immunotherap role of pharmacist...monitoring, evaluation, and education role of pharmacist slide # 2...
Post on 22-Sep-2020
1 Views
Preview:
TRANSCRIPT
Slide #Slide #
ImmunotherapyROLE OF PHARMACIST
1Pattariya Chantarasap, BCP, BCOP
Selection
Procurement
Prescribing, dosing, and transcribing
Storage
Preparing and dispensing
Administration
Monitoring, evaluation, and education
ROLE OF PHARMACIST
Slide #
2
2018 Nobel Prize in Medicine
Slide #
3
James P. Allison
Tasuku Honjo
Slide #
4
2019 Hematology/Oncology US FDA Approvals
CONCEPT
Slide #
6
HALLMARKS OF CANCER
Role of Immunotherapy
‣ Recognition of self
‣ Recognition of abnormal self
‣ Recognition of non-self
CONCEPT OF IMMUNE
Slide #
7
CELL INVOLVE
Slide #
8
Natural Killer Cell
IMMUNOTHERAPY IN CURRENT PRACTICE
Slide #
9
‣ Cytokines
‣ Cancer vaccines
‣ Adoptive Cell Therapy
‣ Check point inhibitors
IMMUNOTHERAPY IN CURRENT PRACTICE
Slide #
10
‣ Cytokines
‣ Cancer vaccines
‣ Adoptive Cell Therapy
‣ Check point inhibitors
Slide #
11Slide #
12SSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSSllllllllllllllllllllllllllllllllllllllllllllllllliiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiiddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddddeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeee ########################################################################
APPROVED AGENT
Slide #
13
‣ CTLA-4 inhibitor
‣ Ipilimumab
‣ PD1 inhibitor
‣ Nivolumab
‣ Pembrolizumab
‣ PD-L1 inhibitor
‣ Atezolizumab
‣ Avelumab
‣ Durvalumab
Slide #
14
IPILIMUMAB‣ A recombinant human immunoglobulin (Ig) G1
‣ Dose: 1 mg/kg or 3 mg/kg (depend on indication) q 3 wks for 4 dose, Molecular weight: 148000 dalton
‣ Half-life elimination: 15.4 days
‣ Clearance is increased with increasing body weight
‣ Administration via in-line filter (rate base on indicated dose)
‣ If concomitant with nivolumab: use separated filter and give nivolumab first
Slide #
15
NIVOLUMAB
‣ A recombinant human immunoglobulin (Ig) G4 monoclonal antibody
‣ Dose: 3 mg/kg, 240 mg q 2 wks, 480 mg q 4 wks
‣ Molecular weight: 143598 dalton
‣ Half-life elimination: 25 days
‣ Administration via in-line filter
Slide #
16
PEMBROLIZUMAB
‣ A recombinant human immunoglobulin (Ig) G4 monoclonal antibody
‣ Dose: 200 mg fixed dose or 2 mg/kg q 3 wks
‣ Molecular weight: 149000 dalton
‣ Half-life elimination: 22 days
‣ Administration via in-line filter
Slide #
17
ATEZOLIZUMAB
‣ A recombinant human immunoglobulin (Ig) G1 monoclonal antibody
‣ Dose: 1200 mg or 840 mg depend on indication
‣ Molecular weight: 145000 dalton
‣ Half-life elimination: 27 days
‣ Administration via in-line filter
lid # Slide #
18
DURVALUMAB
‣ A recombinant human immunoglobulin (Ig) G1 monoclonal antibody
‣ Dose: 10 mg/kg once every 2 weeks
‣ Molecular weight: 146300 dalton
‣ Half-life elimination: 18 days
‣ Administration via in-line filter
WHAT CHANGE
Slide #
19
‣ New and new concept of concomitant agents
‣ Difference toxic profile
‣ Longer duration of treatment
‣ New indications, including both solid and hematologic malignancy
‣ Financial burden
SYSTEMIC THRAPY
Slide #
20
ChemotherapyTargeted TherapyImmunotherapy
dddde #
ImmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmmuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuuunoooootttttttttttttttttttttttttttttttttttttttthhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhhheeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeerrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrraaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaappppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppppyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyyTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTTaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaaarrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrrggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggggeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeeetttttttted Therapy Chemotherapy
IMPOWER150 TRIAL
Slide #
21 N Engl J Med 2018; 378:2288-2301
IMPOWER150 TRIAL
Slide #
22
IMPOWER150 TRIAL
Slide #
23 N Engl J Med 2018; 378:2288-2301
IMPOWER150 TRIAL
Slide #
