A rational
approach to
select centres to
decrease risks
and optimise
identification
of those patients
who will benefit
most from
immunotherapy
is required
in future
References
1 Mora J, Gerald M. The origin of
neuroblastic tumors: clues for
future therapeutics. Expert Rev
Mol Diagn 2004;4(3):293–302.
2 Marshall GM et al. The prenatal
origins of cancer. Nat Rev Cancer
2014;14(4):277–89.
3 Ries LAG et al. Cancer
incidence and survival among
children and adolescents: United
States SEER program 1975-1995.
Bethesda, MD: National Cancer
Institute.
4 Gatta G et al; RARECARE
Working Group. Embryonal
cancers in Europe. Eur J Cancer
2012;48(10):1425–33.
5 Maris JM. Recent advances in
neuroblastoma. N Engl J Med
2010;362:2202–11.
6 Mora J et al. Survival analysis of
clinical, pathologic and genetic
features in neuroblastoma
presenting as local-regional
disease. Cancer 2001;91:435–42.
7 Mora J et al. Gerald. Evolving
significance of prognostic
markers associated with
capillary leak syndrome. For all three studies, two
treatment-related deaths occurred due to capillary
leak syndrome and acute respiratory distress.
Toxicities were generally more frequent in
patients who received IL-2 compared with
patients who did not receive IL-2; in particular,
capillary leak syndrome, platelet abnormalities,
hypotension, infections, nausea or vomiting,
fever, and pain related to ch14.18/CHO.25 In the
continuous infusion studies APN311-202 and -303,
motor and sensory neuropathies were reported
with an incidence of 9% and 5%, respectively.
Regarding pain, the authors report that in the
continuous infusion studies, around 90% of the
patients experienced pain in cycle 1. The
percentage of patients with pain decreased in
subsequent treatment cycles, to about 60% in
cycle 5.
The Committee for Medicinal Products for
Human Use of the EMA recommended the
following indication for dinutuximab beta:
treatment of HR neuroblastoma in patients aged
12 months and above, who have previously
received induction chemotherapy and achieved at
least a partial response, followed by myeloablative
therapy and stem cell transplantation, as well as
patients with history of relapsed or refractory
neuroblastoma, with or without residual disease.
Before the treatment of relapsed neuroblastoma,
any actively progressing disease should be
stabilised by other suitable measures. In patients
with a history of relapsed/refractory disease and
in patients who have not achieved a complete
response after first line therapy, dinutuximab
beta should be combined with IL-2. These
indications are different from those for
dinutuximab, which includes only first-line
treatment.
Dinutuximab beta (Qarziba) is formulated as
a concentrate for solution comprising 4.5mg/ml
dinutuximab beta formulated with histidine,
sucrose, polysorbate 20, hydrochloric acid for
adjustment to pH 6.0, and water for injections.
To ensure an extractable volume of 4.5ml, the
vials are filled with 4.9ml of final product.
A solution of 0.9% sodium chloride containing
1% human albumin for dilution is used for the
preparation of the final solution for infusion.
The recommended posology consists of five
new treatmen