Mehrdad Payandeh Department of Hematology and Oncology Kermanshah University of Medical Sciences Kermanshah Iran August 1819 2016 London UK Faculty Edris Sadeghi MSc ID: 930355
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Slide1
Survival and Clinical Aspects for Patients with Chronic Lymphocytic Leukemia in Kermanshah, Iran
Mehrdad
Payandeh
Department of Hematology and Oncology,
Kermanshah University of Medical Sciences, Kermanshah, Iran
August 18-19, 2016 London, UK
Slide2Faculty
Edris
Sadeghi
,
MSc
Medical Researcher
Department
of Hematologic
Malignancies, Medical Oncology
Kermanshah University of Medical Sciences
Kermanshah, Iran
Masoud
Sadeghi
,
MSc
Medical Researcher
Department of Hematologic Malignancies, Medical Oncology
Kermanshah University of Medical Sciences
Kermanshah, Iran
Slide3Background
Chronic lymphocytic leukemia (CLL), most common leukemia in adults in Western countries but is relatively rare in Asia
Slide4Chronic Lymphocytic Leukemia
~ 15,000 new cases per yr
Most common adult leukemia
Chronic, incurable, mature B-cell neoplasm
Most pts present with asymptomatic increase in lymphocyte count
Many asymptomatic pts do not initially require therapy
Therapy required once symptoms,
cytopenias
, or large lymphadenopathy occur
Slide credit:
clinicaloptions.com
Slide51. Puente XS, et al. Nature. 2015;526:519-524.
2.
Stilgenbauer
S, et al. Blood. 2014;123:3247-3254.
3.
Dreger
P, et al. ASH 2012. Abstract 966.
4.
Dreger
P, et al. Blood. 2013;121:3284-3288.
5.
Schnaiter
A, et al. Blood. 2013;122:1266-1270. 6. Schneiter A, et al. ASH 2012. Abstract 710.
Incidence of Genetic Lesion, %Treatment naïve CLL[1](n = 452)CLL8[2]Frontline FC vs FCR(n = 635)CLL3X[3,4]High-Risk AlloSCT(n = 80)CLL2H[5,6]F-Refractory Alemtuzumab(n = 97)TP53mut5.311.530.039.0NOTCH1mut12.610.014.013.4SF3B1mut8.618.426.017.5IGHV UM32.863.096.079.0del(17p)5.38.418.130.1del(11q)16.024.636.119.4
CLL: Incidence of Genetic Lesions
Slide credit:
clinicaloptions.com
Slide6Rossi D, et al. Blood. 2013;121:1403-1412.
Estimate of OS According to Cytogenetics
Slide credit:
clinicaloptions.com
100
80
60
40
20
0
Cumulative Probability of OS (%)
0
5
10
15
P
< .0001
Yrs From Diagnosis
Del(13q14)
Normal/+12
NOTCH1
M/
SF3B1
M/del(11q22-q23)
TP53
DIS/
BIRC3
DIS
Events, n
27
53
41
57
Total, n
155
228
99
101
Median
OS, yrs
NR
13.4
8.5
5.0
95% CI
--
12.1-14.7
5.6-11.5
3.4-6.5
Del(13q14) vs normal/+12
Normal/+12 vs
NOTCH1
M/
SF3B1
M/del(11q22-q23)
NOTCH1
M/
SF3B1
M/del(11q22-q23)
vs TP53
DIS/
BIRC3
DIS
P
= .0406
P
= .0082
P
= .0196
Slide7LYN
SYK
BCR
BTK
PLC
γ2
PKC
PI3K
delta
AKT
mTOR
p70s6k
elf4E
GSK-3
NF-k
β
pathway
Critical Signaling Pathways and New Targeted Agents in B-Cell Malignancies
BCR signaling is required for tumor expansion and proliferation
BCR signaling up-regulated in CLL
New inhibitors are targeting multiple components of BCR signaling including PI3K delta, BTK, and
Syk
Ibrutini
b
┬
┬
Everolimus
┬
Idelalisib
Duvelisib
Pilaralisib
Slide credit:
clinicaloptions.com
Slide8Frontline CLL Therapy in 2016Clinical trial should be considered for all pts with CLL
Population
Initial Therapy
Younger, fit pts
FCR
(
especially mutated
IGHV
)
Older pts with comorbidities
Bendamustine/Rituximab
Chlorambucil/Obinutuzumab
Chlorambucil/Ofatumumab
IbrutinibPts with del(17p) or TP53 mutationIbrutinibAlloSCT?Slide credit: clinicaloptions.com
Slide9Clinical trial should be considered for all pts with CLL
