Case Presentation

Patient Profile

  • 67-year-old female with recently diagnosed chronic lymphocytic leukemia (CLL).
  • Past medical history: hypertension, type 2 diabetes (well controlled), and mild chronic kidney disease (eGFR ~55 mL/min).
  • No known drug allergies.

Treatment Setting

  • Presenting for Cycle 1, Day 1 of obinutuzumab (Gazyva®) as part of first-line therapy.
  • Standard premedications were administered 30 minutes prior to infusion: acetaminophen 650 mg PO, diphenhydramine 25 mg IV, and dexamethasone 20 mg IV.
  • Baseline vitals: T 36.9 °C, HR 82, BP 134/76, RR 16, SpO₂ 98% RA.

Infusion Course

  • Gazyva infusion started at the recommended initial rate of 25 mg/hr.
  • Within 20 minutes, the patient reported:
    • Sudden onset chills and diffuse shaking rigors
    • Throbbing frontal headache rated 7/10
    • Associated nausea without emesis
    • Profuse diaphoresis noted by nursing staff
  • Vitals at this point: T 38.5 °C, HR 104, BP 128/70, RR 18, SpO₂ 96% RA.

Initial Management

  • Infusion stopped immediately.
  • Oxygen via nasal cannula at 2 L/min started for comfort.
  • IV fluids (normal saline at 75 mL/hr) initiated.
  • Patient continued to experience persistent chills, headache, and rigors despite the pause.

Medications Administered

  • Acetaminophen 1,000 mg IV given for fever and headache.
  • Diphenhydramine 50 mg IV push administered as additional H1 blockade.
  • Hydrocortisone 100 mg IV administered given ongoing systemic symptoms.
  • Because the patient remained uncomfortable with violent rigors, meperidine 25 mg IV was given, resulting in gradual resolution of shaking within 15 minutes.

Outcome

  • Symptoms improved significantly: T 37.7 °C, HR 88, BP 130/72, SpO₂ 98% RA.
  • After multidisciplinary discussion, the infusion was resumed at 50% of the prior rate (12.5 mg/hr) and subsequently escalated per protocol without recurrence.
  • Patient observed closely for the remainder of the infusion and for 1 hour post-infusion; discharged home in stable condition.

Context: Gazyva (obinutuzumab) infusion reactions

  • Gazyva (anti-CD20 mAb) is well known for infusion-related reactions (IRRs), especially during the first infusion.
  • Typical manifestations include chills, rigors, headache, fever, nausea, hypotension, rash, or bronchospasm.
  • Mechanism: thought to be cytokine release and complement activation, not just histamine release.

Teaching Points

  1. Infusion-related reactions with Gazyva are most common during the first cycle, driven by cytokine and complement activation.
  2. Symptoms such as chills, rigors, and headache can occur despite standard premedication and may require additional intervention.
  3. Meperidine is appropriate for severe or persistent rigors that do not improve with antipyretics or antihistamines.
  4. Always stop the infusion, stabilize the patient, and restart at a slower rate once symptoms have resolved.
  5. Escalate to epinephrine if airway compromise, hypotension, or severe systemic signs occur.