The first results of the CeGAL * clinical trial:
a promising approach in acute myeloid leukemia (AML)
Marseille, July 2, 2020.
A collaboration between clinicians and pharmacology researchers from the Paoli-Calmettes Institute
(IPC) and the CRCM (Center for Cancer Research of Marseille) produced the
first results of the CeGAL personalized medicine clinical trial in onco-hematology.
These results have been published in the Blood Cancer Journal.
Moving from the era of therapy adapted to the greatest number to that of so-called precision medicine
in which each patient would benefit from individualized treatment guided by
molecular characterization of their tumor, this is the paradigm shift in medicine.
Pr Norbert Vey’s team completed the genomic data characterizing a tumor
by functional tests to identify its Achilles heels. The advantage of this approach is
particularly marked in acute myeloid leukemia (AML) for which the majority of patients
relapse and succumb to the disease with an overall 5-year survival rate of around 20%. In
coordination with Dr Daniel Birnbaum’s Predictive Oncology team and the TrGET preclinical platform
led by Dr Yves Collette, sensitivity and resistance profiles to a panel of drugs
(authorized for medical use, or during clinical investigation) were performed ex
in vivo on leukemia cells from refractory patients or patients who have relapsed from their treatment;
in parallel the tumor was genomically characterized.
“By focusing specifically on this population of refractory patients recruited within the frame of a
formal clinical trial promoted by Paoli-Calmettes Institute, we have assessed the feasibility of
producing relevant genomic and functional data which are discussed by a committee in real time in order to orient the therapeutic strategy chosen by the clinician ”,
Dr Aude Collignon, first author of the publication, explains.
The main objective of this study was achieved for 58% of the patients, 35% of whom received the treatment
guided by the TTS (Tailored Treatment Strategy). Fifteen of these seventeen TTSs were guided by
combined genomics and drug susceptibility data, while two TTS were guided
by genomics or drug sensitivity data only.
These results show that chemogenomics combining of the characterization of genomic alterations
and drug susceptibility testing to determine a TTD is a workable and promising approach
to provide patient-specific treatment options within 21 days. The short
overall survival time (≈ 3 months) in this cohort favors the inclusion of patients earlier in their
therapeutic course, supported by 4 complete responses in the TTS group.
In oncology, the pan-genomic high-speed technology revolution and now analyzes at
the single cell level have allowed considerable progress, notably by the identification of signatures
molecular characteristics of subgroups of patients with variable prognostic values. These analyses
also reveal the full scale of cancer heterogeneity and the complexity of cancer treatment. The
chemogenomics adapted to real-time management of patients allows this
complex mapping of the tumor cell, providing clinicians with possible treatment options,
in particular for refractory patients or patients relapsing from their treatment.
The extension of this study to an increasing number of patients and their comparative chemogenomic analysis
with patients at the time of diagnosis is underway, which should allow better identification and
target the specifics of these refractory patients while improving their personalized care.
Reference: Collignon, A., Hospital, M. A., Montersino, C., Courtier, F., Charbonnier, A., Saillard, C., D’Incan, E., Mohty, B.,
Guille, A., Adelaïde, J., Carbuccia, N., Garnier, S., Mozziconacci, M. J., Zemmour, C., Pakradouni, J., Restouin,
A., Castellano, R., Chaffanet, M., Birnbaum, D., Collette, Y., … Vey, N. (2020). A chemogenomic approach to
identify personalized therapy for patients with relapse or refractory acute myeloid leukemia: results of a prospective
feasibility study. Blood cancer journal, 10(6), 64. https://doi.org/10.1038/s41408-020-0330-5