CLL

Question 1

What cytogenetic markers carry a poor prognosis?

Answer 1

Del 17p (TP53), Del 11q

Question 1

What cytogenetic features carry a intermediate prognosis?

Answer 1

Trisomy 12, normal cytogenetics

Question 2

Which cytogenetic feature is associated with a good prognosis?

Answer 2

Del 13 q alone

Question 3

What DNA mutation is associated with a poor prognosis?

Answer 3

Mutated Tp53

Question 4

What IGHV chain status is assoc with a poor and good prognosis?

Answer 4

Mutated IGHV less than or equal to 2% has a poor prognosis while greater than 2% has a good prognosis.

Question 5

What is the flow phenotype for CLL?

Answer 5

CD5+, CD23+, CD43+/-, CD19+, CD20 dim, sIg dim+, CD10 neg

Question 6

What is the difference between CLL vs SLL? Monoclonal B-Cell Lymphocytosis?

Answer 6

CLL>5,000 cells
SLL<5,0000 cells
Monoclonal<5,000 cells with no active disease and no symptoms

Question 6

What is the criteria for the different stages of CLL?

Answer 6

Stage 0-lymphocytosis
Stage I-Lymphadenopathy
Stage II-Splenomegaly
Stage III-Anemia
Stage IV-Thrombocytopenia

Question 7

What are indications to treat CLL?

Answer 7

Cytopenias (Hgb<10, platelets<100), symptomatic lymph nodes (particularly bulky nodes,>10cm), symptomatic extranodal disease, symptomatic splenomegaly (>6cm or symptoms w/o 6cm), refractory autoimmune thrombocytopenia and anemia, Constitutional Symptoms

Question 8

What are the first line recommendations for CLL in patients without del 17p/TP53 mutation?

Answer 8

Acalabrutinib +/-Obintuzumab, Venetoclax+Obintuzumab,
Zanabrutinib

Question 9

When using FCR for those without del 17p/TP53 wild type, who is this indicated for? What is the survival benefit in this patient population?

Answer 9

You use in patients younger than 65 years of age with no comorbidities in high IGHV mutated patients, in this age group there is a PFS benefit. Very helpful for heavy disease burden.

Question 10

What are the options for first line treatment for patients who have TP53/del 17p?

Answer 10

Basically the same options as for lower risk patients: Acalabrutinib +/-Obintuzumab, Venetoclax+Obintuzumab,
Zanabrutinib

Question 11

What treatment combo is not indicated in patients who have del 17p or TP53 mutation due to low response rates?

Answer 11

Chemo-immunotherapy combo (e.g. Bendamustine/Rituximab).

Question 12

What are second line options for patients with relapsed/refractory disease?

Answer 12

In general you can consider a BTK inhibitor alone (Acalabrutinib or Zanabrutinib) or you can do Venetoclax+Rituximab (cat 1 recommendation). Ibrutinib (cat 1 recc)

Question 13

What is the value of Ibrutinib in the second line setting of CLL?

Answer 13

It is associated with a PFS and OS benefit and this is regardless of whether or not they have high risk or low risk disease.

Question 14

What are the PI3K inhibitors approved for refractory CLL and what setting are they indicated for?

Answer 14

You can use Duvelisib or Idelalisib +/- Rituximab. You use in the third line setting. Remember that there is a bit of toxicity to these agents.

Question 15

What are some toxicities assoc with PI3K inhibitors?

Answer 15

Diarrhea, pneumonitis, transaminitis, colitis, infection

Question 16

For those that develop resistance to BTK inhibitors whats the reason and what treatment can be offered here?

Answer 16

They have mutation changes in the BTK receptor so using a non-covalant BTK inhibitor can help overcome this-Pirtobrutinib

Question 17

For those patients who develop immune complications from CLL how do you treat these patients? For those who relapse or have refractory disease? They love to ask this!

Answer 17

So you first treat with steroids, IVIG, Rituximab, Cyclosporine, TPO agonists. For those with refractory or relapse you then use BTK directed therapy.

Question 18

What are the immune complications that can occur with CLL? Very important!!!

Answer 18

Autoimmune hemolytic anemia and thrombocytopenia. Patients can also develop pure red cell aplasia.

Question 19

What can you retreat patients with in the refractory setting if they don’t have del 17p or TP53 mutation?

Answer 19

Veneoclax+Obintuzumab if they had a durable response to treatment.