Pocket Oncology (Pocket Notebook Series), 1st Ed.

MONOCLONAL ANTIBODIES

Kristen Beyer

Source Infixes Used for Naming Monoclonal Antibodies

Alemtuzumab (Campath)

Mechanism of action: Binds to CD52 resulting in Ab-dependent lysis of malignant cells

Dosing/dose adjustments: Given IV or SQ, ↑ from 3–10 mg IV daily or 3 mg to 10 mg SQ 3×/wk, if tolerated, may ↑ to 30 mg IV/SQ 3× weekly, no renal or hepatic adjustments recommended

PK/PD: Clearance ↓ w/repeated dosing (due to ↓ of CD52 receptors), T1/2 ∼11 h after 1st 30 mg dose

Adverse effects: Pancytopenia (DLT, time to nadir ~30 d), GI upset, pneumonitis, HoTN, HTN, HSR

DDI: Live virus vaccines (vaccinial infxn may develop)

Clinical pearls: Premedicate for HSR w/APAP & diphenhydramine before every dose, ppx for PCP & HSV, risk of CMV infxn during & at least 2 mos after last dose

Bevacizumab (Avastin)

Mechanism of action: Binds to VEGF resulting in ↓ proliferation of endothelial cells & ↓ angiogenesis

Dosing/dose adjustments: 5 –15 mg/kg IV every 14–21 d, no renal or hepatic adjustments recommended, temporarily hold for proteinuria

PK/PD: T1/2 ∼20 d

Adverse effects: HTN, thrombosis, GIB, thrombocytopenia, proteinuria

DDI: No known significant interactions

Clinical pearls: Pts w/SBP >150 mmHg or DBP >100 mmHg, recent hemoptysis, surgery/bx, or new onset of thrombosis require further evaluation before initiating tx

Brentuximab Vedotin (Adcetris)

Mechanism of action: Binds CD30 causing cell cycle arrest & apoptosis

Dosing/dose adjustments: 1.8 mg/kg every 3 wks, no renal or hepatic dose adjustments recommended. Adjust dose for tox (neutropenia, HSR, peripheral neuropathy, PML, Stevens-Johnson)

PK/PD: Hepatically metabolized via CYP3A4/5, fecal excretion, T1/2 ∼5 d

Adverse effects: Peripheral neuropathy (DLT), pancytopenia, URI

DDI: CYP3A4 inhibitors/inducers (↑/↓ conc. of brentuximab)

Cetuximab (Erbitux)

Mechanism of action: EGFR inhibiting cell growth & ↑ apoptosis

Dosing/dose adjustments: 400 mg/m2 IV loading dose, 250 mg/m2 IV weekly, no renal or hepatic dose adjustments recommended

PK/PD: T1/2 ∼112 h

Adverse effects: Acneiform rash (w/in first 2 wks), pruritus, ↓ Mg, GI upset, anemia, HSR

DDI: No known significant interactions

Clinical pearls: No therapeutic benefit in pts w/mutated Kras

Ibritumomab (Zevalin)

Mechanism of action: CD20-directed radioimmunoconjugate (bound to Yttrium-90) binding results in apoptosis

Dosing/dose adjustments: Step (1) rituximab IV; step (2) rituximab IV then ibritumomab IV, dose (0.3–0.4 mCi/kg) dependent on plt count (do not administer if plts <100000 K/mcL), no renal or hepatic dose adjustments recommended

PK/PD: Distributes to all lymphoid cells, Yttrium-90 T1/2 ∼64 h

Adverse effects: Prolonged pancytopenia (B-cell recovery starts in ∼12 wks)

DDI: Anticoagulants (↑ risk of bleeding)

Ofatumumab (Arzerra)

Mechanism of action: Binds CD20 causing B-cell lysis

Dosing/dose adjustments: 300 mg IV × 1, then 2000 mg IV weekly × 7 doses, then 2000 mg every 4 wks × 4 doses, no renal or hepatic adjustments recommended

PK/PD: T1/2 doses 4–12 ∼14 d

Adverse effects: Neutropenia (may be >2 wks), URI

DDI: Live vaccines (vaccinial infxn may develop)

Clinical pearls: Premedicate for HSR w/APAP, antihistamine & corticosteroid for doses 1, 2, & 9

Panitumumab (Vectibix)

Mechanism of action: Binds EGFR inhibiting cell growth & ↑ apoptosis

Dosing/dose adjustments: 6 mg/kg IV every 14 d, no renal or hepatic dose adjustments recommended. Adjust dose for tox (HSR, dermatologic).

PK/PD: T1/2 ∼7.5 d

Adverse effects: Acneiform rash, ↓ Mg, ↓ Ca, eyelash growth, HSR

DDI: No known significant interactions

Clinical pearls: No therapeutic benefit in pts w/mutated Kras

Pertuzumab (Perjeta)

Mechanism of action: Binds to HER-2 inhibiting cell growth & ↑ apoptosis (binds to a different HER2 epitope than trastuzumab)

Dosing/dose adjustments: 840 mg IV × 1, then 420 mg every 3 wks, no renal or hepatic dose adjustments recommended

PK/PD: T1/2 18 d

Adverse effects: Cardiotoxicity, HSR, diarrhea, leukopenia, neutropenia

DDI: No known significant interactions

Rituximab (Rituxan)

Mechanism of action: Binds CD20 causing B-cell lysis

Dosing/dose adjustments: 375 mg/m2 IV, frequency dependent on regimen, no renal or hepatic dose adjustments recommended

PK/PD: Detectable in serum for 3–6 mos after completion

Adverse effects: Lymphopenia (B-cell recovery begins ∼6 mos after completion), viral reactivation

DDI: Live vaccines (vaccinial infxn may develop)

Clinical pearls: Split dose over 2 d for abs lymph ≥20000 K/mcL or high tumor burden, screen for hepatitis B infxn prior to tx

Tositumomab (Bexxar)

Mechanism of action: CD20-directed radioimmunoconjugate (bound to Iodine-131) binding results in apoptosis

Dosing/dose adjustments: (1) Dosimetric step, (2) therapeutic step, dose depends on plts (do not administer if plts <100000 K/mcL), no renal or hepatic dose adjustments recommended

PK/PD: At 5 d, total body clearance of Iodine-131 is 67% of a dose

Adverse effects: Prolonged pancytopenia (wks-mos, B-cell recovery at ∼12 wks), hypothyroidism, GI upset

DDI: Anticoagulants (↑ risk of bleeding)

Clinical pearls: Give thyroid protective agent (1 d before & 2 wks after tx completed)

Trastuzumab (Herceptin)

Mechanism of action: Binds to HER-2 resulting in cellular cytotoxicity

Dosing/dose adjustments: Loading dose 4–8 mg/kg IV, followed by 2–6 mg/kg maintenance dose IV weekly or every 3 wks, no renal or hepatic dose adjustments recommended

PK/PD: T1/2 ∼6–16 d

Adverse effects: CMP (DLT), GI upset, rash, fever, pain

DDI: Anthracyclines (potential ↑ in cardiac tox)

Information based on publicly available drug inserts from Genzyme, Genentech, Seattle Genetics, Eli Lilly, Teva, GlaxoSmithKline, and Amgen