CLL

Question 1

Typical clinical course with CLL

Answer 1

While most patients will have an initial CR or PR, ALL will relapse eventually.

Question 2

Preferred first line options for CLL

Answer 2

1) venetoclax + obinutuzumab
2) acalabrutinib + obinutuzumab

Question 3

CLL drug classes

Answer 3

• Bruton’s tyrosine kinase [BTK] inhibitors
• PI3-kinase inhibitors
• BCL2 inhibitors
• novel antibodies and other investigational therapies (eg, chimeric antigen receptor T cells)

Question 4

clinical significance of IgVH mutational status

Answer 4

= mutated immunoglobulin heavy chain variable
- UNmutated = shorter survival overall and a higher risk of relapse following conventional treatment, including chemoimmunotherapy and hematopoietic cell transplantation

Question 5

13q deletion clinical significance

Answer 5

very good prognosis because the median time for survival (that is, 50 percent survival) is almost

Question 6

17q deletion clinical significance

Answer 6

1) poor prognosis (median survival historically only 3 years from the time of diagnosis)
2) predicts lack of benefit from standard chemoimmunotherapy
3) Favorable response to ibrutinib

Question 7

11q deletion clinical significance

Answer 7

poor prognosis

Question 8

most common adult leukemia

Answer 8

CLL

Question 9

median age at diagnosis

Answer 9

72

Question 10

CLL RF’s

Answer 10

Male, older age, caucasian

Question 11

Variables involved in CLL staging

Answer 11

• lymphocytosis
• presence of hepatomegaly and splenomegaly
• presence of cytopenias
• **no imaging

Question 12

What typically leads to CLL diagnosis?

Answer 12

• incidental lymphocytosis

- asymptomatic lymphadenopathy

Question 13

presentation

Answer 13

• fatigue and malaise, early satiety, abdominal discomfort (splenomegaly), B symptoms (fevers, night sweats, weight loss), recurrent infections

Question 14

Diagnostic criteria + what is required for diagnosis

Answer 14

1) Peripheral blood B-lymphocyte count >5K
2) Flow cytometry confirmation of circulating B lymphocyte clonality (CD5+ + CD23+)
3) Percentage of prolymphocytes <55% of lymphocytes
* BMB not needed. Just flow cytometry.

Question 15

typical cell surface markers

Answer 15

CD5, CD19, CD23

Question 16

average time to initiation of therapy

Answer 16

4-5 years

Question 17

CLL workup

Answer 17

FISH
Flow cytometry
Immunohistochemistry
NO BMB needed

Question 18

Poor prognosticator on FISH testing

Answer 18

Deletion 17p (OS 2-3 years)
Deletion 11q (OS 6-7 years)

Question 19

Favorable prognosticator on FISH testing

Answer 19

Deletion 13q

Question 20

Factors that influence treatment strategy

Answer 20

Age
Functional status and comorbidities
Cytogenetics

Question 21

management of AIHA in CLL

Answer 21

IF indication for CLL exists independent of anemia –> treat CLL
IF no indication for CLL treatment: steroids + folic acid, followed by SLOW taper

Question 22

common side effects of ibrutinib

Answer 22

Diarrhea + peripheral lymphocytosis (may look like CLL progression but is not) + rash + Afib + antiplatelet effect (increased bleeding risk)

Question 23

Contraindication to ibrutinib

Answer 23

patient on anticoagulation

Question 24

purine analogs

Answer 24

pentostatin and cladribine

Question 25

prophylaxis when using alemtuzumab

Answer 25

- acyclovir for HSV ppx | - PCP prophylaxis with bactrim

Question 26

prophylaxis when using purine analogs

Answer 26

- acyclovir for HSV ppx | - PCP prophylaxis with bactrim

Question 27

what is richter's transformation + clinical importance

Answer 27

Extraordinarily rare transformation of CLL or hairy cell leukemia into a fast-growing DLBCL. Very bad prognosis.

Question 28

treatment of richter's transformation

Answer 28

Same treatment as for DLBCL

Question 29

treatment regimen depends on...