24 N Engl J Med 2018; 378:2288-2301
Slide #
25
WHY COMBINE
Slide #
26
LOOK FURTHER‣ VEGF-A inhibits maturation of dendritic cell,
which is antigen presenting cell (HPC)
‣ May also inhibits T cell by reducing
immigration of mature cell from thymus and
reducing cytotoxic activity
‣ May increases the levels of myeloid-derived
suppressor cell (MDSC)—>characterized by
their potent ability to suppress T and NK cell
along with promotion to regulation T cellCancer Microenvironment (2015) 8:15–21
27
WHAT CHANGE
Slide #
28
‣ New and new concept of concomitant agents
‣ Difference toxic profile
‣ Longer duration of treatment
‣ New indications, including both solid and hematologic malignancy
‣ Financial burden
Slide #
29
TIMING OF TOXICITY
Slide #
30
TIMING OF TOXICITY
J Clin Oncol 2012; 30:2691-7
Slide #
31
IMPOWER150 TRIAL
N Engl J Med 2018; 378:2288-2301
Slide #
32
IMPOWER150 TRIAL
N Engl J Med 2018; 378:2288-2301
WHAT CHANGE
Slide #
33
‣ New and new concept of concomitant agents
‣ Difference toxic profile
‣ Longer duration of treatment
‣ New indications, including both solid and hematologic malignancy
‣ Financial burden
CHECKMATE 067
Slide #
34 Lancet Oncol. 2018;19(11):1480-1492
CHECKMATE 067
Slide #
35 Lancet Oncol. 2018;19(11):1480-1492
CHECKMATE 067
Slide #
36 Lancet Oncol. 2018;19(11):1480-1492
CHECKMATE 067
Slide #
37 Lancet Oncol. 2018;19(11):1480-1492
‣ Duration of treatment (median)
‣ Ipilimumab plus nivolumab: nivolumab (IQR 2−32) and four
doses of ipilimumab (2−4);
‣ Nivolumab: 15 doses (IQR 6−54)
‣ Ilipimumab: 4 doses (IQR 2-4)
CHECKMATE 067
Slide #
38 Lancet Oncol. 2018;19(11):1480-1492
Slide #############################
ADVERSE EVENT
Slide #
39
‣ Fatigue is very common but normally mild
‣ Infusion-related reactions can occur (mostly are Grade 1)
ONSET & DURATION
Slide #
40
Example from Pool analysis: Safety Profile of Nivolumab Monotherapy
J Clin Oncol. 2017;35(7):785-792
ONSET & DURATION
Slide #
41 Eur J Cancer 2015; 51 (Suppl 3): S664–S665.
Slide #
Monotherapy VS Combination
MANAGEMENT
Slide #
42 Journal of Clinical Oncology. 2018) 1714-1768.
Ann Oncol (2017) 28 (suppl 4): iv119–iv142
GENERAL CONCEPT
Slide #
43
‣ Patient education
‣ Early detection and rule out other cause is the key
‣ High dose 0.5-2 mg/kg of steroid with slow taper over 4-6 wks is indicated in higher
grade adverse event
‣ Concurrent immunosuppressant maintenance therapy (10 mg prednisolone
equivalent dose) may be offered only if clinically indicated in individual cases
‣ Other agent e.g. Ifliximab, Mycophenolate may also indicated in refractory case
SKIN TOXICITIES
Slide #
44
‣ Incidence 30-50%
‣ Average onset 3-5 weeks
‣ Alopecia and mucositis can occur with incidence lower
than 10%
‣ Rare case for severe skin toxicities e.g. SJS, TEN was also
reported
SKIN TOXICITIES MANAGEMENT
Slide #
45
‣ ASCO guideline propose management paradigm according to type of rash
‣ Rash/inflammatory dermatitis
‣ Bullous dermatoses
‣ Severe cutaneous adverse reactions (SCARs), including SJS, TEN,
acute generalized exanthematous pustulosis, and DRESS/DIHS
SKIN TOXICITIES MANAGEMENT
Slide #
46
Slide #
47
SKIN TOXICITIES MANAGEMENT
Ann Oncol (2017) 28 (suppl 4): iv119–iv142
Slide #
48
SKIN TOXICITIES MANAGEMENT
Ann Oncol (2017) 28 (suppl 4): iv119–iv142
Slide #
49
BODY SURFACE AREA
Ann Oncol (2017) 28 (suppl 4): iv119–iv142
GI TOCIXITIES
Slide #
50
‣ Diarrhea
‣ Higher incidence in CTLA4 inhibitor (32-49%) when compare with PD1 and
PDL1inhibitor (1-40%)
‣ Average onset 6 weeks
‣ Colitis 8% to 16% in CTLA4 inhibitor and lower incidence (1-2%) in PD1 and
PDL1inhibitor
MANAGEMENT OF DIARRHEA
Slide #
51
Grading
G1: Increase of < 4 stools per day over baseline; mild increase in ostomy output
compared with baseline
Continue ICPi; alternatively, ICPi may be held temporarily and resumed if toxicity does not exceed G1
Monitor for dehydration and recommend dietary changes
Anti-motility agents e.g. loperamide can be helpful
Budesonide may be helpful in the early treatment of mild noninfectious diarrhea
Facilitate expedited phone contact with patient/caregiver
May obtain gastroenterology consult for prolonged G1 cases
Journal of Clinical Oncology. 2018) 1714-1768.
