Pediatric Virtual Symposium 2025 Study Notes

Pediatric Virtual Symposium 2025

  • Date: Live on October 10, 2025
  • Access: Participants can access sessions through December 31, 2025
  • Topic: Advances in Immunotherapy for the Treatment of Childhood Cancer
  • Speaker: Jessica D. Murphy, DNP, CPNP-AC, CPHON, CNE
    • Assistant Professor at the Johns Hopkins School of Nursing
    • Pediatric Oncology/BMT Nurse Practitioner at the Johns Hopkins Children's Center
    • Disclosure: No conflicts to disclose

Objectives of the Session

Learners will be able to:

  1. Summarize recent advancements in immunotherapeutic agents for the treatment of childhood cancers.
  2. Describe the administration and monitoring requirements for various immunotherapeutic agents.

Cancer Treatments Timeline

Early 1900s

  • Limited understanding of cancer.
  • Surgery remained the sole treatment option.

1920s

  • Radiation Therapy introduced, but limited use in children.

1940s

  • Chemotherapy introduced with nitrogen mustard.
  • 1947: Dr. Sidney Farber established the Children's Cancer Research Foundation.

1950s

  • Development of combination (multi-drug) chemotherapy.

1960s

  • Formation of clinical trial groups.

1970s

  • Improvements in survival rates due to multi-drug regimens and enhanced surgical methods.

1980s

  • Increased focus on reducing side effects and improving survivorship.

1990s

  • Introduction of targeted therapies.

2000s

  • Advances in genomics and mutation identification; personalized therapies emerged.
  • Evolution of immunotherapy usage.

2010s

  • Expanding application of immunotherapy, including FDA approval of CAR-T in 2018.

2020s

  • Continued advancements in genetic targeting and immunotherapy leading to better survival rates and long-term outcomes.

Survival Rates

  • Detailed survival rate statistics were indicated but not specified in this segment of the transcript.

What is Immunotherapy?

  • Definition: A form of treatment that utilizes a patient’s own immune system to combat diseases.
  • Mechanism:
    • Boosts or alters the immune system functioning to eliminate cancer cells.

Pros and Cons of Immunotherapy

Pros

  • Targeted Action: Directly targets cancer cells while sparing normal cells.
  • Fewer Long-Term Side Effects: Potentially reduces long-term adverse effects compared to traditional chemotherapy.
  • Improved Survival Rates: Associated with better outcomes for certain cancers.
  • Sustained Response: Can lead to prolonged remission or response.

Cons

  • Infusion Reactions: Common reactions may occur during treatment.
  • Increased Risk of Toxicity: Higher risk for some patients.
  • Impact on Immune Function: Can compromise the ability to fight off infections.
  • Pseudoprogression: A phenomenon where tumors may appear to grow before they actually shrink, complicating treatment assessments.
  • Cost: Often a significant financial burden for patients.

Comparison: Immunotherapy vs. Chemotherapy

Types of Immunotherapy

  1. Monoclonal Antibodies

    • Definition: Lab-created versions of immune system proteins that can bind to specific antigens on cancer cells.
    • Examples: Blinatumomab, Dinutuximab.

  2. Checkpoint Inhibitors

    • Mechanism: Blocks specific pathways in the immune system to enhance immune response against cancer cells.
    • Examples: Nivolumab, Pembrolizumab.

  3. Vaccines

    • Function: Activate the immune system to recognize and attack tumor-associated antigens.
    • Note: Currently, no FDA approvals for treatment of childhood cancers.

  4. Cytokines

    • Definition: Signaling proteins that modulate the immune response and hematopoiesis.
    • Functions: Inhibit growth, induce cell death, cease angiogenesis, increase differentiation, enhance tumor antigen presentation.
    • Examples: Sargramostim (GM-CSF), Aldesleukin (IL-2).

  5. Chimeric Antigen Receptor (CAR) T-cell Therapy

    • Mechanism: T-cells are genetically modified to express a receptor that targets specific cancer cells, then reinfused into the patient.
    • Examples: Kymriah, Yescarta.

