CLL Flashcards
Immunophenotype
CD5 CD19 CD20 CD22 CD23 CD200
Kappa/Lambda restriction
FMC7-
CD10 -
prognostic factors
bad:
unmutated IGHV
del13q14
trisomy12,
del6q23,
del17p13
good:
del11q23
Blood smear
round lymph.
smudge cells
MBL
Clonality but < 5K lymp
no lymphadeno./splenomegaly/cytopenia
1-2% to become CLL
Flow cytometry prognostic factors
CD49d- most powerful flow-cytometry predictor of OS (not available in labs)
IGHV
ZAP-70
CD38
NGS
TP53
NOTCH
SF3B1
CLL-IPI
concordance of 70%
age >65
rai >= 1
beta-2 microglobulin ≥3.5
del17p13 or TP53
unmutated IGHV
0–1 Low
2–3 Intermediate
4–6 High
7–10 Very high
Diagnosis
FACS
no need usually for BM or lymph biospy
tests for CLL-IPI
iwCLL Criteria for initiation of CLL therapy
- Progressive marrow failure
- Symptomatic splenomegaly.
- Symptomatic lymphadenopathy.
- Autoimmune complications poorly responsive to corticosteroids.
- Symptomatic extranodal involvement (eg, skin, kidney, lung, spine).
- B symptoms
Ibrutinib common side effects
bleeding 2-3%
AF 11%
HTN 20-30%
Arthralgias
Ventoclax common side effects
TLS
Acalabrutinib vs ibrutinib
less side effects with acala
cannot use PPi with acala
acal is bid and ibruti is qd
more FU with ibruti and more info with P53 mut
When to add obintuzumab
need for rapid response
glomerulonephritis/extranodal diseas
role of MRD
important to measure
but, does not change Tx decision
IPS-E
The International Prognostic Score for Early-stage CLL
Predicts time to treament:
Unmutated IGHV
Lymphocytes >15,000/microL,
Palpable lymph nodes
Tx protocols
Ibrutinib until progression
I +R/G until progression (AYA)
Acalabrutinib +/- G until progression
ven + G for 12 months
CR def
lymph< 4K
no B symptoms
no BM failure
lymphedeno. < 1.5 cm
no hepato-splenomegaly
PR def
2 of 3
Lymph decrease of > 50%
lymphedenopathy decrease > 50%
decrease of hepato-splenomegaly > 50%
and
PLT > 100K
or
HB 11> g% or > 50% above baseline
Ibrutinib AE
AF
Bleeding
Acalabrutinib AE
Diarrhea
Rash
IGHV mutated %
50%
MBL definition
monoclonal lymphocytosis of less than 5K with no lymphadenpathy, organomegaly ,cytopenias or B symp.
MBL prevelence
X100 of CLL
high/low count MBL
high > 500
low < 500
MBL types
CLL like type- CD20 dim/negative
atypical CLL type- CD20 bright
non-CLL type- CD5 neg
MBL associated disease
Infections X4
Progression to CLL 1-2% per year
non-hematologic cancer X2
MBL monitoring
Twice a year for 2 years
then annually
Mutated/Unmutated
30-50%/50-70%
Time to first treatment
Unmutated
Lymphocytes > 15K
Palpable lympadenopathy
CLL risk in 1st degree relatives
X6-9
FISH
del13q14 - Favorable
trisomy12, del6q23, del11q23- Unfavorable
del17p13- shortest OS
Follow up for patients with no need for treatment based on IPI
High-Very high risk- 3-6 months
Low -Intermediate risk - 6-12 months
Role of MRD
Heavy chain PCR
Very sensitive but not yet a clinical tool. Decisions should not be based on results of MRD
Venetoclax ramp up
Starting a week after 3rd 1/w Gazyva followed by
20 mg
50 mg
100 mg
200 mg
400 mg
each for 1 week
Venteoclax+ Ibrutinib
for high risk patients
age> 65, del17, del11 or TP53 mutation
2 year fixed duration
PFS and OS exceeded 95%
Cumulative Illness Rating Scale (CIRS)
0-4
Evaluates comorbidly in each system separately
Venetoclax vs. Ibrutinib
Ventoclax- fixed duration, less AF and bleeding, caution with renal failure, need for more intense follow up.
Ibrutnib- more infeormaton with P53
Options for R/R naïve to novel Tx
try Clinical trial, else:
=if (OR(TP53 mut, del17p13), BTKi, choices)
choices = {BTKi, Venetoclax, Obinutuzumab)
