NCCN Guidelines for Patients
Acute Lymphoblastic Leukemia, Version 1.2017
Targeted therapy is treatment with drugs that target
a specific or unique feature of cancer cells. Because
these drugs specifically target cancer cells, they may
be less likely to harm normal cells throughout your
body. The targeted therapy drugs that are used for
ALL are listed in
and are described next.
Guide 5. Targeted therapy drugs for
Generic name Brand name
Type of drug
Tyrosine kinase inhibitors
nhibitor) therapy is a type of
targeted therapy. TKIs are used for a subtype of ALL
in which the leukemia cells have the Philadelphia
chromosome. This subtype is called Ph-positive ALL.
The Philadelphia chromosome contains the abnormal
TKIs target the abnormal BCR-ABL protein that
helps leukemia cells grow. This protein is made by
gene. It is a type of protein called a
tyrosine kinase. TKIs block (inhibit) the BCR-ABL
protein from sending the signals that cause too many
leukemia cells to form.
TKIs are made in the form of a pill that is
swallowed. TKIs are typically not used alone to
treat ALL. Instead, a TKI is added to a combination
chemotherapy regimen. The use of TKIs has greatly
improved treatment outcomes for this type of ALL.
TKI drug resistance
A treatment response is an improvement in disease
that is caused by treatment. Drug resistance is when
ALL doesn’t respond to a drug. There is more than
one type of drug resistance.
Primary resistance is when ALL doesn’t respond
at all to a drug taken for the first time. This type of
resistance is rare in ALL. Secondary resistance is
more common. It is when ALL responds to a drug at
first and then stops responding over time.
A number of factors may cause or lead to secondary
resistance. Most often, it is caused by mutations
in the part of the
gene that makes the
BCR-ABL protein. These mutations change the
shape of the BCR-ABL protein. This can affect how
well certain TKIs work. New mutations can happen
over time during TKI therapy. This can cause the TKI
to stop working.
But, each TKI drug works in a slightly different
way. One TKI drug may be able to work against a
mutation that another TKI can’t. Therefore, switching
to a different TKI may result in a treatment response
after a prior TKI stops working.