Therapeutics Exam 2 Pt. 3 Liquid Cancers - Griffin Flashcards
Liquid Cancers:
seen in what 3 places..?
blood
bone marrow
lymph nodes
What cancers are apart of the myeloid cell lines
MDS - myelodysplastic syndrome
CML - chronic myeloid leukemia
AML - acute myeloid leukemia
What cancers are apart of the lymhoid cell lines
HD - hodkin lymphoma NHL - non-hodgkin lymphoma CLL - chronic lymphocytic leukemia ALL - acute lymphocytic leukemia MM - multiple myeloma
which cancer has reed sternberg cells?
hodgkin lymphoma
what is a reed sternberg cell
binucleated cell
what is lymphoma?
clonal disorder of HEMATOPOESIS involving malignant transformation of lymphocytes that predominate in the lymphatic system
Hodgkin Lymphoma- Etiology:
_______ giant cells that originate from _______
multinucleated giant cells
from B- lymphocytes
(aka Reed Sternberg cells)
Hodgkin Lymphoma:
Reed Sternberg cells overexpress _________
which leads to increased _______
and decreased _______
overexpress NFkB (nuclear factor Kappa B)
increased cell proliferation
decreased apoptosis
Hodgkin Lymphoma:
______ will upregulate NFkB
(up to 50% of hodking lymphoma cells are infected with ________)
infections will upregulate
EBV - epstein bar virus
Hodgkin Lymphoma - Clinical Presentation
Painless/rubbery - enlarged lymph node in _______ area
Mediastinal (around chest and sternum) involvement is common
______ manifestations are not common
_____ symptoms are 25 - 50 % common
in supradiaphragmatic area
Extranodal manifestations - not common
B symptoms
what are B symptoms?
fever greater than 38 degrees Drenching sweats (esp at night) Unintentional weight loss (> 10% over a period of 6 mos or less)
B symptoms - leads to better or worse overall prognosis?
worse
Hodgkin Lymphoma:
______ Staging - talks about how many lymph nodes are involved
Ann Arbor
Hodgkin Lymphoma: Ann Arbor Staging - Stage 1? 2? 3? 4?
1: involvement of one lymph node area
2: 2+ lymph node ares on SAME side of diaphragm
3: lymph node involvement on both sides
4: extranodal involvement (like bone marrow)
Hodgkin Lymphoma:
What does IPS stand for?
international prognostic score
score to see who is at poorer prognosis
Hodgkin Lymphoma:
what factors are seen to put someone at a poorer prognosis? (IPS factors!)
Albumin < 4 HgB < 10.5 Male stage IV 45 + y.o WBC > 15 Lymphocytopenia < 0.6
Hodgkin Lymphoma:
if they have ____ factors it is seen more as an unfavorable disease
2 + factors
Hodgkin Lymphoma:
What are some treatment modalities for this cancer?
RT (radiation therapy) Combo Chemo (ABVD!!!!, Standford V, BEACOPP)
or HD chemo with stem cell rescue
what does ABVD stand for?
doxorubicin (adriamycin!)
bleomycin
vinblastine
dacarbazine
Hodgkin Lymphoma:
for ABVD - how many cycles of it?
if stage I or II it is 4 cycles
if stage III or IV - then 6 cycles
Non-Hodgkin Lymphoma:
Symptoms are dependent on site of involvement:
if B cell lymphomas: _____, _____, _____ affected
it T cell lymphomas: ________ (_____ and _____)
Peripheral lymphadenopathy
40% of pts will have B symptoms
B cells: lymph nodes, spleen, bone marrow
T cells: extranodal sites (skin and lungs!)
Non-Hodgkin Lymphoma vs Hodgkin Lymphoma:
which one is more often localized to a single group of nodes?
Hodgkin
Non-Hodgkin Lymphoma vs Hodgkin Lymphoma:
has a noncontagious spread (aka a variety of lymph nodes are affected)
non-hodgkin lymphoma
Non-Hodgkin Lymphoma vs Hodgkin Lymphoma:
which one has more frequent involvement of multiple peripheral nodes?
