on clinical trial results showing that adding dinutuximab
and two immune system–boosting agents—
granulocyte-macrophage colony-stimulating factor and interleukin- 2
(see sidebar on How Immunotherapeutics Work, p. 83)—to
standard 13-cis-retinoic acid (RA) treatment significantly
extended overall survival (143).
Children like Elizabeth Buell-Fleming (see p. 90) have
benefited from dinutuximab; however, treatment with this
immunotherapeutic is associated with significant toxicities.
These toxicities can be so severe that some children do not
complete the course of treatment. Consequently, researchers
are looking to identify ways to pinpoint more precisely
those children most likely to benefit from dinutuximab, so
that those unlikely to respond can be spared the potential
adverse effects of this treatment.
Because of the effectiveness and promise of antibody-based
immunotherapeutics, many researchers have been working
to develop both new as well as improved versions of this
important class of anticancer therapeutics.
One such therapeutic is the first of a new class of antibody-based immunotherapeutics called bispecific T cell–engager
(Bi TE) antibodies, blinatumomab (Blincyto) was approved
by the FDA in December 2014 for treating certain patients
with a type of ALL called B-cell ALL.
Bi TE antibodies function as a connector, bringing T cells
into close proximity with cancer cells, which are then
eliminated by the T cells. Blinatumomab attaches to a
molecule called CD3 on T cells and to CD19, a molecule
found on the surface of most B-cell ALL cells. By attaching
to these molecules on the different cells, blinatumomab
brings the two cell types together, directing the T cells to
home in on the B-cell ALL cells.
The approval of blinatumomab for treating adults who
have precursor B-cell ALL that has progressed despite a
prior form of treatment and that has a molecular profile
characteristic of poor outcomes (it lacks the Philadelphia
chromosome) was based on results from a clinical trial
showing that the novel immunotherapeutic was effective
in more than 30 percent of patients (145). Historically,
precursor B-cell ALL that has progressed following initial
treatment has been extremely challenging to treat. In fact,
even with intensive therapy, the median survival is between
three and six months. Thus, the approval of blinatumomab
provides patients like Sergio Ramirez (see p. 92) with new
treatment options and new hope.
Living With or Beyond Cancer
Research is powering advances in cancer detection, diagnosis,
and treatment that are helping more and more people to
survive longer and lead fuller lives after a cancer diagnosis.
According to the latest estimates, almost 14. 5 million U.S.
residents with a history of cancer were alive on Jan. 1, 2014,
compared with just 3 million in 1971, and this number is
projected to rise to 19 million on Jan. 1, 2024 ( 3, 5). About 3
percent of these individuals, including Jay Steiner (see p. 96),
are proteins that have a
therapeutic effect when they
attach to a specific molecule in
the body. They are effective in the
treatment of numerous cancer
types and function in several
about 710 U.S. children are
diagnosed with neuroblastoma
each year, making it the third most
common childhood cancer (144).
about half of neuroblastoma
cases are classified as
high-risk disease (143).
among children with high-risk
neuroblastoma, the five-year
survival rate is about 40 - 50%,
even with aggressive therapy.