focus sur les car-t cells - proinfoscancer...eliana-ctl019 global trial: r/r bcp-all eligibility...
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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
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CAR-T cells 1ère génération
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CAR CAR + IL2
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CAR-T cells 2ème génération
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Hombach, Journal of Immunology 2001
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Hombach, Journal of Immunology 2001
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Hombach, Journal of Immunology 2001
ACE -
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Hombach, Journal of Immunology 2001
ACE -
ACE+ / B7- ACE+ / B7+
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Savolado, JCI 2011
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CAR-T cells 3ème génération
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Sadelain, Nat 2017
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Sadelain, Nat 2017
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Zhao Cancer Cell 2015
NALM6
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Persistance
Zhao Cancer Cell 2015
NALM6
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Persistance
Zhao Cancer Cell 2015
NALM6
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Zhao Cancer Cell 2015
NALM6
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Zhao Cancer Cell 2015
NALM6
Persistance
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Zhao Cancer Cell 2015
NALM6
Persistance
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Sadelain, Nat 2017
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Sadelain, Nat 2017
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CAR-T cells nième génération
CAR-T cells « actionnable »
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Wu Science 2015
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Juillerat Sci Reports 2015
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CAR-T cells nième génération
CAR-T cells « universels »
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Eyquem Nature 2017
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CAR-T cells « en pratique »
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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
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Davila, Oncoimmunology. 2012 Dec 1;1(9):1577-1583
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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
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ELIANA-CTL019 global trial: R/R BCP-ALL
Maude SL, NEJM 2018
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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
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ELIANA-CTL019 global trial: R/R BCP-ALL
Maude SL, NEJM 2018
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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
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ZUMA-2 trial: R/R Lymphoma
Neelapu SS, NEJM 2017
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ZUMA-2 trial: R/R Lymphoma
Neelapu SS, NEJM 2017
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CAR-T cells en oncologie
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Antigènes cibles
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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
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Merci de
votre
attention