malignant haemotology

Question 1

Midostaurin

Answer 1

FLT3 receptor inhibitor. In AML FLT3 receptor is mutated which causes abnormal proliferation of leukaemic cells. Inhibition prevents this but FLT3 also influences hematopoietic cell growth and hence inhibition can lead to anaemia, etc.
Taken orally once a day.
Second gen FLT3 inhibitor: gilterinib

Question 2

Azacitidine

Answer 2

DNA methyltransferase inhibitor. DNA methyltransferase silences tumour suppressor genes when it adds a methyl group to it. Hence inhibition reverses this, potentially restoring the function of the genes to help control cancer growth.
Taken SC for 7 days in a 28-day cycle.
Inhibition of methyltransferases can affect both cancerous as well as normal hematopoietic cells so we may see worsening of blood cell counts (cytopenias).

Question 3

BiTE therapy

Answer 3

Blinatumomab: targeted therapy for B-cell ALL. It is a type of bispecific T-cell engager (BiTE) therapy.
Binds to CD3 on T cells and CD19 on B cells which brings them in proximity to each other, facilitating T cell’s ability to recognise and kill cancerous B cells.
SE: CRS- binding to T cells releases cytokines which can cause fever, nausea, encephalopathy.

Question 4

CAR-T therapy

Answer 4

CART- chimeic antigen receptor t cells –> T cells are engineered to respond to recognise specific antigens on the surface of cancer cells. The T cells proliferate and seek out cancer cells that expresses the target antigen (e.g. CD19). This is done by collecting the T cells from a patient, genetically modifying it in the lab and reinfusing it back into the bloodstream.
- used in relapsed B-ALL and diffuse large b-cell lymphoma.
SE: CRS and neurotoxicity – disorientation and confusion, can use dexamethasone to reduce inflammation and manage symptoms of neurotoxicity.

Question 5

treatment for CML?

Answer 5

in CML if Philadelphia chromosome positive, use TKIs: imatinib, dasatinib, nilotinib.
translocation of parts of the chromosome 9 and 22 gene creates BRC-AB1 gene fusion which causes uncontrolled proliferation of myeloid cells. TKIs inhibit this gene fusion.
adherence is critical; <90% = poor outcome.

Question 6

Ibrutinib

Answer 6

Ibrutinib inhibits Bruton’s Tyrosine Kinase (BTK), a crucial enzyme that chronic lymphocytic leukaemia (CLL) cells rely on for their survival and proliferation. By blocking BTK, ibrutinib disrupts the signalling pathways that support the growth and maintenance of these cancer cells.
SE:
- bleeding
- cardiac issues
- infections

Question 7

Venetoclax

Answer 7

Venetoclax works by inhibiting Bcl-2, a protein that helps cancer cells avoid apoptosis (programmed cell death). By blocking Bcl-2, venetoclax promotes the self-destruction of these cancer cells.

SE: TLS- large number of cancer cells die rapidly which releases their intracellular contents into the bloodstream which can affect electrolyte levels, which can lead to kidney damage.
- cytopenia: can decrease RBC, WBC, and platelets.
-imunosuppresion