Answer 29

presence of 17p deletion (but preferred first line regimens are the same with and without)

Question 30

Labs

Answer 30

absolute lymphocytosis (threshold = 5K but can be up to 100K) + hemolytic anemia + hypogammaglobulinemia (25%) + mild cytopenias (neutropenia, anemia, thrombocytopenia) + elevated LDH

Question 31

Major branch point in management

Answer 31

Presence of 17p mutation

Question 32

Indications for starting treatment

Answer 32

1) Evidence of progressive marrow failure (worsening anemia and/or thrombocytopenia) 2) Massive (ie, ≥6 cm below the left costal margin) or progressive or symptomatic splenomegaly 3) Massive (ie, ≥10 cm in longest diameter) or progressive or symptomatic lymphadenopathy 4) Progressive lymphocytosis with an increase of >50 percent over a two-month period or lymphocyte doubling time (LDT) of <6 months. constitutional symptoms (Significant fatigue (ie, Eastern Cooperative Oncology Group performance status [ECOG PS] ≤2, inability to perform usual activities), Night sweats for ≥1 month without evidence of infection, Unintentional weight loss ≥10 percent within the previous six months, Fevers for ≥2 weeks without other evidence of infection

Question 33

Clinical staging system for CLL

Answer 33

Rai

Question 34

CLL labs

Answer 34

absolute lymphocytosis (threshold = 5K but can be up to 100K) + hemolytic anemia + hypogammaglobulinemia (25%) + mild cytopenias (neutropenia, anemia, thrombocytopenia) + elevated LDH

Question 35

CLL diagnosis

Answer 35

Peripheral blood B-lymphocyte count >5K + Characteristic immunophenotype = Flow cytometry with CD5+ + CD23+ Also -- Percentage of prolymphocytes <55% of lymphocytes *BMB not needed.

Question 36

Important cytogenetic markers in CLL

Answer 36

11,13,17

Question 37

CLL vs. B cell SLL

Answer 37

The term CLL is used when the disease manifests primarily in the blood, whereas the term SLL is used when involvement is primarily nodal.

Question 38

Disease warranting treatment in CLL is referred to as

Answer 38

"active disease"

Question 39

CLL clinical course

Answer 39

extremely heterogeneous disease with certain subsets of patients having survival rates without treatment that are similar to the normal population

Question 40

Criteria for defining massive splenomegaly

Answer 40

Greater than 6 cm below the left costal margin

Question 41

Adverse prognostic features

Answer 41

- low ZAP-70 - CD38 - P53 mutant - unmutated IGHV

Question 42

Major branch point in selection of initial systemic therapy

Answer 42

Presence of 17p deletion, TP53 mutational status

Question 43

Term for premalignant phase

Answer 43

MBL (monoclonal b lymphocytosis)

Question 44

Cutoff levels for cytopenias that are typically used to initiate treatment and caveat

Answer 44

- Hgb <10 - plt count <100k * assuming declining, some people have stable platelet counts below 100k and don't need treatment

Question 45

clinical significance of ZAP-70 + interpretation

Answer 45

- Surrogate for IGHV mutation status but it will change overtime, unlike IGHV - Low is good (correlates to mutated IGHv)

Question 46

predictive vs. prognostic

Answer 46

``` prognostic = independent of treatment predictive = response with treatment ```

Question 47

prognosis of patients who transform to DLBCL (Richter's)

Answer 47

Absolutely dismal (worse than FL transformation)

Question 48

Clinical significance of TP53 mutation

Answer 48

TP53 mutations are both predictive of worse clinical outcomes with chemoimmunotherapy as compared to targeted therapies (eg, BTK or BCL2 inhibitors)

Question 49

Preferred BTK inhibitor and why

Answer 49

- acalabrutinib - less cardiotoxicity

Question 50

highest risk cytogenetic finding

Answer 50

17p deletion (tp53)

Question 51

11q significance in CLL

Answer 51

intermediate, can be overcome by newer therapies