Non-Hodgkin Lymphoma
Non-Hodgkin Lymphoma vs Hodgkin Lymphoma:
which one will orderly spread by contiguity?
aka spread to close lymph nodes first)
hodgkin
Non-Hodgkin Lymphoma vs Hodgkin Lymphoma:
which one will commonly have extranodal presentation?
non-hodkgin
hodgkin will rarely have extranodal involvement!!
Non-Hodgkin Lymphoma vs Hodgkin Lymphoma:
which one will commonly have mesenteric nodes and waldeyer ring?
non-hodgkin
hodgkin will rarely have mesenteric or waldeyer ring!
what is the most common B cell lymphoma?
diffuse large B cell
what B cell lymphoma is “indolent”
aka has a relatively long survival and usually incurable?
follicular B cell lymphoma
what B cell lymphoma is “aggressive”
aka rapid growth and short survival if untreated and usually curable
diffuse large B cell
what B cell lymphoma is “highly aggressive”
aka has a doubling time around 18 h!! but also usuall curable bc super sensitive to chemo
burkitt B cell lymphoma
and AIDS related b cell lymphoma
T or F: lymphomas are steroid sensitive
TRUE!
why R-CHOP has prednisone!
R-CHOP is big with diffuse large B cell
what does R-CHOP mean?
R- Ritxuimab C - Cyclophosphamide H - doxorubicin O - vincristine P - prednisone
why is rituximab good for B - cell lymphomas?
it targets CD-20! found on B cells…
when R-CHOP used?
when B cells lymphomas - part of non hodgkins lymphoma
Folliclular lymphoma:
use ______ to gauge risk factors
FLIPI (follicular lymphoma international prognostic index)
what are 1st line therapy options for follicular lymphoma?
bendamustine + rituximab (good if pt is good performance status!! - this is the BEST OPTION!)
R-CHOP
R-CVP
Rituximab (preferred if pt is elderly)
what does R-CVP stand for and when is it used?
R - rituximab C - cyclophosphamide V - vincristine P- prednisone *used for non-hodgkin lymphoma -- follicular lymphoma (same as R-CHOP but no doxorubicin!)
what is richters syndrome?
when indolent lymphoma (ex: follicular) transforms into more aggressive lymphoma
treatment options for richters syndrome?
doxorubicin based chemo w/ rituximab
Burkitt Lymphoma:
(mild or aggressive?)
Translocation involving ______ gene detected in nearly all cases
MYC gene
bone marrow in burkitt lymphoma looks like ______
starry sky
??
what are the FDA approved products for T - Cell immunology
Tisagenlecleucel (Kymriah)
or
Axicabtagebe ciloleucel (yescarta)
AIDS Related lymphoma:
Occurs (early or late) in HIV infection
Most AIDS related lymphomas are ____ neoplasms
late
B - cell (DLBCL or burkitt)
what is DLBCL mean?
difuse large B cell lymphoma
Treatment considerations of AIDS related lymphoma:
Most pts present with ______ and advanced disease
Concurrent ____ is assoc w/ higher complete remission rates
______ for all pts
_______ chemo for prophylaxis
present w/ B symptoms
concurrent HAART
G-CSF for all pts
intrathecal chemo
Lymphoma Summary: Treat with multi agent chemo = 5 yo overall survival what chemos are best? Hodgkin: \_\_\_\_\_\_ Non-Hodgkin: \_\_\_\_\_\_
Hodgkin: ABVD
Non-Hodgkin: R-CHOP
what is MM?
multiple myeloma
a progressive B cell disorder
Multiple Myeloma:
Typically have ____ symptoms
CRAB
what are CRAB symptoms for Multiple Myeloma?
C - Calcium corrected > 11 (albumin - for correction)
R renal dysfunction SCr > 2 or CrCl < 40
Anemia < 10 or 2 below normal
Bone - 1+ osteolytic lesions or pathologic fractures
Multiple Myeloma:
T or F: it has a very high cure rate
false
remains an incurable malignancy
Progression of Multiple Myeloma (?)
the flow chart of multiple myeloma
MGUS (monoclonal gammopathy of undetermined significance) –> Bone marrow increased angiogenesis –> lytic bone lesions –> plasma cells in blood
some other signs/symptoms of multiple myeloma outside of CRAB symptoms?
