retifanlimab (Rx)

>10%

All grades

• Decreased hemoglobin (38%)
• Increased lipase (30%)
• Decreased lymphocytes (29%)
• Fatigue (28%)
• Decreased sodium (23%)
• Increased AST (23%)
• Musculoskeletal pain (22%)
• Increased ALT (21%)
• Increased alkaline phosphatase (20%)
• Increased amylase (19%)
• Pruritus (18%)
• Diarrhea (15%)
• Decreased neutrophils (13%)
• Decreased leukocytes (12%)
• Rash (11%)

1-10%

All grades

• Pyrexia (10%)
• Nausea (10%)
• Decreased potassium (9%)
• Increased calcium (8%)

Grades 3-4

• Decreased lymphocytes (10%)
• Increased lipase (3.4%)
• Decreased sodium (3.3%)
• Decreased neutrophils (3.3%)
• Increased ALT (3.3%)
• Musculoskeletal pain (2.9%)
• Increased AST (2.2%)
• Increased amylase (1.2%)
• Decreased hemoglobin (1.1%)
• Decreased leukocytes (1.1%)
• Increased alkaline phosphatase (1.1%)
• Decreased potassium (1.1%)
• Increased calcium (1.1%)
• Fatigue (1%)
• Rash (1%)

Contraindications

None

Cautions

Infusion-related reactions reported; interrupt or slow infusion rate, or permanently discontinue based on severity; consider premedication with antipyretic and/or an antihistamine in pateints with a history of previous systemic reactions to infusions of therapeutic proteins

Based on mechanism of action, can cause fetal harm when administered to pregnant females

Complications of allogeneic HSCT

• Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1–blocking antibody
• Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause)
• Closely monitor for evidence of transplant-related complications and intervene promptly; consider benefit versus risks of treatment with a PD-1/PD-L1–blocking antibody before or after an allogeneic HSCT

Severe and fatal immune-mediated adverse reactions

• Also see Dosage Modifications
• Can occur in any organ system or tissue and at any time after starting treatment with a PD-1/PD-L1–blocking antibody
• While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1–blocking antibodies, these adverse reactions can also manifest after discontinuation of PD-1/PD-L1–blocking antibodies
• May affect more than 1 body system simultaneously

• Immune-mediated toxicities reported include

  • Pneumonitis; in patients treated with other PD-1/PD-L1–blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation
  • Colitis; in cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies
  • Hepatitis
  • Endocrinopathies (eg, adrenal insufficiency, hypophysitis, thyroiditis, hyperthyroidism, hypothyroidism, type 1 diabetes mellitus, hypoparathyroidism)
  • Nephritis with renal dysfunction
  • Dermatologic
  • Cardiac, vascular
  • Gastrointestinal
  • Musculoskeletal
  • Neurological
  • Ocular
  • Hematologic

Pregnancy

Based on mechanism of action, can cause fetal harm when administered to pregnant females

Verify pregnancy status in females of reproductive potential before initiating

Inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death

Human IgG4 immunoglobulins (IgG4) are known to cross the placenta; therefore, retifanlimab has potential to be transmitted from mother to the developing fetus; advise patient of potential risk to fetus

Contraception

• Advise females of reproductive potential to use effective contraception during treatment and for 4 months after last dose

Lactation

Data are not available regarding presence of retifanlimab in human milk, or its effects on breastfed children or on milk production

Maternal IgG is known to be present in human milk; effects of local gastrointestinal exposure and limited systemic exposure in breastfed children are unknown

Because of potential for serious adverse reactions in breastfed children, do not breastfeed during treatment and for 4 months after last dose

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Monoclonal antibody that targets checkpoint inhibitor PD-1 (programmed death 1) and blocks its interaction with the PD-1 ligands PD-L1 and PD-L2, releasing the PD-1 pathway-mediated inhibition of the immune response, including antitumor immune response, thereby decreasing tumor growth

Binding of PD-L1 and PD-L2 to the PD-1 receptor found on T cells inhibits T-cell proliferation and cytokine production

Absorption

Steady-state achieved at ~6 months

Distribution

Vd: 6 L

Elimination

Half-life: 19 days

Clearance: 0.31 L/day (first dose); decreased over time to 0.24 L/day

IV Incompatibilities

Do not coadminister other drugs through same infusion line

IV Compatibilities

0.9%NaCl

D5W

IV Preparation

Visually inspect vial for particulate matter and discoloration before use

Solution should appear clear to slightly opalescent, colorless to pale yellow, and free of particles

Discard if solution is cloudy, discolored, or contains particulate matter

Do not shake vial

Dilute solution

• Withdraw 20 mL (500 mg) from 1 vial and discard any unused portion
• Dilute with either 0.9% NaCl or D5W to final concentration between 1.4-10 mg/mL
• Use polyvinylchloride (PVC) and di-2-ethylhexyl phthalate (DEHP), polyolefin copolymer, polyolefin with polyamide, or ethylene vinyl acetate infusion bags
• Do not shake; mix diluted solution by gentle inversion
• Visually inspect infusion bag for particulate matter and discoloration before administration; discard if solution is discolored or contains particulate matter

IV Administration

Do not administer using a polyurethane infusion set

Infuse IV over 30 minutes through a polyethylene or PVC with DEHP IV line containing a sterile, non-pyrogenic, low-protein binding polyethersulfone, polyvinylidene fluoride, or cellulose acetate 0.2 to 5 micron in-line or add-on filter or 15 micron mesh inline or add-on filter

Do NOT administer as IV push or bolus injection

Storage

Unopened vial

• Refrigerate at 2-8ºC (36-46ºF) in original carton to protect from light
• Do not freeze or shake

Diluted solution

• May store at room temperature up to 25ºC (77ºF) for no more than 8 hr from time of preparation to end of infusion, OR
• Refrigerate at 2-8ºC (36-46ºF) for no more than 24 hr from time of preparation to end of infusion
• If refrigerated, allow diluted solution to come to room temperature before administration
• Administer within 4 hr (including infusion time) once removed from refrigerator
• Do not freeze or shake solution
• Protect from light