INCIDENCE OF IMMUNE RELATED ADVERSE EVENTS IN PATIENTS ≥ 70 YEARS OLD
TREATED WITH ANTI-PD-(L)1 THERAPY
C. Baldini* 1, P. Martin Romano1, AL. Voisin2, FX. Danlos1, S.Champiat1, S. Laghouati2, M. Kfouri1, H. Vincent3, S. Postel-Vinay1, A. Varga1, V. Ribrag1,
B.Besse3, E. Angevin1, A. Hollebecque1, O. Lambotte4, JM Michot1, JC. Soria5, C. Massard1, A. Marabelle1
1Gustave Roussy, Dug Development Department (DITEP), Villejuif, France;2Unité de Pharmacovigilance, Gustave Roussy, Université Paris-Saclay, Drug Development Department (DITEP), Villejuif, F-
94805; 3Medical Oncology, Gustave Roussy, Université Paris-Saclay, Drug Development Department (DITEP), Villejuif, F-94805; 4Medecine Interne, Hôpital Kremlin Bicêtre, Kremlin Bicêtre, France, 5Medimmune, Gaithersburg, United States
Disclosure
I have the following the conflict(s) of interest to declare:
BMS, Roche, Sanofi, MSD, Pfizer, Novartis, Sandoz, Celgene, Astellas, Hospira, AbbVie, Merck, Janssen
• Broad spectrum of activity• Fewer toxicities• Interesting option in older patients
Background
Borghaei et al. NEJM 2015
Background
2012
2050
1/3 patients ≥ 75 years old 1/2 patients
≥ 75 years old
Silver tsunami is coming
Kendal WS. Cancer 2009French National Cancer Institute 2014
• Impact of the increasing number of auto-antibodies with aging ?
Background
• Impact of immunosenescence on efficacy ?
Inflammation
Immune agingEfficient immune response, diversity
Nagele EP et al. Plos One 2013Candore et al. Arch Gerontol Geriatr 2002Ferrara et al ESMO 2018
• Evaluate the incidence of immune related adverse events inpatients aged 70 years old or above compared to their youngercounterparts
• Compare median time to toxicity between the two groups
• Compare survival between the 2 groups
Objectives
615 patients treated by anti PD-(L)1
REISAMIC database
Methods
≥ 70 years old (OP) 191 patients
< 70 years old (YP) 424 patients
165 irAEs ≥ grade 2
June 2014 October 2017
“Registre des
Effets
Indésirables
Sévères des
Anticorps
Monoclonaux
Immunomodulateurs en
Cancérologie”
REISAMIC database
Prospective enrollment of patients
• Incidence of irAEs of
grade ≥ 2
• Comparison between
patients aged ≥ 70 and
< 70 years old using
Chi-squared test
• PFS and OS calculated
using Kaplan Meier
Method
Results – Baseline characteristics
< 70 years oldn = 424
70 years oldn =191
GenderMaleFemale
230 (56%)182 (44%)
117 (61%)74 (39%)
Median age 59 (16 – 69) 77 (70 – 93)
Tumor typeMelanomaNSCLC
SCCAdenocarcinomaOther
RCCUrothelialHNSCCMerkel
206 (50%)177 (43%)45 (11%)
119 (29%)13 (3%)10 (2%)9 (2%)
2 (<1%)3 (<1%)
127 (63%)52 (27%)22 (12%)29 (15%)1 (<1%)
07 (4%)
1 (<1%)2 (1%)
Median number of previous lines
1 (0-10) 1 (0-10)
Median ECOG Performans status
1 (0-4) 1 (0-4)
dNLR > 3 242 (59%) 128 (67%)
Patients
< 70 years oldn = 424
70 years oldn =191
Median time under treatment (months)
20.8 (15.7 – 28.4) 23.3 (13.9 – 28.3)
Previous ICIAnti CTLA4Anti PD(L)-1
58 (14%)33 (8%)
19 (10%)9 (5%)
Corticosteroids use> 20mg
107 (26%)79 (74%)
