Cancer (CLL and principles of treatment)

Question 1

What is first line treatment for pts without comorbidities without deletion in 17p or TP53 mutation?

Answer 1

chemoimmunotherapy

FCR (fludarabine + cyclophosphamide + rituxamab)

Question 2

What is first line for older/unfit without del 17p?

Answer 2

BR (bendamustine + rituxamab)

Obinutuzumab + chlorabucil

Question 3

What is the most prognostic cytometry marker?

Answer 3

CD49D

Question 4

What are the side effects of ibrutinib?

Answer 4

Initial response- show elevated lymphocytosis

However this is due to loss of volume of lymphoid tissue

SE- thrombocytopenia, neutropenia, diarrhoea, anaemia, fatigue

Question 5

Describe CAR-T (chimeric antigen receptor T cells) therapy?

Answer 5

T cell collection: Pts own T cells harvested from peripheral blood

T cell transfection: Transformed through genetic manipulation to express chimeric antigen receptor e.g. CD 19

T cell adoptive transfer: T cells reinfused into patient. These T cells then recognise disease (CD19 so recognising B cell malignancy)

Patient monitoring

Question 6

What is CML? [3]

Answer 6

Monogenic disease/single mutation

Philadelphia (ph) chromosome (9:22 translocation)

which encodes Bcr-Abl tyrosine-kinase

Question 7

What is the first line treatment for CML?

and describe its MOA

Answer 7

Imatinib

Starves Bcr-Abl of energy
Binds to ATP binding site
Switches off activity of this kinase

Question 8

Outline the mechanisms by which resistance to imatinib has developed

Answer 8

ABL kinase domain mutations - reduce binding efficacy of imatinib to ATP binding site
Increased amplification of BCR-ABL1 (multiple copies of gene in every cell)
Clonal evolution- tumour less reliant on activity of BCR-ABL1
Increased activity of drug efflux mechanisms (overexpression of P-gp substrate on surface leads to a reduction in the bioavailability of imatinib)

Question 9

What is leukamia?

Answer 9

• Failure of hematopoietic differentiation

- Results in accumulation of immature and/or dysfunctional leukocytes

Question 10

Why do patients with acute leukemia how low blood count?

Answer 10

differentiation arrests early in haematopoesis= immature leukocytes accum in bone marrow and remain here- pts present with low blood cell count

Question 11

What is CLL?

Answer 11

Clonal disorder of mature CD5+/CD19+ B cells

Question 12

What are some presenting features of CLL?

Answer 12

Enlarged lymph nodes
Repeat infections e.g. pneumonia and herpes
Abdominal discomfort
Night sweats and fever
Splenomegaly
Wt loss and muscle wastage
Anemia and/or bruising- suggesting retarded haematopoesis

Question 13

In CLL, what are the 3 mechanisms of actions of Targeted antibodies?

Answer 13

1. Complement mediated lysis (where Ab binds to cognate receptor which recruits complement to Ab leading to cell death)
2. Antibody dependent cytotoxicity- Ab binds to cognate receptor this flags to other cells like macrophages to induce response
3. Obinutuzumab- have direct cytotoxic effect of their own by bind to its receptor