Immune-response markers and actual ... - Caris Life Sciences
Transcript of Immune-response markers and actual ... - Caris Life Sciences
KEY FINDINGS: • IO therapy was associated with a median OS benefit of > 2 years.• We did not identify any prognostic markers of IO-therapy response.• MSI-H and TMB-H are rare in USC, but PD-L1 is present in nearly
20% of cases. • Notably these markers did trended toward a survival benefit, which
could have important clinical implications. Further study is warranted.
Immune-response markers and actual response to immune-oncology therapy in uterine serous carcinoma.
NL Jones1, S Wu2, J Xiu2, A Craig3, G Smaldone3, E Hernandez3, RP Rocconi1, J Brown4, T Herzog5, R Holloway6, WM Korn2, M Powell7, AM Wilhite1
1University of South Alabama, Mobile, AL 2Caris Life Sciences, Phoenix, AZ 3Temple University, Philadelphia, PA 4Atrium Health, Charlotte, NC 6University of Cincinnati, Cincinnati, OH 6 AdventHealth Cancer Institute, Orlando, FL 7Washington University, St. Louis, MO
Results: Figure 4: Immune microenvironment characterized by immune-cell fraction.
1000 3000 4000 50000Time, days
1.0
0.8
0.6
0.4
0.2
0.0
Even
t fre
e pr
opor
tion
Figure 2: Treatment with IO therapy in USC had a significantly improved median overall survival benefit of more than 28 months. A
• Uterine serous carcinoma (USC) is an aggressive type of endometrial cancer with poor prognosis and limited treatment options.
• Immune-oncology (IO) agents have shown promise USC, though data is limited regarding which patients benefit most from IO therapy.
• In other malignancies, PD-L1, MSI-H status and high TMB have been predictive of IO response.
Median OS 59.6 vs 31.2 months; HR(95% CI):
0.38(0.24-0.61) p <0.001
c
characterize the immune profiles of USC and investigate treatment response to IO therapy
1.0
0.8
0.6
0.4
0.2
0.0
Even
t fre
e pr
opor
tion
1000 2000 3000 40000Time, days
Figure 5: Patients with IO therapy response markers trended toward a better median survival, but this was not significant; A. MSI-H (OS not yet reached vs 31.6 months; HR(95% CI): 0.69(0.38-1.25) , B. TMB-H (months: 36.4 vs 31.6; HR(95% CI): 0.84(0.50-1.39). C. PD-L1 (months: 34.4 vs 31.2; HR(95% CI): 0.90 (0.74-1.1),
A
B
Objective:
Background:
2000 6000
USC with IO therapy (n=92)USC without IO therapy (n=2306)
0%5%
10%15%20%25%
% A
ltere
d
TMB-H PD-L1MSI-H
Figure 3: Markers of response to IO therapy. Serous tumors were low in microsatellite instability and tumor mutation burden. Nearly 20% expressed PD-L1.
4.2%
19.1%
2.3%
Immune CellB cell 4.71%
Macrophage M1 1.35%Macrophage M2 5.35%
Monocyte 0.00%Neutrophil 2.10%
NK cell 2.94%T cell CD4+ (non-regulatory) 0.00%
T cell CD8+ 0.12%T cell regulatory (Tregs) 1.59%
Myeloid dendritic cell 3.45%uncharacterized cell 74.78%
B ce
ll
Mac
roph
age
M1
Mac
roph
age
M2
Mon
ocyt
e
Neu
troph
il
NK
cell
T ce
ll C
D 4
+
T ce
ll C
D8+
T re
g
mye
loid
den
driti
c
50%
40%
30%
20%
10%
0%
1.0
0.8
0.6
0.4
0.2
0.0
Even
t fre
e pr
opor
tion
2000 4000 60000Time, days
1000 2000 3000 40000Time, days
1.0
0.8
0.6
0.4
0.2
0.0
Even
t fre
e pr
opor
tion
MSI-H (n=43)
MSS (n=1463)
TMB high (n=43)
TMB low (n=807)
PD-L1 pos (n=308)
PD-L1 neg (n=1543)
C
- Statistical significance determined by chi-square and Wilcoxon rank sum test.
- p values adjusted for multiple comparisons (q) to be <0.05
- Survival calculated using CodeAI data
CODEai insurance claims data
2806 USC tumors
NextGen DNA sequencing
RNA sequencing
Immunohisto-chemistry
Comprehensive tumor profiling (Caris
Life Sciences)
Methods:
Analysis
Figure 1: Flowchart describing methods