EMPs (extramedullary plasmacytomas) - plasma cell tumors arise outside the bone marrow
increased susceptibility of infections
Hyperviscosity (blood too thick b/c of myeloma proteins) (HA, blurred vision, oral bleeding etc)
what are the 3 phases of therapy for multiple myeloma
induction therapy
consolidation therapy
maintenance therapy
Multiple Myeloma - Induction Therapy: # drug regimens are preferred over # drug regimens
3 preferred over 2
if pt could tolerate 3 then do it!
Multiple Myeloma - Induction Therapy:
is the patient a ________ candidate - if so do _____ after the 3 drug regimen
potential transplant candidate?
do a stem cell harvest (do after 3 - 4 cycles of induction) - dont wait too long because then none will be there
what are some common Multiple Myeloma - Induction Therapy options
ALL ARE BORTEZOMIB BASED
(VRD) bortezomib/lenalidomide/dexamethasone
(CyBorD) bortezomib/cyclophosphomide/dexamethasone
bortezomib/doxarubicin/dexamethasone
what are common agents used in multiple myeloma (induction therapy)
(6 total)
Steroids IMiDs (immunomodulatory drugs) Proteasome Inhibitors Traditional Chemo (doxarubicin and cyclophosphamide) Monoclonal Abs Histone Deacteylase inhibitors
what drugs are IMiDs?
thalidomide, lenalidomide, pomalidomide (REMS program!!)
what drugs are proteosome inhibitors?
bortezomib, carfilzomib, ixazomib
what are some monoclonal antibodies used in multiple myeloma (induction therapy)
daratumumab
elotuzumab
what are some histone deacteylase inhibitor used in multiple myeloma (induction therapy)
panobinostat
Bortezomib based regimens usually have a significant comorbidity of _____
PN (peripheral neuropathy)
what is SCT
stem cell transplant
Who can get a SCT? (stem cell transplant)
____ is not a limiting factor
but
______ limits pts from becoming a SCT canidate
age is not
poor performance status will prevent candidacy
what was found to decrease rates of PN (peripheral neuropathy)
(dosing frequency, route etc)
*I think PN rates of the -zomibs..?
SQ admin decreased rates of PN
Weekly dosing instead of twice weekly still had same rate but there was less discontinuation — so in long run pts rcvd more of the dose
Stem cell transplant before or after CR (complete remission) is the better/superior outcome
SCT after CR!!
clear it out then give whole new system
Daratumumab targets _____ and is used in ______
CD-38
used in multiple myeloma
Common Complications of multiple myeloma?
bony manifestations
herpes zoster
thromboembolism risk
Common Complications of multiple myeloma:
How to treat bony manifestations…
bisphosphonates! (pamidronate and zoledronic acid)
use these for 2 years
Common Complications of multiple myeloma:
Treating bony manifestations —
monitor _____ and ______
and supplement ____
monitor renal function and osteonecrosis
pts should get 500 mg Ca2+ and 500 units of Vit. D
Common Complications of multiple myeloma:
People can get herpes zoster how?
pts on proteasome inhibitor or monoclonal antibody are at increased risk of HSV infections
Common Complications of multiple myeloma:
How to decrease chance of HSV infections
prophylactically treat with acyclovir and valacyclovir
Common Complications of multiple myeloma:
what drugs increase risk of thromboembolism?
IMiDs and Dexamethasome regimens increase VTE risk
Common Complications of multiple myeloma:
What to do to decrease thromboembolism risk with IMiD/dexamethasone regimens?
give ASA! or warfarin or enoxaparin… just give VTE crap
CML (chronic myleoid leukemia)
genetics behind it?
Philadelphia Chromosome (BCR- ABL)
how can you cure CML?
allogenic hematopoeitic stem cell transplantation (HSCT)
what drug class is used in CML
TKI’s (tyrosine kinase inhibitor)
what drugs are TKI’s used for CML
imatinib nilotinib (2nd gen) dasatinib (2nd gen) bosutinib (2nd gen) ponatinib (3rd gen)
which TKI’s produced a faster/deeper response in CML
nilotinib and dasatinib
CML:
only one TKI is BID - which one?
