Immunotherapy in cancer

1. IMMUNOTHERAPY IN
CANCER
Dr. Srujana Joga
Moderator : Dr. Parveen Jain

2. HISTORY
• Paul Ehrlich first conceived the idea that tumor cells can be
recognized as “foreign” and eliminated by the immune system.
• Subsequently, Lewis Thomas and Macfarlane Burnet formalized this
concept by coining the term immune surveillance, which implies that
a normal function of the immune system is to constantly “scan” the
body for emerging malignant cells and destroy them.

3. Cancer Immunoediting
• The fact that cancers occur in immunocompetent individuals
indicates that immune surveillance is imperfect
Reason: invisible to the host immune system or
release factors that actively suppress host immunity.
• The term cancer immunoediting has been used
= the ability of the immune system to shape and mould the immunogenic properties of tumor cells
in a fashion that ultimately leads to the darwinian selection of subclones that are best able to avoid
immune elimination.

12. Cross-presentation of tumor antigens

20. • Active: Induced Directly in the Patient
Can be Specific or Non Specific
• Passive or Adoptive: Immunologically active material transferred into
patient
Specific (Antibodies, T-Cells, Antigen-presenting cells – Dendritic Cell
Vaccines) Or
Non-Specific (Non-specifically-activated T-Cells; Cytokines)

21. Passive/Adoptive Immunotherapy of Cancers
• Non-Specific:
Lymphokine-activated Killer Cells (LAK Cells)
Cytokines (TNF alpha; IL2; Interferon)
• Specific:
Molecular Transfer - Monoclonal Antibodies (antibodies are specific)
Cellular Transfer (antigen-specific)
Tumor-Infiltrating Lymphocytes (TIL Cells)
Engineered Antigen-Presenting Cells (Dendritic Cells)

31. minimum 100 viable tumor cells

32. • PD-L1 IHC 22C3 pharmDx by Dako
• PD-L1 IHC 28–8 pharmDx by Dako
• VENTANA PD-L1 (SP263) Rabbit Monoclonal Primary Antibody by
Roche
• VENTANA PD-L1 (SP142) Assay by Roche
• PD-L1 (E1L3N®) XP® Rabbit mAb #13684

60. NIVOLUMAB
• human monoclonal antibody that blocks the interaction between PD-
1 and its ligands, PD-L1 and PD-L2
• It is an IgG4 kappa immunoglobulin that has a calculated molecular
mass of 146 kDa.
• It is expressed in a recombinant Chinese Hamster Ovary (CHO) cell
line.
• Injection:
40 mg/4 mL, 100 mg/10 mL, and 240 mg/24 mL solution in a single-
dose vial

61. Pharmacokinetics:
mean elimination half-life (t1/2) is 25 days
clearance increases by 24% when given with ipilimumab
Adverse Effects (≥20%)
• single agent:
fatigue, rash, musculoskeletal pain, pruritus, diarrhea, nausea, asthenia,
cough, dyspnea, constipation, decreased appetite, back pain, arthralgia,
upper respiratory tract infection, pyrexia, headache, and abdominal pain.
• with ipilimumab:
fatigue, rash, diarrhea, nausea, pyrexia, vomiting, and dyspnea

62. INDICATIONS
Dose: 240 mg every 2 weeks.
• Unresectable or metastatic melanoma
Nivolumab with ipilimumab: Nivolumab 1 mg/kg, followed by ipilimumab on the same day, every
3 weeks for 4 doses, then nivolumab 240 mg every 2 weeks.
• Adjuvant treatment of melanoma
• Metastatic NSCLC
• Advanced renal cell carcinoma with prior anti-angiogenic therapy
• Classical Hodgkin lymphoma
3 mg/kg every 2 weeks
relapsed or progressed after:
- autologous hematopoietic stem cell transplantation (HSCT) and brentuximab vedotin, or
- 3 or more lines of systemic therapy that includes autologous HSCT.

