New and future treatments for blood cancers Flashcards
Why do lymphoma, CLL and acute ;leukaemia respond well to chemo and radiotherapy?
- lymphocytes are keen to undergo apoptosis in the normal lymph node
- Lymphoma and CLL cells can be triggered to undergo apoptosis readily with chemo or RT
- acute leukaemia is dividing quickly- more cells affected by chemotherapy
SE of chemo and radiotherapy
- why do these occur?
- immediate effet?
- long term effect?
-normal cells have DNA damage and undergo apoptosis
-hair loss, nausea & vomiting, neutropenic infection
Tiredness+++
-heart damage, lung damage, other cancers
Supportive therapy in chemo
state the measures taken:
-to prevent infection
-to reduce fatigue
- prompt treatment of neutropenic infection/fever
broad spec antibiotics
Growth factors
Prophylactic antibiotics & antifungals (ciprofloxacin)
-Red cell and platelet transfusion
Describe the course of action in a patient presenting with neutropenic fever?
-antibiotic therapy in standard and high risk patients?
Asses patient within 15 mins
Provide antibiotics within 1 hour
full infection screen
-standard risk patient (neutropenia + sepsis +SEWS < 6)
Start Piperacillin/Tazobactam within 1 hr
High risk patient
(neutropenia + severe sepsis/septic shock or SEWS > 6)
start piperacillin/tazobactam + gentamicin
what is given to prevent fungal infections?
itraconazole or posaconazole
What is behind the idea of risk adapted therapy?
can increase the doses in those who need to for cure and reduce or miss out chemo and radio in those who don’t need it to avoid long term SEs
name the 3 different kinds of targeted therapy?
monoclonal antibodies
biological agents
Molecularly targeted treatments
Monoclonal antibodies
-how do they work?
-affect only cells which posses target protein however current;y used in combination with chemo rather than instead of but more effective than chemo alone
Rituximab
- what is it?
- describe the structure?
- indicated in what?
-mouse/human chimeric MoAb
-murine variable regions which bind specifically to CD20 on B cells
human Kappa constant regions
human IgG Fc domain works in synergy with human effector mechanisms
naked antibody so can attach on chemo drugs etc.
-B cell non hodgekins lymphoma
CLL
mantle cell NHL
Anti-B cell antibodies
-advantages over rituximab?
More direct kill of malignant B cells, use if patient not responding to rituximab
Brentuximab Vedotin
- used in what condition?
- how does it work?
-Hodgkin’s disease
-CD30 protein present on hodgkin’s cells and some T cell NHL
chemo drug is conjugated on providing target chemotherapy
Biological treatments
- general action?
- exapmples?
- indications?
not chemo so don’t affect cells as they divide however there are a variety of modes of action
Se as not targeted
- proteosome inhibitors and IMIDs
- Multiple myeloma and lymphoma
Proteosome inhibitors
- purpose of proteosome?
- mode of action?
- indications?
- SE?
-dustbin for old proteins inside cells
breaks them done into amino acids
-blocking allows accumulation of toxic proteins in cell causing apoptosis
-mantle cell NHL
low grade NHL
-nerve damage and thrombocytopenia
IMIDs
- derived from what?
- example?
- mechanism of action?
- indications?
- SE?
- Derivative of thalidomide,
- Revlamid
- blocks IL 6, disimpairment of angiogenesis so myeloma cells starved of blood
- low grade NHL and CLL Myeloma
-risk to foetus
effects blood count- fatigue
other cancers
neuropathy
Molecular/targeted treatment
- must fit 3 criteria?
- examples? (3)
-Target pathway specific to the cancer cell
avoid SE
more effective than them
-tyrosine kinase inhibitors in Chronic myeloid leukaemia
Ibrutinib- CLL/NHL
Nivolumab helps prevent tumour evasion
Tyrosine Kinase inhibitors
- what causes CML?
- give an example?
- SE?
- a chromosomal translocation to produce the philidelphia chromosome- BCR-ABL gene, activity of this gene stimulates rapid proliferation via tyrosine kinase action
- Imatinib
- diarrhoea, plural effusion, neutropenia
Drugs affecting B cell signalling pathways
- premise of action?
- give examples?
- indications?
- SE’s?
- CLL and lymphoma cells have abnormally active signalling mechanisms inside cells blockage of these signalling proteins can cause apoptosis if P53 is abnormal
- Ibrutinib and Idelalisib
- low grade NHL and B cell CLLnot responding to retuximab and chemo
-Ibrutinib
(fever, low platelets, anaemia, SOB)
Idelalisib
(Diarrhoea, rash, fatigue, liver abnormality, fever)
Checkpoint inhibitors
- example of these drugs and mode of action?
- explain how immune evasion occurs?
- SEs?
- Nivolumab
used in malignant melanoma sticks to PD-1 receptor chemicals and stops it binding to effector cells- immune system stays switched on and attacks cancer cell
-the cancer cells produce chemicals that bind to receptors on surface of cells of the immune system called PD-1
when the receptor cell is stimulated the immune system cell is switched off and ignores the tumour
-long list, rash, dec platelet count, fatigue
Immune therapy
- describe what this is?
- detrimental effects?management?
-allogenic BM transplant from a matched donor
T cells from the donor cause immune attack on cancer
Graft Vs Leukaemia/Lymphoma effect
- immune attack of normal cells in Graft VS host disease
can give steroids but risk of malignancy returning
Adaptive immunotherapy
- what is this?
- an example of this?
when you make the patients own immune cells recognise the cancer as foreign and attack it
-Chimeric Antigen Receptor (CAR) T cells
These are the patients own T cells removed by leukophoresis that have been genetically modified to target a specific type of cancer
give Chemo first to prevent rejection