Nilotinib
CML:
which one must be taken with an empty stomach
Nilotinib
CML:
main issues with TKIs?
DRUG INTERACTIONS CYP3A4 wit all
P-Gp for some
Main Side Effect of Imatinib?
Nausea
Main Side Effect of Dasatinib?
Fluid retention (pleural effusion)
Main Side Effect of Nilotinib?
QTc prolongation
metabolic syndrome
Main Side Effect of Bosutinib?
diarrhea
Main Side Effect of Ponatinib
Ischemic reactions
Vascular occlusion
HTN
** huge in picking what therapy ppl can use!!!
BCR-ABL can have resistance/a mutation that prevents normal TKI’s to be effective
what is the mutation and what drug overcomes it?
T3151
Ponatinib
T or F: For 2nd line tx of CML - you can increase the imatinib doses and the 2nd gen doses
FALSE
can increase imatinib
but do NOT dose increase the 2nd gens
T or F: since ponatanib is effective with the “gate keeper” mutation - it should be used 1st line
FALSE! only do it if mutation or failed other options – severe ADE’s so save it
what is another drug for CML that tackle the T3151 mutation
Omacetaxine
what are different phases of CML?
Chronic (most common)
accelerated
or Blast
Goal is to get pts with CML to the ____ phase
chronic (not accelerated or blast)
CLL (chronic lymphoblastic leukemia) - genetics:
which mutation leads to the biggest decrease in survival ?
deletion 17p
why is the loss of 17p in CLL so devastating?
it reflects the loss of the key tumor supressor TP53
CLL -
treatment usually done for what pts? (what staging)
only treat stages III/IV or those that are symptomatic
what is first line tx for CLL pts - IF Young and Fit (<65 and no comorbidities)
if no del 17 or TP53 mutation - give what?
give FCR!!!
FCR = fludrabine
cyclophosphamide
rituximab
or maybe ibrutinib
what is first line tx for CLL pts - old and Fit (>65 and no comorbidities)
w/ no del17/TP53 mutation
obinutuzumab + chlorambucil
or ibrutinib (good option for old ppl who cant tolerate FCR)
what is first line tx for CLL pts - for frail pts?
w/ no del17/TP53 mutation
obinutuzumab + chlorambucil
or ibrutinib (good option for old ppl who cant tolerate FCR)
what is first line tx for CLL pts?
w/ the del17/TP53 mutation!!
Ibrutinib
HDMP + Rituximab
Alemtuzumab +/- Rituximab
what are some of the 2nd line CLL options?
Ventetoclax
Ibrutinib
Idealisib
MOA of ventetoclax?
B -cell receptor inhibitor
Venetoclax ADEs?
Tumor lysis syndrome Cytopenia N/V HA Upper respiratory infections
T or F: Venetoclax is best in combo therapy
TRUE — do not use this drug as mono therapy
Ibrutinib ADEs?
transient lymphocytosis!!! (may look like failing therapy but nah - the drug is working!)
bleeding events!
A.fib
diarrhea
Idelalisib ADEs?
transient lymphocytosis!!! (may look like failing therapy but nah - the drug is working!)
Increases LFTs
Diarrhea/Colitis - maybe treat w/ corticosteroids
how to combat the transient lymphocytosis seen with idelalisib
give rituximab with it
The lymphocytosis seen from Idelalisib and ibrutinib resolves by _____
and remember this transient increase in absolute ______ count does NOT signify disease progression
resolves by week 12
absolute lymphocyte count
what does MDS stand for
myelodysplastic syndrome
MDS has the potential to evolve into _____
we want to precent this evolution!!
AML
diagnosing of MDS:
stable _____ for at least 6 mos
Specific MDS associated karyotype (____)
cytopenia
del5q
MDS clinical presentation?
Since Cytopenia…. what symptoms will see what?