Population
Initial Therapy
Relapsed Therapy
Younger, fit pts with low risk
FCR
(
especially mutated
IGHV
)
Ibrutinib
Idelalisib + R
Ibrutinib
+ BR*Idelalisib + BR*Venetoclax*Older pts with comorbiditiesBendamustine/rituximabChlorambucil/obinutuzumabChlorambucil/ofatumumabIbrutinibIbrutinibIdelalisib + R Pts with del(17p) or TP53 mutationIbrutinibAlloSCT?VenetoclaxIbrutinibIdelalisib + R AlloSCT?CLL Therapy in the Future*Not currently approved by the FDA.Slide credit: clinicaloptions.com
Slide10Materials and Methods In this study, we did a retrospective analysis from 109 CLL patients that referred to Clinic of Hematology- Oncology, Kermanshah, Iran, between January 2006 and March 2014.
Slide11Materials and MethodsFor all of patients were calculated sex, age, survival, AIHA, Evan’s syndrome,
lymphadenopathy
,
organomegaly
, B symptoms, white blood cell, hemoglobin and platelet by patient or pathology reports or laboratory tests.
Slide12Materials and MethodsOverall survival (OS) was calculated as the time from diagnosis to death or last contact.Curve of OS was plotted by Kaplan- Meier plot in Graph Pad prism 5 Software in a five-year period (March 2009 - March 2014) with completing a two-year period and curves of OS for male and female were compared by log-rank test.
Slide13Table 1. The baseline characteristics in the patients at time of diagnosis of chronic lymphocytic leukemia (n=109)
Slide14Patients ResultsOf all patients, 22 patients (20.8%) were treated with IVIG and 46 patients (43.3%) were treated with vaccine of the Flu.
Slide15Patients ResultsOf 109 patients with CLL, 29 patients died and 23 patients were lost to follow-up before completing a two-year period and should therefore be excluded from the analysis.
Slide16Table 2. The Primary Clinical Variables in CLL Patients
Slide17Table 3. Mean age and Percentage of Male for Chronic Lymphocytic Leukemia in Asian Countries
Slide18Table 4. Mean overall survival and survival rate (5- year period) for chronic lymphocytic leukemia in Asian countries
Slide19Treatment ResultsSurvival rate for patients was 64% and mean of overall survival for 5-year period was 38.5 months.
Slide20Treatment ResultsThere is a significant difference between sex and OS rate (P=0.018, 95% CI of ratio 1.14-4.65, Hazard Ratio (HR) 2.31).The survival rate for females is 78% and for males is 53.5%.
Slide21Figure 1. The 5-year overall survival for chronic lymphocytic leukemia for all of patients
Slide22Figure 2. The 5-year overall survival rate for chronic lymphocytic leukemia by sex
Slide23Therefore, it is probably that life conditions (smoking, ,hard work, etc) in males comparing with females have more affect on the appearance and mortality of CLL. In Western Iran (Kermanshah) majority of males work more than females in hard condition and smoking in males is more.
Slide24In previous studies were reported that smoking (Muirhead et al., 2009) and quality of life (Shanafelt
et al., 2009) influence on development of CLL.
Slide25ConclusionFirst of all, CLL is a rare case of malignancy in Asian countries and lymphadenopathy
and
organomegaly
,
immunodeficiencies
and the Flu virus are the main complaints in CLL.
Second, in these countries, CLL is more in males and in ages of above 60 years.
Third, here is not relationship between sex and age in patients.
At last, OS rate in females is higher than males.
Slide26Thank You For Your Attention
Slide27