CLL Flashcards

1
Q

One complication of Fludarabine that results in anemia

A

Severe AIHA/ITP. Must discontinue if it occurs and cannot use it again, as the AIHA will return on rechallenge [also avoid pentostatin, cladribine (all purine nucleoside analogs)]

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2
Q

Name 2 indications for consideration of stem cell transplant in CLL

A

Tp53
r/r CLL in young
Richter’s
Ibrutinib failure

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3
Q

4 treatment options for a CLL patient with a high comorbidity index.

A
Ibrutinib or Acalabrutinib + Obinutuzumab 
Venetoclax +Obinutuzumab
Chlorambucil + Obinutuzumab
BR
Also supportive management
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4
Q

Molecular target of Idelalisib

A

PI3K inhibition

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5
Q

Molecular target in Brentuximab

A

CD30 antibody drug conjugate with antimicrotubule agent

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6
Q

Molecular target in Romidepsim

A

Histone deacetylase inhibitor (HDACi)

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7
Q

What is the difference in mechanism of action between Rituximab and Obinutuzumab?

A
  1. Rituximab- Type 1 monoclonal Ab
    - More complement AND cytotoxic mediated cell death
  2. Obinutuzumab- Type 2 monoclonal Ab
    - More Ab-mediated AND apoptosis
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8
Q

List three severe toxicities with Idelalisib therapy?

A

BB warning:

  1. Colitis/diarrhea
  2. Pneumonitis
  3. Transaminitis
  4. Infection (CMV/PJP)
  5. Intestinal perforation.
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9
Q

Major SE of Acalabrutinib

A

Cytopenias
Headache
Upper respiratory tract infection
Diarrhea

Serious, potentially life-threatening, toxicities include opportunistic infections, bleeding, arrhythmias, and second primary malignancies.

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10
Q

What things should you monitor when starting someone on Alemtuzumab?

A
  1. Increased risk of infection (CMV reactivation!, bacterial, fungal)
  2. Lymphopenia
  3. infusion reactions

o CMV, Viral load weekly
O Also monitor clinically for infusion reactions.
o CBC q weekly
o CD4+ lymphocyte count until >/= 200

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11
Q

MOA of Alemtuzumab

A

Recombinant human IgG-derived monoclonal Ab that binds to antigen CD52 which is found on the surface of B and T lymphocytes, most monocytes, macrophages and NK cells, and certain granulocytes, but not hematopoietic stem cells.
-Causes lysis of CD52-positive cells occurs via complement activation, antibody-dependent cytotoxicity, and apoptosis.

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12
Q

Name 5 side effects of Rituximab?

A
  1. Infusion reaction
  2. Neutropenia
  3. HBV reactivation
  4. PML
  5. TLS- Do not give if WBC >25!
  6. Infections

Other: renal toxicity if used with cisplastin.

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13
Q

What are 2 potential indications for allo-sct in CLL patients?

A
  1. Ritcher’s transformation (DLBCL, HL)
  2. Tp53
  3. Relapsed, refractory disease

Use induced intensity conditioning.

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14
Q

What are the 3 most common gr 3/4 toxicities of ibrutinib? How do you treat gr 2 rash?

A
  1. Hypertension 29% (Grade 3 is >160/100 or needing >1 drug),
  2. Infection 16%
  3. Neutropenia 13-29%
  4. Anemia 11%
  5. Afib 8%

Gr 2 rash

  • Topical corticosteroids +/- oral antihistamine
  • Continue ibrutinib and monitor
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15
Q

Define MBL. Low count vs. High count. Annual risk of conversion to CLL. What two other thing would you counsel the pt on?

A

Clonal B-cell population with no LAD, cytopenias.
Low count: clonal B cell population <0.5 x 10’9 g/l
High count: 2-5x 10’9 g/l
Risk of progression to CLL:1-1.5%/ yr (new evidence that low count is also at similar risk)
Counsel: 1) increased secondary malignancy
2) increased infxn risk.

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16
Q

What is the CLL-IPI score?

A

“Ba65si-53”
BASIC (b2, age, stage, ighv, cyto)

B2µg >3.5 (2)
Age >65 (1)
Stage 1-4 (1)
IGHV unmutated (2)
17p/TP53 aberration (4)
o	Cutoffs: 0-1= low, 2-3=intermediate risk, 4-6=high, 7-10-very high
17
Q

What are the 6 indications for treatment of CLL?

A
  1. ITP or AIHA not responsive to therapy
  2. Hg <110, plt <100
  3. Lymphocyte doubling time <6months, or >50% in 2 months (relative)
  4. Constitutional symptoms
  5. Bulky LAD, >10cm
  6. Enlarging spleen >6cm
18
Q

4 patient/disease characteristics that would lead you to offer FCR in the upfront setting for a pt with CLL?

A
  1. Age<65
  2. FIT
  3. No Tp53 or 17p
  4. IGHV mutated!
19
Q

2 options for relapsed/refractory CLL after failing ibrutinib.

A
  1. PI3k inhibitor-idelalisib + rituximab
  2. BCL2 inhibitor-venetoclax+Rituximab

Duvelisib approved for relapsed CLL

20
Q

Very low risk cytogenetic abnormality in CLL?

A

del13q

21
Q

Low risk cytogenetic abnormality in CLL?

A

normal karyotype, trisomy 12

22
Q

Intermediate risk molecular/cytogenetic abnormality in CLL?

A

SF3B1, NOTCH 1, 11q23 (KMT2A)

23
Q

High risk molecular/cytogenetic abnormality in CLL?

A

TP53, BIRC3 abnormalities