Monoclonal Antibodies in Cancer

Monoclonal antibodies bind specific tumour or immune targets and act by blocking signalling, recruiting immune effector cells, activating complement, delivering a toxin, or releasing a restraint on T cells. They are large proteins given intravenously or subcutaneously; names end in -mab, with prefixes marking origin (chimeric, humanised, fully human).

Classification. By target and mechanism:

• Anti-CD20 (rituximab, obinutuzumab, ofatumumab): lymphoma, chronic lymphocytic leukaemia.
• Anti-HER2 (trastuzumab, pertuzumab).
• Anti-EGFR (cetuximab, panitumumab).
• Anti-VEGF (bevacizumab, ramucirumab).
• Anti-CD38 (daratumumab, isatuximab): myeloma.
• Immune checkpoint antibodies (anti-PD-1, anti-PD-L1, anti-CTLA-4).
• Antibody drug conjugates and bispecific T-cell engagers.

Pharmacokinetics. Half life of 2 to 4 weeks, cleared by proteolysis with no hepatic or renal dose adjustment; target-mediated clearance means higher doses are needed with high tumour burden.

• Rituximab 375 mg/m2 weekly for 4 doses, or 375 mg/m2 with each chemotherapy cycle; 500 mg/m2 in chronic lymphocytic leukaemia; subcutaneous forms exist.
• Trastuzumab 8 mg/kg loading dose then 6 mg/kg every 3 weeks (adjuvant for 1 year).
• Bevacizumab 5 to 15 mg/kg every 2 to 3 weeks.
• Cetuximab 400 mg/m2 loading dose then 250 mg/m2 weekly (RAS wild-type colorectal cancer; head and neck).
• Panitumumab 6 mg/kg every 2 weeks.
• Daratumumab 16 mg/kg weekly for 8 weeks, every 2 weeks for 16 weeks, then monthly.

Differences. Anti-CD20 antibodies deplete B cells (infection, hepatitis B reactivation); anti-HER2 antibodies cause cardiotoxicity; anti-EGFR antibodies cause rash and low magnesium; anti-VEGF antibodies cause hypertension, proteinuria and poor wound healing.

• Lymphoma: rituximab added to chemotherapy improves survival in B-cell lymphoma and chronic lymphocytic leukaemia.
• HER2-positive breast and gastric cancer: trastuzumab, with confirmed HER2 status.
• Colorectal cancer: cetuximab or panitumumab only when the tumour is RAS wild-type; bevacizumab with chemotherapy.
• Myeloma: daratumumab with an immunomodulatory drug and dexamethasone.
• Infusion reactions: premedicate with paracetamol 1 g, chlorphenamine 10 mg, and hydrocortisone 100 mg; start the first infusion slowly (rituximab 50 mg/hour, increasing by 50 mg/hour every 30 minutes to a maximum of 400 mg/hour); stop for severe reactions.
• Before treatment: hepatitis B surface antigen and core antibody, HIV, tuberculosis assessment, cardiac function for anti-HER2 drugs, and blood pressure and urine protein for bevacizumab.
• Biosimilars: biosimilar rituximab, trastuzumab and bevacizumab reduce cost and widen access in East Africa where supplied.

Selection. Match the antibody to a biomarker; confirm funding for a full course before starting.

Contraindications. Hypersensitivity; active serious infection; hepatitis B reactivation risk without prophylaxis (anti-CD20); left ventricular ejection fraction under 50 percent (trastuzumab, caution); pregnancy (trastuzumab: oligohydramnios, foetal harm).

Adverse effects. Infusion reactions and cytokine release, infections, hepatitis B reactivation, progressive multifocal leukoencephalopathy (anti-CD20), cardiomyopathy (trastuzumab), hypertension, proteinuria, bleeding, thromboembolism and gastrointestinal perforation (bevacizumab), acneiform rash and hypomagnesaemia (cetuximab, panitumumab), and neutropenia.

Interactions. Trastuzumab with anthracyclines increases cardiac failure risk; antihypertensives may need to be held before rituximab infusion; live vaccines are contraindicated.

Special groups.

• Pregnancy: avoid; antibodies cross the placenta in the second and third trimesters.
• Breastfeeding: avoid during treatment and for months after.
• Children: rituximab and dinutuximab are used in specialist regimens.
• Older adults: monitor for infection and cardiac effects.
• Kidney and liver impairment: no adjustment.

Monitoring. Vital signs during infusion, full blood count, immunoglobulins with prolonged anti-CD20 treatment, hepatitis B markers, blood pressure and urine protein (bevacizumab), left ventricular ejection fraction every 3 months (trastuzumab), and magnesium (anti-EGFR).

Referral and escalation. Anaphylaxis, cytokine release syndrome, ejection fraction fall, bowel perforation, or new neurological symptoms (progressive multifocal leukoencephalopathy) need urgent specialist care.