Cytopenia = low WBCs, platelets, RBCs –>
Fatigue/malaise/dyspnea on exertion (low RBCs)
cough/dysurea (low WBCs)
bleeding/bruising easily (low platelets)
what are the main therapeutic options for MDS?
supportive care
low intensity therapy
high intensity therapy
enrollment in a clinical trial
what are some supportive care options for MDS
blood product transfusions growth factor support EPO stimulating agents TPO receptor agonists Managing iron overload (esp w/ frequent transfusions)
MDS Treatment Options: If a pt is to get low intensity therapy:
if pt has Del5q - give them ______
if pt has low sEPO give them ______
if pt has normal - high sEPO give them _____ and ______
Del5q- Lenalidomide
low sEPO - ESA
Normal-High EPO: give IST (immuno- suppresive therapy) and 2nd line?? - hypoalkylating agents
________ is the drug used when MDS pts have a del5q chromosome abnormality
lenalidomide
it causes apoptosis!
MDS Treatment: Low Intensity Therapy
Immunosuppresive therapy goal: ______
ESA goal: ___________
IST: mitigate bone marrow failure
ESA: reduce symptoms of anemia and allow for transfusion independence
MDS Treatment: Low Intensity Therapy
Response seen after how long of therapy?
Immunosuppresive therapy: _______
ESA therapy: _________
IST: 4 - 6 mos!!! ahhh so long
ESA: 6 - 8 weeks
MDS Treatment: HIgh Intensity Therapy
what are the 2 options?
intensive AML chemo –> stem cell transplant
or
hypo-methylatying agents!
what drugs are a part of immunosuppresive therapy in MDS
cyclosporine
antithymocyte globulin
what drugs are hypo-methylatying agents
azacitidine
decitabine
DNA methylation leads to the tumor suppressor gene becoming _____
silenced!
why HYPOalkylating agents = tumor suppressor gene is active
MDS Summary:
Use low intensity therapy when ________
use high intensity therapy when ________
low: treat symptoms
high: prevent transformation to AML
AML?
acute myeloid leukemia
what gene mutation is seen as very unfavorable in AML
FLT3
what drug was recently approved for FLT3 mutation in AML
midosautrin
Secondary AML is common with what agents?
Alkylating agents
TOPO II inhibitors
Treatment for AML
1) _______ Goal is remission
2) ______ goal is prevent relapse
3) ______ prevent relapse if high risk
1 - induction
2- consolidation
3 - transplant
AML Tx:
Intensive therapy? (what drugs)
Goal = complete remission
cytarabine and an anthracycline
7 + 3 chemo!!!
all 7 days get cytarabine
first 3 you get anthracycline (with cytarabine)
what are some high dose toxicities of cytarabine?
cerebellar side effects (look drunk..)
and
CHEMICAL CONJUCTIVITIS!!
what is a good drug therapy to go with HD cytarabine?
eye drops!! (steroid or natural eyes)
HD cytarabine leads to chemical conjuctivtis
what is the one way to cure AML
stem cell transplant
APL is a type of ______
it is key to know the differences because it needs to be treated fast….?
type of AML
it is the better one to have
APL:
there is a ______ of chromosomes 15/17 which is apart of the ______ receptor
translocation
retinoic acid receptor
All-trans retinoic acid
ex: _______
effective in AML/APL because it disrupts the binding of _______ and restores normal _____/______ pathway
ex: trentinoin
disrupts gene repressor binding
normal maturation/differentiation pathway
AML diagnosis based on _________ biopsy
bone marrow
ALL -
what drug classes are staples for treatment
steroid
vinca alkaloid
antrhacycline
25% of Adult ALL patients will have ______ positive disease and adding ________ inhibitors to multiagent chemo is best
Philadelphia positive disease (BCR-ABL!!!)
adding TKIs
MOA of Blinatumomab and what cancer may it be used in
MOA: bispecific T cell engaged (CD19 and CD3)
ALL cancer (used 2nd line)
black box warnings of blinatumomab?