MANAGEMENT OF DIARRHEA
Slide #
52
Grading
G2: Increase of 4-6 stools per day over baseline; moderate increase in ostomy
output compared with baseline
Should hold ICPi temporarily until patient’s symptoms recover to G1; can consider permanently discontinuing CTLA-4 agents and may restart PD-1
May also include supportive care with medications such as Imodium
Administer corticosteroids, unless diarrhea is transient, starting with initial dose of 1 mg/kg/day prednisone or equivalent When symptoms improve to G1 or less, taper corticosteroids over at least 4-6 weeks
EGD/colonoscopy, endoscopy evaluation should be highly recommended to stratify patients for early treatment with infliximab
Stool inflammatory markers can be considered (lactoferrin and calprotectin)
Repeat colonoscopy is optionalfor disease activity monitoring to achieve complete remission, especially if there is a plan to resume ICPi
Journal of Clinical Oncology. 2018) 1714-1768.
MANAGEMENT OF DIARRHEA
Slide #
53
Grading
G3: Increase of 7 or more stools per day over baseline, incontinence, hospitalization
indicated, severe increase in ostomy output compared with baseline, limiting
self-care ADL
Should consider permanently discontinuing CTLA-4 agents and may restart PD-1, PD-L1 agents if patient can recover to G1 or less.
Administer corticosteroids (initial dose of 1-2 mg/kg/d prednisone or equivalent)
Consider hospitalization or outpatient facility for patients with dehydration or electrolyte imbalance
If symptoms persist 3-5 days or recur after improvement, consider administering IV corticosteroid or noncorticosteroid (eg, infliximab)
EGD/colonoscopy, endoscopy evaluation, and stool inflammatory marker
Consider colonoscopy in cases where patients have been on immunosuppression and may be at risk for opportunistic infections as an independent cause for diarrhea (ie, CMV colitis) and for those who are anti-TNF or corticosteroid refractory
Journal of Clinical Oncology. 2018) 1714-1768.
MANAGEMENT OF DIARRHEA
Slide #
54
Grading
G4: Life-threatening consequences; urgent intervention indicated
Permanently discontinue treatment
Should admit patient when clinically indicated; patients managed as outpatients should be very closely monitored
EGD/colonoscopy, endoscopy evaluation, and stool inflammatory marker
Administer 1-2 mg/kg/d methylprednisolone or equivalent until symptoms improve to G1, and then start taper over 4-6 weeks
Consider early infliximab 5-10 mg/kg if symptoms refractory to corticosteroid within 2-3 days
Consider lower GI endoscopy if symptoms are refractory despite treatment or there is concern of new infections
Journal of Clinical Oncology. 2018) 1714-1768.
MANAGEMENT OF DIARRHEA
Slide #
55
‣ Ifliximab dose: 5mg/kg every 2 weeks
‣ Mycophenolate (500-1000 mg bid) or vedolizumab may be indicated in ifliximab
refractory case
‣ No role of prophylactic with budesonide
Slide #
56
ESMO Guideline
ENDOCRINOPATHIES
Slide #
57
‣ Thyroid gland disorder is the most common
(higher incidence with hypothyroidism)
‣ Hyperthyroid is often transient and may precede
hypothyroidism
‣ Incidence of thyroid dysfunction requiring thyroid
hormone replacement was 21%
‣ More common with PD1/PDL1 when compare
with CTLA4 blocker
ENDOCRINOPATHIES
Slide #
58
‣ Thyroid gland disorder is the most common
(higher incidence with hypothyroidism)
‣ Hyperthyroid is often transient and may precede
hypothyroidism
‣ Incidence of thyroid dysfunction requiring thyroid
hormone replacement was 21%
‣ More common with PD1/PDL1 when compare
with CTLA4 blocker
MANAGEMENT OF THYROID DISORDER
Slide #
59
MANAGEMENT OF THYROID DISORDER
Slide #
60
Slide #
61
SPECIAL POPULATION
‣ IgG is known to cross the placenta and harm the fetus based on mechanism of action, reliable contraceptive is strongly recommended
‣ Ipilimumab: 3 months
‣ Nivolumab: 5 months
‣ Pembrolizumab: 4 months
‣ Durvalumab: 3 months
‣ Atezolizumab: 5 months
‣ Avelumab: 1 month
WHAT NEXT
Slide #
62
‣ More potential of check point target: BTLA,
VISTA, TIM3, LAG3, CD47, IDO
‣ Targeting on costimulatory receptors:4-1BB
(CD137): urelumab, OX40 (CD134)
Thank you
top related