CLL Flashcards
Epidemiology
Median age at diagnosis: 70
More common in white males
Pathophysiology
Monoclonal B lymphocyte transformation
Clonal expansion
Lymphocyte accumulation
Risk factors
Occasional family clusters
Male
White
Older age
Presentation
Indolent disease
May be an incidental finding
Constitutional symptoms:
-Lymphadenopathy
-Hepatosplenomegly
-Peripheral lymphocyte doubling time< less than 6 months
-Anemia
-Thrombocytopenia
Cyotogenetics
Del (11q) is associated with extensive lymphadenopathy
Del (17p) is associated with the worst prognosis
-Loss of TP53
Diagnosis
Monoclonal B lymphocytes > or equal to 5 x 10^9 /L in peripheral blood
CD19, CD20
Treatment
We do NOT treat a number
Treatment reserved for:
-Stage III or IV disease
-Clinical symptoms
First Line Treatment
BTK inhibitor +/- anti-CD20 mAb
Venetoclax +/- Obinutuzumab
Chemo-immunotherapy
BTK inhibitor +/- Obinutuzumab
BTK inhibitors
Zanubrutinib
Acalabrutinib
Venetoclax
Inhibits BCL-2 resulting in release of BIM and PUMA
BCL-2 is a pro-survival protein
BIM and PUMA are pro-apoptotic proteins
Venetoclax and Drug interactions!!!
CYP3A4 inhibitors/inducers
P-gp inhibitors and inducers: amiodarone, carvedilol, macrolides, azoles, verapamil, phenytoin, rifampin, carbamazepine, st. johns wort
Relapse or refractory disease
Goal of treatment is to palliate symptoms
Managemt of relapse depends on:
Age and performance status
Previous therapy
Response and duration to therapy
Time from last therapy
Venetoclax tocitites
Tumor lysis syndrome
Ibrutinib toxicities
High risk of Afib
Lymphocytosis or Tumor flare
Transient increase in absolute lymphocyte count
Associated with BTK inhibitors
Resolves by week 12
Does not signify disease progression
