What is immunotherapy and when should it be considered as a treatment option for a patient with a medical condition such as cancer, autoimmune disorders, or allergies, under the guidance of a qualified healthcare professional?

Immunotherapy: Definition and Clinical Applications

Immunotherapy is a treatment modality that harnesses or modulates the immune system to fight disease, with established efficacy in allergic conditions (rhinitis, asthma, insect hypersensitivity) and cancer, while requiring careful patient selection based on specific disease characteristics and risk factors.

What Immunotherapy Is

Immunotherapy encompasses treatment approaches that stimulate, enhance, suppress, or desensitize the immune system to treat disease 1. The term applies broadly to:

• Allergen immunotherapy: Treatment to restore immune system ability to tolerate allergens, primarily used for allergic rhinitis, asthma, and insect hypersensitivity 1
• Cancer immunotherapy: Treatment using immune checkpoint inhibitors, adoptive cell therapy, or biologics to enhance anti-tumor immune responses 2, 3
• Immunomodulation: Therapeutic interventions aimed at modifying immune responses in autoimmune disorders 1

When to Consider Allergen Immunotherapy

Primary Indications

Allergen immunotherapy merits consideration as a treatment option for patients with allergic rhinitis (including ocular symptoms), allergic asthma, and stinging insect hypersensitivity 1. The evidence base includes:

• Multiple double-blind, placebo-controlled trials demonstrating efficacy for inhalant allergens including pollens, fungi, dust mites, and cockroaches 1
• Effectiveness demonstrated in both adults and children 1
• Significant improvements in symptom scores, medication use, and quality of life 1
• For dust mite allergy specifically, effect sizes range from 2.7-fold improvement in symptoms to 13.7-fold reduction in bronchial hyperreactivity 1

Patient Selection Criteria

Use standardized extracts when possible for preparing immunotherapy treatment sets 1. Selection requires:

• Documented IgE-mediated disease through skin testing or serum-specific IgE 1
• Correlation between allergen exposure and clinical symptoms 1
• Inadequate symptom control with pharmacotherapy and allergen avoidance alone 1

Special Populations Requiring Modified Approach

Children under 5 years: Can receive immunotherapy but may have difficulty cooperating with the program; benefits and risks must be carefully weighed 1.

Pregnant patients: Maintenance doses can be continued, but immunotherapy is usually not initiated during pregnancy due to risks of systemic reactions (spontaneous abortion, premature labor, fetal hypoxia) 1. Exception: Consider initiation for high-risk conditions like Hymenoptera anaphylaxis 1.

Elderly patients: Age alone should not preclude consideration, but evaluate for comorbidities (hypertension, coronary artery disease, cerebrovascular disease, arrhythmias) and medications that complicate anaphylaxis treatment (β-blockers) 1.

Patients with immunodeficiency or autoimmune disorders: Immunotherapy can be considered, as concern about increased risk is largely hypothetical with no substantive evidence of harm 1. For HIV-positive patients, consider immunotherapy only with CD4 count ≥400 cells/mL, no opportunistic infections, and no plasma HIV viremia 1.

When to Consider Cancer Immunotherapy

Established Indications

Cancer immunotherapy with checkpoint inhibitors (anti-PD-1, anti-PD-L1, anti-CTLA-4) is indicated for multiple malignancies including melanoma, non-small cell lung cancer, urothelial carcinoma, esophageal cancer, and microsatellite instability-high cancers 4.

Special Populations in Cancer Treatment

Solid organ transplant recipients: No absolute contraindication exists, but thorough discussion of benefits versus risks is essential 1. Renal transplant patients face particularly high allograft rejection rates (up to 78% in some series) occurring soon after immunotherapy initiation 1. Close monitoring of immunosuppressant drug levels and periodic dose adjustments are required 1.

Patients with autoimmune disorders: Not an absolute contraindication, but flare-ups of pre-existing disease occur in 27-50% of cases (10-25% high grade), with additional immune-related adverse events in 25-30% 1.

Pregnancy: Treatment with checkpoint inhibitors is not absolutely contraindicated but carries increased risk of pregnancy complications including abortion and premature delivery 1. Pregnancy during treatment must be avoided 1.

Allogeneic bone marrow transplant recipients: Previous anti-PD-1 treatment or subsequent transplantation carries high risk of graft-versus-host disease but may be considered when no other treatment options exist 1.

Conditions Where Immunotherapy Is NOT Recommended

Do not use allergen immunotherapy for:

• Food hypersensitivity 1
• Chronic urticaria or angioedema 1
• Low-dose immunotherapy, enzyme-potentiated immunotherapy, or provocation-neutralization-based immunotherapy 1

Limited or investigational evidence exists for:

• Atopic dermatitis (limited data suggest possible benefit when associated with aeroallergen sensitivity) 1
• Oral allergy syndrome (conflicting results) 1
• Sublingual/oral immunotherapy in the United States (no FDA-approved formulations as of 2011 guidelines) 1

Critical Safety Considerations

Life-threatening and fatal reactions can occur with allergen immunotherapy despite appropriate administration 1. Essential precautions include:

• Assessment of current health status before each injection 1
• Immediate availability of epinephrine and resuscitation equipment 1
• Observation period of at least 30 minutes post-injection 1
• Caution when transferring between physicians due to extract variability 1

For cancer immunotherapy, immune-related adverse events require prompt recognition and management with immunosuppression when indicated 4.