Leukemia Drug Imbruvica

Imbruvica will help some with relapsed or refractory leukemia


Imbruvica (ibrutinib) is a paradigm-shifting drug which represents a sea change in how we treat chronic lymphocytic leukemia (CLL) and other B-cell malignancies. More specifically, Imbruvica shifts leukemia treatment away from buckshot chemotherapy clumsiness to sniper-like enzymatic finesse.

What is CLL?

Chronic lymphocytic leukemia (CLL) is the most common adult leukemia in Western nations. (The disease mostly affects whites and fells far fewer African Americans, Hispanic people and Asians.) This disease is most prevalent in older people with a median age of diagnosis of 72.

Chronic lymphocytic leukemia is a cancer of B lymphocytes which normally confer humoral immunity and serve as an integral component of our immune system.

With CLL, a preponderance of leukemic B lymphocytes accumulate and crowd out normal blood cells in the bone marrow, blood and lymph nodes. With a dearth of blood cells that our body needs like red blood cells and white blood cells, CLL can respectively cripple our ability to fight infection and cause anemia.

Prognosis for people with CLL runs the gamut. Some people are lucky and live for decades with indolent or low-key disease which requires no treatment. Others, however, suffer a much more dangerous course that is resistant to chemotherapy.

Typical symptoms in those who suffer rapidly progressive CLL include the following:

  • fatigue
  • weight loss
  • fever
  • night sweats
  • enlarged lymph nodes
  • enlarged spleen or liver contributing to early satiety (early feeling of fullness)
  • recurrent infection

In 2015, the National Cancer Institute estimated that of the 14620 cases of CLL diagnosed, there were 4650 deaths.

What's so special about Imbruvica?

Until recently, treatment of CLL was limited to chemotherapy combined with immunotherapy or chemoimmunotherapy. Although chemotherapy by itself is merely palliative for some of those with CLL, the more recent addition of rituximab, an immunotherapy drug, can help prolong survival by inducing remission.

More specifically, rituximab targets the CD20 antigen on B lymphocytes. Unfortunately, a certain subset of people (those with del[17p]/TP53 mutations or deletion in chromosome 17) respond poorly to chemoimmunotherapy.

Chemotherapy for CLL involves the parenteral administration (injection) of various agents in order to kill off not only rapidly dividing cell lines but also normally dividing cell lines, too. This buckshot approach explains why people on chemo suffer a variety of adverse effects including hair loss, gastrointestinal distress, and, in the case of CLL, even more myelosuppression or humoral effects.

Whereas chemo accords the clinical accuracy of a chain saw--or, for all you Walking Dead fan's out there, Negan's weapon of choice, Lucille--Imbruvica is like a surgeon's scalpel and precise in its mechanism. Specifically, Imbruvica knocks out an enzyme called Bruton's tyrosine kinase (Btk) distinct to malignant or leukemic B cells. By irreversibly binding to Btk, Imbruvica throws a monkey wrench in the chronically active B cell receptor pathway thus inhibiting cell growth, proliferation, and survival of malignant B cells.

(I just realized that the abbreviation Btk is similar to serial killer Dennis Rader's BTK moniker ... an unfortunate coincidence no doubt.)

Interestingly, researchers suggest that Imbruvica may function by another related mechanism which involves screwing up the microenvironment in which leukemic cells proliferate. Specifically, and as detailed in the journal Nature Biotechnology, Imbruvica may "block chemokine receptor and integrin signaling by inhibiting BTK, and therefore cell migration and adhesion to the stromal cells in the lymph node. After Imbruvica administration, CLL cells increase in blood and may die there, deprived of the supportive microenvironment provided by the lymph node."

Besides CLL, Imbruvica also helps with a variety of other B-cell malignancies. Consequently, in addition to CLL, the FDA has issued the drug fast-tracked or breakthrough therapy designation for Waldenström’s macroglobulinemia and mantle cell lymphoma. No other drug has received this many breakthrough therapy designations!

If you or a loved one suffers from CLL or another B-cell malignancy, Imbruvica's debut is definitely something to be excited about. With respect to blood-borne malignancy, Imbruvica's anticipated success can only be compared with rituximab. Furthermore, Imbruvica is not only more effective than rituximab as monotherapy but also orally administered and useful with refractory and relapsed disease.

Selected Sources

Article titled "Imbruvica—next big drug in B-cell cancer—approved by FDA" by Malini Guha published in Nature Biotechnology in 2014. Accessed on 2/26/2015.

Article titled "Ibrutinib (Imbruvica): A Novel Targeted Therapy for Chronic Lymphocytic Leukemia" by S Parmar and co-authors published in P&T in 2014. Accessed on 2/26/2015.

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