30 (16%)25 (83%)
Anti PD-1NivolumabPembrolizumab
Anti PD-L1AvelumabAtezolizumab
217 (53%)185 (45%)
2 (<1%)8 (2%)
68 (36%)114 (60%)
2 (1%)7 (4%)
Results – Baseline characteristics
Treatments
Incidence of irAEs
0
50
100
150
200
250
300
350
400
450
< 70 ≥ 70
irAEs ≥ grade 2according to age
irAEs ≥ grade 2 no irAEs or grade 1
Nu
mb
er
of
pat
ien
tsirAEs 95% CI p
<70 (YP) 0.25 0.21- 0.29 0.035
≥ 70 (OP) 0.33 0.26 - 0.40
25% 33%
Type of irAEs
0 10 20 30 40 50 60
Skin
Lung
Liver
GI
Endocrine
Pancreas
Other
Type of toxicities according to age
< 70
≥ 70
Proportion of patients (%)
Corticosteroids use:29% in OP32% in YP
Median time under corticosteroids:124 days for OP131 days for YP
Time to irAEs
0
5
10
15
20
25
30
35
0 1 2 3 4 5 6 > 6
Kinetics of toxicities according to age
≥ 70
< 70
Pro
po
rtio
n o
f p
atie
nts
(%
)
Time in months
Similar median time to toxicity : 10 weeks in YP and 6 weeks in OP p=0.13
Reasons for stopping anti PD-(L)1
Toxicity
Progressive disease
Complete response/remission
Other
Reasons for stopping anti PD-(L)1
Toxicity
Progressive disease
Complete response/remission
other
Reasons for stopping therapy
YPs OPs
14%7%
Survival – PFS according to irAEs and age
Number at risk
No IrAEsIrAEs
433165
8593
4050
109
10
0.00
0.25
0.50
0.75
1.00
0 10 20 30 40
IrAEsNo IrAEs
0 10 20 30 40
0.00
0.25
0.50
0.75
1.00
Number at riskYPOP
408189
11464
6426
136
01
OP
YP
irAEs Median PFS: NR (95%CI 24.5 – NR) No irAEs Median PFS : 5 m (95%CI 4 – 5.55)
p < 0.0001
OP Median PFS : 8 m (95%CI 5.9 – 15.7)YP Median PFS: 6 m (95%CI 5.5 – 6.9)
p=0.12
Number at risk
No IrAEsIrAEs
12663
2836
1115
33
0.00
0.25
0.50
0.75
1.00
0 10 20 30 40
IrAEsNo IrAEs
10
irAEs Median PFS: 23 m (95%CI 15.7 – NR) No irAEs Median PFS : 5 m (95%CI 3.9 – 6.4)
p < 0.0001
IrAEs Age
OS according to irAEs and age
No IrAEsIrAEs
438165
110104
4155
912
10
IrAEsNo IrAEs
0.00
0.25
0.50
0.75
1.00
0 10 20 30 40Number at risk
0.00
0.25
0.50
0.75
1.00
0 10 20 30 40
OP
YP
Number at riskYPOP
14470
6531
156
01
424191
irAEs Median OS : 36 m (95%CI 23.9 – NR)No irAEs Median OS: 6 m (95%CI 5.3 – 7.1);
p < 0.0001
OP Median OS : 12 m (95%CI 8.5 – 21.3)YP Median OS: 9 m (95%CI 7.1 – 10.2);
p=0.07
IrAEs Age
• Strength: Prospective real life data analysis
• Anti-PD(L)1 immunotherapies are an acceptable treatment option for OPs, by being aware that immune related adverse events are more frequent in this population.
• Further dedicated studies are warranted to explore prospectively immune-related safety in OPs and correlation with geriatricparameters.
• Main limitation: no geriatric data available in the database
• Impact: Older patients should be monitored closely as they may be at risk of increased significant immune-related toxicity compared to their younger counterparts.
Conclusions
Ackowledgements
Patients and their families
✓ Dr Massard✓ Dr Marabelle✓ Pr Soria✓ Dr Martin-Romano✓ Dr Varga✓ Dr Champiat✓ Dr Michot✓ Dr Hollebecque✓ Dr Angevin✓ Dr Postel Vinay✓ Pr Lambotte✓ Pr Besse✓ Dr Vincent✓ Dr Voisin✓ Dr Laghouati