63. • Recurrent or metastatic SCC of the head and neck
with disease progression on or after platinum-based therapy
3mg/kg every 2 weeks
• Locally advanced or metastatic urothelial carcinoma
- disease progression during or following platinum-containing
chemotherapy
- disease progression within 12 months of neoadjuvant or adjuvant
treatment with platinum-containing chemotherapy
• Microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)
metastatic colorectal cancer
• Hepatocellular carcinoma

64. Preparation and Administration
• a clear to opalescent, colorless to pale-yellow solution
• Discard the vial if the solution is cloudy, discolored, or contains
extraneous particulate matter other than a few translucent-to-white,
proteinaceous particles.
• Do not shake the vial
Preparation
Dilute with either 0.9% NS or 5% Dextrose to prepare an infusion with
a final concentration ranging from 1 mg/mL to 10 mg/mL
Mix diluted solution by gentle inversion. Do not shake
Discard partially used vials

65. Storage from the time of preparation
• at room temperature for <= 8 hours
• under refrigeration at 2°C to 8°C (36°F to 46°F) for no more than 24
hours
Administration
infusion over 60 minutes through an IV line containing a sterile, non-
pyrogenic, low protein binding in-line filter (pore size of 0.2 micrometer
to 1.2 micrometer).

67. PEMBROLIZUMAB(KEYTRUDA)
INDICATIONS:
1.Unresectable or metastatic melanoma
2. Metastatic NSCLC
KEYTRUDA + carbo/pem: First-line treatment for mNSCLC
-Nonsquamous NSCLC
-Irrespective of PD-L1 expression
KEYTRUDA as monotherapy: First-line treatment for mNSCLC
-Nonsquamous or squamous NSCLC
-No EGFR or ALK genomic tumor aberrations
-High PD-L1 expression: TPS ≥50%
KEYTRUDA as monotherapy: Second-line or greater treatment for mNSCLC
-Nonsquamous or squamous NSCLC
-Previously treated with platinum-containing chemotherapy and EGFR or ALK therapy, if appropriate
-PD-L1 expression: TPS ≥1%
3. Recurrent or metastatic HNSCC
with disease progression on or after platinum-containing chemotherapy..

68. • DOSAGE AND ADMINISTRATION
Melanoma: 2 mg/kg every 3 weeks
NSCLC: 200 mg every 3 weeks.
HNSCC: 200 mg every 3 weeks.
intravenous infusion over 30 minutes.
DOSAGE FORMS AND STRENGTHS
For injection: 50 mg lyophilized powder in single-use vial for
reconstitution
Injection: 100 mg/4 mL (25 mg/mL) solution in a single-use vial

69. Adverse reactions ( ≥20%)
- fatigue, pruritus, diarrhea, decreased appetite, rash, dyspnea,
constipation, and nausea
• Immune-mediated adverse reactions including
pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe
skin reactions, and solid organ transplant rejection

70. Preparation and Administration
• Add 2.3 mL of Sterile Water by injecting the water along the walls of
the vial and not directly on the lyophilized powder (resulting
concentration 25 mg/mL).
• Slowly swirl the vial. Allow up to 5 minutes for the bubbles to clear.
Do not shake the vial.
• Withdraw the required volume from the vial(s) of KEYTRUDA and
transfer into an intravenous (IV) bag containing 0.9% Sodium Chloride
Injection, USP or 5% Dextrose Injection
• Mix diluted solution by gentle inversion. The final concentration of
the diluted solution should be between 1 mg/mL to 10 mg/mL.
Discard any unused portion left in the vial.

71. • Administer infusion solution
intravenously over 30 minutes
through an IV line containing a sterile, non-pyrogenic, low-protein
binding 0.2 micron to 5 micron in-line or add-on filter.
Do not co-administer other drugs through the same infusion line

72. • Store the reconstituted and diluted solution from the KEYTRUDA 50
mg vial either:
At room temperature for no more than 6 hours from the time of
reconstitution

73. • Resume KEYTRUDA in patients whose adverse reactions recover to Grade 0-1.
Permanently discontinue KEYTRUDA for any of the following:
• Any life-threatening adverse reaction (excluding endocrinopathies controlled with hormone replacement therapy)
• Grade 3 or 4 pneumonitis or recurrent pneumonitis of Grade 2 severity
• Grade 3 or 4 nephritis
• AST or ALT greater than 5 times ULN or
total bilirubin greater than 3 times ULN
For patients with liver metastasis who begin treatment with Grade 2 AST or ALT, if AST or ALT increases by greater than or equal to
50% relative to baseline and lasts for at least 1 week
• Grade 3 or 4 infusion-related reactions
• Inability to reduce corticosteroid dose to 10 mg or less of prednisone or equivalent per day within 12 weeks
• Persistent Grade 2 or 3 adverse reactions (excluding endocrinopathies controlled with hormone replacement therapy) that do not
recover to Grade 0-1 within 12 weeks after last dose of KEYTRUDA
• Any severe or Grade 3 treatment-related adverse reaction that recurs

75. THANK YOU