Post on 28-Sep-2020
Focus sur les CAR-T cellsLes Ateliers de la Recherche Clinique – RRC OncoPaca-Corse
Mougins- 31/01/19
Pr Thomas Cluzeau
Université cote d’Azur
Service d’hématologie clinique, CHU de Nice
INSERM U1065, Centre méditerranéen de médecine moléculaire
CAR-T cells 1ère génération
CAR CAR + IL2
CAR-T cells 2ème génération
Hombach, Journal of Immunology 2001
Hombach, Journal of Immunology 2001
Hombach, Journal of Immunology 2001
ACE -
Hombach, Journal of Immunology 2001
ACE -
ACE+ / B7- ACE+ / B7+
Savolado, JCI 2011
CAR-T cells 3ème génération
Sadelain, Nat 2017
Sadelain, Nat 2017
Zhao Cancer Cell 2015
NALM6
Persistance
Zhao Cancer Cell 2015
NALM6
Persistance
Zhao Cancer Cell 2015
NALM6
Zhao Cancer Cell 2015
NALM6
Zhao Cancer Cell 2015
NALM6
Persistance
Zhao Cancer Cell 2015
NALM6
Persistance
Sadelain, Nat 2017
Sadelain, Nat 2017
CAR-T cells nième génération
CAR-T cells « actionnable »
Wu Science 2015
Juillerat Sci Reports 2015
CAR-T cells nième génération
CAR-T cells « universels »
Eyquem Nature 2017
CAR-T cells « en pratique »
Immunotherapy in cancer
1890 1957 1985 1997 20092010 2011 20141976
Treatment of
cancer with
bacterial
products
(“Coley’s
toxin”)
Cancer immuno-
surveillance
(Burnet,
Thomas)
BCG in
bladder
cancer
(1st study)
Adoptive
T-cell
therapy
1986
IFNa
approved
in
hairy cell
leukemia
Anti-CD20 mAb
(Rituximab)
approved
in NHL
1998
IL-2
Approved in
melanoma
HPV
vaccination
in vulvar
intraepitheli
al neoplasia
DC vaccine
(Sipuleucel-T)
approved in
prostate cancer
Anti-CTLA4 mAb
(ipilimumab)
approved in
melanoma
Anti-PD1 mAb
(pembrolizumab)
approved in
melanoma
2017
1st CAR-T
approved in
acute
lymphoblastic
leukemia
1950
Allogeneic
Stem-cell
transplantatio
n
Davila, Oncoimmunology. 2012 Dec 1;1(9):1577-1583
ELIANA-CTL019 global trial: R/R BCP-ALL
Eligibility criteria
Inclusion : R/R BCP-ALL, age 3-21 years, ≥ 5% BM blasts
Exclusion : isolated extra-medullary relapse, prior CD19-directed therapy
Study treatment
Lymphodepleting chemotherapy prior to infusion
Fluda (30 mg/sqm/d IV, 4 days)
Cy (500 mg/sqm/d IV, for 2 days)
Target CTL019 dosing (single infusion)
2.0 – 5.0 x 106/kg for patients ≤ 50 kg
1.0 – 2.5 x 108 for patients > 50 kg
Maude SL, NEJM 2018
ELIANA-CTL019 global trial: R/R BCP-ALL
Maude SL, NEJM 2018
Efficacy % (n/N) 95%CI p-value
Primary
- CR+CRi within 3 months82%
(41/50)69%-91% <.0001
- CR 68%
- Cri 14%
Secondary
- Achieved BOR (CR/CRi) with
MRD-82% 69%-91%
<.0001
ELIANA-CTL019 global trial: R/R BCP-ALL
Maude SL, NEJM 2018
ELIANA-CTL019 global trial: R/R BCP-ALL
Maude SL, NEJM 2018
ZUMA-2 trial: R/R Lymphoma
Eligibility criteria
Inclusion : R/R BCP-Lymphoma, age 18-60 years
Study treatment
Lymphodepleting chemotherapy prior to infusion
Fluda (30 mg/sqm/d IV, 3 days)
Cy (500 mg/sqm/d IV, for 3 days)
Target CTL019 dosing (single infusion)
2.0 x 106/kg
Neelapu SS, NEJM 2017
ZUMA-2 trial: R/R Lymphoma
Neelapu SS, NEJM 2017
ZUMA-2 trial: R/R Lymphoma
Neelapu SS, NEJM 2017
CAR-T cells en oncologie
Antigènes cibles
Conclusions et perspectives
2 AMM
Kymriah® dans les LAL et les lymphomes
Yescarta® dans les lymphomes
5 centres qualifiés en France
Pharmacie qualifiée pour MTI
Structure pratiquant l’allogreffe de CSH
Réanimation sur site
…
Nombreux essais cliniques de phase 3 en cours
Merci de
votre
attention