Advancements in Treatment of Malignancy

Question 1

How have advancements in treatment improved prognosis of haematological malignancies?

Answer 1

60-70% of high grade B cell-NHL are cured

Average lifespan after diagnosis with low grade NHL is almost 20 years

Question 2

What is the supportive therapy for haematological malignancy?

Answer 2

Prompt treatment of neutropenic fever/infection = broad spectrum antibiotics
Red cell and platelet transfusion
Growth factors
Prophylactic antibiotics and antifungals

Question 3

How is chemo/radiotherapy delivery optimised?

Answer 3

Increase dose when needed and accept side effects

Reduce chemotherapy or miss out radiotherapy in those who don’t need it to avoid long term side effects

Question 4

How are PET scans used to guide treatment of Hodgkin’s lymphoma?

Answer 4

Used to guide chemo/radiotherapy = relapse likely if PET positive after 2 out of 6 courses of ABVD

Question 5

What are some examples of targeted therapies?

Answer 5

Monoclonal antibodies, biologics, molecular treatments

Question 6

What are the benefits of monoclonal antibodies?

Answer 6

Immune treatment so only affect cells which possess target protein = avoids side effects
More effective than chemo alone when used alongside chemo

Question 7

What is rituximab?

Answer 7

Mouse/human chimeric monoclonal antibody

Question 8

What is the target of rituximab?

Answer 8

CD20 = murine variable region of antibody binds specifically to CD20 on B cells

Question 9

What is the purpose of the human IgG1Fc domain on rituximab?

Answer 9

Works in synergy with human effector mechanisms

Question 10

How is rituximab given?

Answer 10

As a 5 minute injection under the skin

Question 11

What are the benefits of rituximab?

Answer 11

Improves survival in low grade and mantle cell NHL
FCR improves survival in CLL
RCHOP cures high grade B cell NHL

Question 12

What are some examples of B cell monoclonal antibodies?

Answer 12

Rituximab, obinutumab, ofatumunab

Question 13

What are the benefits of obinutumab and ofatumunab?

Answer 13

More direct kill of malignant B cells that rituximab

Better in CLL in less fit patients when used with gentle chemo

Question 14

When are obinutumab and ofatumunab mainly used?

Answer 14

Mainly used in patients not responding to rituximab

Question 15

What is brentuximab vedotin?

Answer 15

Anti-CD30 antibody with chemotherapy conjugated on = target’s Hodgkin’s cells and some T cell NHL

Question 16

What is the action of biologics?

Answer 16

Don’t affect cells as they divide and cause side effects as they aren’t targeted to malignant cells

Question 17

When are biologics used?

Answer 17

To treat multiple myeloma

Question 18

What are the two most commonly used biologic therapies?

Answer 18

Proteosome inhibitors and IMIDs

Question 19

What is the action of proteosome inhibitors?

Answer 19

Block breakdown of old proteins in cell causing apoptosis via the accumulation of toxic proteins

Question 20

What are the uses of proteosome inhibitors?

Answer 20

Boretezomib has some effect in mantle cell NHL

Used in some low grade NHL

Question 21

What are the side effects of proteosome inhibitors?

Answer 21

Nerve damage and low platelets

Question 22

What is the use of IMIDs?

Answer 22

Treat myeloma and other plasma cell disorders

Question 23

What are some examples of IMIDs?

Answer 23

Lenalidomide and pomalidomide have less side effects than thalidomide

Question 24

What is an example of a molecular treatment of haematological malignancy?

Answer 24

Tyrosine kinase inhibitors = imatinib, nilotinib, bosutinib

Question 25

What are the benefits of tyrosine kinase inhibitors?

Answer 25

Generally well tolerated and achieve remission in most with CML

Question 26

What type of therapy is an allogenic bone marrow transplant?

Answer 26

Immune therapy

Question 27

What is a complication of an allogenic bone marrow transplant?

Answer 27

T cells from donor can cause immune attack = graft vs leukaemia/lymphoma (GvL), graft vs host disease (GvHD)

Question 28

What is the purpose of adaptive immunotherapy?

Answer 28

Makes the patient’s own immune cells recognise cancer as foreign and attack it = avoids GvHD

Question 29

What is an example of an adaptive immunotherapy?

Answer 29

CAR-T cell therapy = used for high grade B cell NHL and refractory B cell ALL in patients up to age 25