Improvements in outcome for pediatric hematological malignancies have mainly been driven
by the optimization of multi-agent chemotherapy regimens, minimal residual disease
monitoring, and risk group stratification based on (cyto)genetic prognostic markers. The
prognosis after (multiple) relapse(s) or other new relapsed/refractory (r/r) entities,
such as relapse post CAR T-cell therapy in B-cell precursor acute lymphoblastic leukemia
(BCP-ALL) and persistent MRD after reinduction therapy for relapsed T-cell ALL, remains
poor. This is due to the lack of effective salvage therapies. The options for salvage
therapies also differ per disease type: limited options exist in r/r acute myeloid
leukemia (AML), T-cell acute lymphoid leukemia and lymphoblastic lymphomas (LBL) compared
to r/r BCP-ALL. Recently, new ALL relapse categories have been identified for which an
umbrella clinical trial is in development with a molecularly stratified approach: the
HEM-iSMART protocol. These new categories consist of multiple relapsed BCP-ALL post CART
(which frequently means also post-SCT), and T-ALL/LBL which fail reinduction therapy at
first relapse. For AML, early phase clinical studies are set up in the context of the
so-called PedAL initiative. Typically second or greater relapsed AML is considered an
experimental indication.
Molecular profiling of leukemias and lymphomas is performed in many European countries
and the results and potential treatment options are discussed in tumor boards of the
national groups. However, numbers in each of these national initiatives are limited,
especially when focusing on the new ALL relapse categories, whereas the type of
actionable events can be numerous and different between disease types.
The international Leukemia Target Board (iLTB) is fostered by the International
Berlin-Frankfurt-Muenster (I-BFM) Resistant Disease and AML committees, the European
Inter-group for Childhood Non-Hodgkin Lymphoma (EICNHL) and the ITCC (Innovative
Therapies for Children with Cancer in Europe), and has been initiated to discuss these
national profiling results with experts from diverse disciplines at a European level,
with the aim to better understand the nature of these relapses and to facilitate entry in
early phase clinical trials. This will ensure that, as patients are scattered across
countries, treating physicians receive the best advice about the prioritization of
potential treatment options and open trials according to the patient's actionable events
prioritization and treatment history when confronted with these specific relapse
situations.
Different from (inter)national tumor boards focused on solid tumors, in addition to the
discussion of molecular lesions at the DNA/RNA level, the iLTB will discuss
immunophenotypic (CD markers)/surface antigen information and if available centralized
drug response profiles (DRP) of r/r hemato-oncology patients for whom standard options
for cure are very limited. The available information will be integrated by a newly
developed prioritization algorithm that has been developed by an international iLTB
development team and which will be optimized prospectively. An actionable event is
defined in this study as a tumor characteristic for which targeted therapy is approved,
or investigated in a clinical trial for any cancer indication, including but not limited
to small molecules and immunotherapy.
It is hypothesized that an international platform for discussing the clinical and
biological as-pects of children, adolescents, and young adults with relapsed and
refractory hematological malignancies to decide the most appropriate treatment for each
individual patient can be a way forward to uniform the community and to tackle these
challenges.
The ultimate aim of the iLTB is to improve the outcome of patients with r/r hematological
malignancies as defined above by prioritizing actionable lesions in a uniform setting
through a panel of experts which advises treating physicians about matching trial(s) or
the most appropriate alternative when access to a clinical trial is not possible.
The investigators would like to stress that the iLTB is a platform which is meant to
timely share, harmonize, and unify the knowledge about actionable lesions and treatment
options for only a subset of r/r cases in Europe, i.e., the patients where the national
group asks for discussion in the iLTB, and as such the iLTB does not intend to interfere
with outcome evaluations linked to national/local tumor board initiatives.
Enrollment of patients will be coordinated by a representative from the national
coordinating center (NCC). Informed consent from the patient to share the data in the
iLTB is the responsibility of the treating physician/NCC and is needed prior to
discussing the patient's data. Results will be fed back to the treating physician via the
NCC or directly.
Treatment interventions however, are not part of this study protocol. Any treatment as a
result of iLTB advice will be proposed to the patient by the treating physician and will
be subject to a separate consent procedure.
