASH (American Society of Hematology) Annual Meeting in December 7, 2014.

TAKE AWAY POINTS:

  • The number of patients with resistance to ibrutinib is small, but is likely to grow as more and more high-risk patients are treated with ibrutinib for longer periods of time.
  • Mutations in the BTK pathway are a factor in ibrutinib resistance.
  • It appears that these mutations are present in very small numbers before treatment even begins and are selected out by therapy.
  • Risk factors for developing resistance including 17p deletion and especially in the presence of a complex karyotype, defined as the presence of three or more chromosomal abnormalities.
  • For patients who develop resistance, treatment options include bone marrow transplant, clinical trials, HDMP (high dose methylprednisolone) and a monoclonal antibody such as rituximab, or idelalisib.
  • We don’t know yet know what to do for a patient whose CLL is controlled but the disease is still present at low levels.

PREFACE:

Hematology in general and CLL specifically are full of jargon and acronyms that can be both overwhelming and daunting.  With time and experience, you’ll become familiar with the terminology and acronyms.  We will try to explain each medical term the first time it appears in an article, but we will use the true terminology so that you gain comfort and familiarity with the medical terms that you will see in your lab reports and in medical articles. We will also provide a glossary and a list of abbreviations and acronyms for your reference.

ASH 2014:

Dr. Burger’s working hypothesis about ibrutinib resistance is that a small population of cancer cells, maybe as few as a hundred, may be the pre-treatment nidus of a resistant clone that, with the selective pressure of treatment, can grow, become predominant and can eventually lead to a relapse.

These cells that cause the problems down the line tend to be the one that have the least genomic stability, those with deletion 17p or those with a complex karyotype. These two bad players tend to run together, so it can be hard to pin the blame on one more than the other, but this ASH abstract argues that the latter is more important.

Listen to Dr. Burger on the increasingly important topic of ibrutinib resistance.

 

Brian Koffman 5/10/15