Specific Treatments

Dinutuximab (Unituxin)

  • Type: Monoclonal antibody used for metastatic neuroblastoma.
  • Mechanism: Binds to GD2 on the cell surface; induces antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).
  • Administration: Used in conjunction with GM-CSF (cytokine).
  • Cycle: Infusion over 10-20 hours for 4 days.
  • Supportive Care Requirements: PCA, antihistamines, acetaminophen, gabapentin, antiemetics; close monitoring with strict I/O, regular vital checks, and daily or BID weights.
  • Side Effects: Pain, fever, capillary leak syndrome, hypotension, and anaphylaxis.

Blinatumomab (Blincyto)

  • Type: Monoclonal therapy (BiTE) used for acute lymphoblastic leukemia (ALL).
  • Mechanism: Binds to CD3 on T-cells and links to CD19 on cancer cells leading to ADCC.
  • Hospitalization: Initial hospitalization required for close monitoring and supportive care due to cytokine release syndrome (CRS) and neurotoxicity risk.
  • Outpatient Infusion: After stabilization, outpatient 28-day infusion.
  • Side Effects: Generally mild; may include headache, decreased level of consciousness (LOC), CRS, and hypogammaglobulinemia.

Nivolumab (Opdivo)

  • Type: Checkpoint inhibitor targeting PD-1.
  • Approval: FDA approved for individuals 12 years and older with colorectal cancer, melanoma, and undergoing research on solid tumors.
  • Administration: Outpatient infusion over 30 minutes, can be used alone or in combination with other medications.
  • Common Side Effects: Fatigue, rash, pain, gastrointestinal symptoms, cough, shortness of breath, pneumonitis, immune-related adverse events (IrAEs).

Tisagenlecleucel (Kymriah)

  • Type: CAR T-cell therapy for B-cell ALL in patients under 25 years old and adults with B-cell lymphoma.
  • Mechanism: Genetically engineered receptor recognizes CD19 on cancer cells; activates and kills the cells.
  • Hospitalization: Required post-infusion and includes lymphodepleting chemotherapy.
  • Side Effects: Includes cytokine storm, neurotoxicity, B-cell aplasia, cytopenias, and hypogammaglobulinemia.

Side Effects & Monitoring

Immune-Related Adverse Events (IrAEs)

  • Common symptoms:
    • Skin Reactions: Rash, pruritus (itching), vitiligo, dermatitis.
    • Gastrointestinal Toxicity: Diarrhea, colitis, abdominal pain, nausea indicating inflammation of the gastrointestinal tract.
    • Endocrine Disorders: Hyperthyroidism, hypothyroidism, adrenal insufficiency affecting hormone-producing glands.
    • Pneumonitis: Symptoms include cough, dyspnea, and chest pain indicating lung tissue inflammation.
    • Hepatitis: Elevated liver enzymes, jaundice, fatigue indicating liver inflammation.
    • Nephritis: Elevated creatinine levels, decreased urine output associated with kidney inflammation.
    • Myocarditis: Symptoms include chest pain and arrhythmias; indicates inflammation of the heart muscle.
    • Neurologic Toxicity: Symptoms such as encephalitis, seizures, neuropathy, myasthenia gravis; damage to the nervous system may occur.
    • Generalized Immune Activation: Persistent fever.

Cytokine Release Syndrome (CRS)

  • Definition: Overwhelming activation of immune cells leading to heightened inflammatory cytokine release.
  • Consequences: Systemic response with potential for organ damage and death.
  • Management: Early recognition is critical, treatment can include tocilizumab and steroids.

Immune Effector Cell Associated Neurotoxicity (ICANS)

  • Association with CAR T-cell therapy impacts 7-72% of patients, often preceded by CRS.
  • Symptoms include decreased LOC, confusion, headache, potential for seizures, encephalopathy, or coma.
  • Management: Treatment in PICU with steroids and supportive care.

Future Advancements

References

  • A comprehensive list of references supporting the research and findings presented, including various articles and reviews pertinent to immunotherapy and its effects in pediatric oncology.
  • Critical studies and consensus opinions from various renowned healthcare bodies were included to support evidence-based practices in pediatric health care.