cytokine release syndrome
neurotoxicity
ALL:
______ plays a large role in overall prognosis
_________ plays a large role in treatment
Risk stratification
Maintenance therapy
Definitions:
Autologous Transplant
pt serves as own donor
Definitions:
Engraftment
blood cell recovery after transplant
Definitions:
Allogeneic transplant
matched sibling or unrelated donor
Definitions:
conditioning regimen
chemo/radiation given prior to stem cell infusion
Definitions:
stem cell mobilization
process of collecting stem cells
what type of SCT is common for AML cancer
allogenic
what type of SCT is most common in the US
autologous
For allogenic transplant: ______ matching is key
HLA (human leukocyte antigens)
HLA is encoded by genes of the _____ which is located on chromosome 6 (the major function is regulation of __________)
genes of NHC (major histocompatibility complex)
major function is immune responsiveness
what are the main sources of donor cells for SCT?
bone marrow
peripheral blood
umbilical cord blood
Donor Cell Source: Bone marrow, peripheral blood, or umbilical cord blood?
invasive procedure/large volume collected/LONGER TIME TO ENGRAFT
bone marrow
Donor Cell Source: Bone marrow, peripheral blood, or umbilical cord blood?
small volume collected/faster engrafment/may require multiple sessions
peripheral
Stem cell mobilization must happen because there is not enough stem cells in peripheral blood – thus give ______
give growth factors (filgrastim +/-perixafor)
If a healthy pt gets filgrastim – what will they typically complain of?
bone pain
what is the main difference in the process of autologous and allogenic stem cell transplants?
must start immunosupression before giving stem cells in allogeneic
radiation may be used in combo with chemo prior to SCT —- this is helpful when the tumor cells are hard to reach with chemo — what are examples of this?
CNS and testes
what does TBI stand for
total body irradiation
Per Griffin Lecture: NON-hematologic dose limiting toxicities table:
Cyclophosphamide?
cardiomyopathy
Per Griffin Lecture: NON-hematologic dose limiting toxicities table:
melphalan
mucositis
Per Griffin Lecture: NON-hematologic dose limiting toxicities table:
busulfan
hepatic
Per Griffin Lecture: NON-hematologic dose limiting toxicities table:
TBI
pulmonary
Per Griffin Lecture: NON-hematologic dose limiting toxicities table:
Carboplatin
hepatic/renal
Per Griffin Lecture: NON-hematologic dose limiting toxicities table:
etoposide
mucositis
Per Griffin Lecture: NON-hematologic dose limiting toxicities table:
carmustine
hepatic/pulmonary
what does MAC mean?
myeloablative conditioning (AKA take out allllll of bone marrow - and must rescue with stem cells)
what is RIC and when is it used?
RIC = reduced intensity conditioning
(also known as non-myleoablative conditioning)
use when pts probably wont be able to tolerate allogeneic SCT…
what are some common myeloablative conditioning regimens?
busulfan and cyclophosphamide (BuCy)
cyclophosphamide and TBI (Cy/TBI)
Engraftment occurs when
_____ and _____ are above certain levels 3 days in a row
_____ and _____ take hella lot longer to get back to normal
neutrophils and platelets
lymphocytes and erthocytes
Transplant related complications?
what is seen post transplant
infections
graft vs host disease
organ dysfunction
Transplant related complications?
what is seen peri transplant
peri = about/around infections N/V/D mucositis graft failure organ dysfunction
Acute vs chronic GVHD: how many days to be considered each?
< 100 days post SCT = acute
> 100 days post SCT = chronic
how to treat both acute or chronic GVHD
steroids
Grading Acute GVHD – looking at what 3 different things?
skin
liver
intestinal tract
Counseling points related to SCT
- Good _______ and limit________
- Minimal contact with recipients of _________ for 4 weeks
- SCT pts require _______ over 1 - 2 year period post transplant
- good hand hygiene/ limit sick contact
- avoid recipients of live vaccines for 4 weeks
- require re-immunization over 1 - 2 year period (like childhood vaccines!)
Late complications of SCT? \_\_\_\_\_\_\_\_\_\_\_ disease \_\_\_\_\_\_\_\_ disease \_\_\_\_\_\_\_\_ formation \_\_\_\_\_\_\_\_ dysfunction and \_\_\_\_\_\_ \_\_\_\_\_\_\_\_\_ disease \_\_\_\_\_\_\_\_\_\_\_\_\_
restrictive and obstructive pulmonary disease bone/joint disease cataract formation thyroid dysfunction/sterility Cardiovascular disease Secondary malignancies
