EPCORITAMAB-BYSP INJ,SOLN
Clinical Criteria Summary
Document 595
Indications
- Relapsed or Refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL)
Cytokine Release Syndrome (CRS) Management & Monitoring
- Time Course: Median time to CRS onset after most recent dose is 2 days; median duration is 5 days. Highest risk occurs minutes to hours after step-up or induction infusions, but may occur once patient is discharged.
- Grading & Management:
- Grade 1: Symptomatic/supportive care (acetaminophen 650mg PO Q6H PRN for fever ≥38.0°C; IV hydration). Hold therapy until CRS resolves, then resume (except Grade 4).
- Grade 2: Continue supportive care + IV bolus/supplemental O2 as needed. Tocilizumab 8mg/kg IV over 1 hour (max 800mg/dose), repeat q8h (limit 3 doses/24h, max 4 total). If hypotension refractory to fluids, add dexamethasone 10mg IV q8-12h.
- Grade 3: Admit to ICU. Continue supportive care + vasopressors if needed. Dexamethasone 10mg IV q6h for 3 days, then rapidly taper. Tocilizumab per Grade 2 if max dose not reached and no improvement on high-dose steroids.
- Grade 4: Admit to ICU. Discontinue BsAb. Continue supportive care + mechanical ventilation as needed. High-dose methylprednisolone (500mg q12h x3d, then taper). Tocilizumab per Grade 2 if indicated.
- General: Outpatient management for Grade >1 requires inpatient admission. Initial step-up therapy may require inpatient admission depending on the BsAb.
- Monitoring:
- Clinic/Outpatient: Daily vital signs and weights; daily CBC with differential and complete metabolic profile; coagulation parameters twice weekly; CRP and ferritin daily during step-up and first full dose, then PRN; assess and grade CRS at least daily or with status changes.
- Inpatient/ICU: Vital signs every 4 hours (while awake if stable); monitor oral/IV fluid I/O; daily weights; daily CBC/CMP; coagulation parameters twice weekly; CRP daily during step-up until CRS resolves; assess and grade CRS every 12 hours or with changes; cardiac/hemodynamic monitoring by telemetry.
ICANS/Neurotoxicity Management & Monitoring
- Presentation & Diagnosis: Typically manifests within 2-3 days of CRS onset. Symptoms range from subtle (loss of attentiveness, language dysfunction) to severe (delirium, dysphasia, lethargy, confusion, aphasia, depressed LOC, encephalopathy, seizures, tremor, ataxia, cerebral edema). Diagnosis is one of exclusion; rule out other causes (e.g., CNS-acting meds, infection via head CT/MRI or LP if indicated).
- Grading: Use ASTCT grading scale with ICE score (10-point encephalopathy assessment evaluating orientation, naming, following commands, writing, attention) and neurotoxicity domains (level of consciousness, seizure, motor findings, elevated ICP/cerebral edema).
- Management:
- Grade 1: Supportive care with IV hydration and aspiration precautions.
- Grade 2: Supportive care + dexamethasone 10mg IV x2 (or equivalent) q6-12h, reassess; repeat if no improvement; rapidly taper once symptoms improve to Grade 1.
- Grade 3/4: Transfer to ICU. High-dose methylprednisolone IV (1000mg q12h for 3 days, adjust frequency as needed) until Grade 1, then taper. Consider mechanical ventilation for airway protection. For concurrent CRS, add tocilizumab 8mg/kg IV over 1 hour, repeat q8h PRN (max 3 doses/24h).
- General: Hold, dose-reduce, or discontinue per prescribing information. Consider antiseizure prophylaxis for high-risk patients (prior seizure history, CNS disease, EEG findings, brain lesions). Multidisciplinary discussion and specialty consults (Neurology, Ophthalmology) as indicated.
- Monitoring: Physical exam and vital signs daily; neurologic exam every 8-12 hours or with status changes; grade neuro assessment with ICE score and ASTCT neurotoxicity domain; monitor for increased ICP (fundoscopy); monitor severe hyponatremia; reserve ICU for worsening condition, cerebral edema, status epilepticus, or Grade 3-4 ICANS.
Pre-medication & Supportive Care
- Pre-medication: Dexamethasone 16 mg IV (administered 60 minutes prior to BsAb).
- General supportive medications per FDA labeling include corticosteroids, antihistamines, and antipyretics. Antifungal prophylaxis should be considered in patients receiving corticosteroids.
Dosing & Administration
- Step-up dosing strategy is recommended to decrease CRS risk; package labels recommend step-up dosing in the inpatient setting due to long observation times for CRS/ICANS.
- Dose delays require review of prescribing information for restart recommendations.
Document 682
Exclusion Criteria
- Facility is not equipped to monitor and manage Cytokine Release Syndrome (CRS), if necessary
- Absolute Neutrophil Count < 1000/µL
- Platelet count < 75,000/µL (if no bone marrow involvement)
- Total bilirubin > 1.5 times the upper limit of normal (unless Gilbert’s syndrome or liver involvement)
- Alanine transaminase (ALT), aspartate transaminase (AST), and alkaline phosphatase > 3 times the upper limit of normal (unless liver involvement)
- Creatinine clearance < 45 ml/min
- Active or uncontrolled infection
- Unmanageable drug-drug interaction
- Pregnancy
- Lactating
Inclusion Criteria
- Relapsed or refractory, diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma
- Relapsed or refractory, follicular lymphoma (FL)
Additional Inclusion Criteria
- Previously treated with > 2 prior lines of therapy (including 1 line with anti-CD20 monoclonal antibody)
- Care is provided by a VA/VA Community Care oncology or hematology provider
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Goals of care and role of Palliative Care consult have been discussed and documented
Additional Inclusion Criteria (Select if applicable)
- For patients who can become pregnant and patients with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 4 months after stopping treatment
Monitoring & Administration Requirements
- Patients with diffuse large B-cell lymphoma (DLBCL) or high-grade B-cell lymphoma should be hospitalized for step-up dose on Cycle 1, Day 15 (first 48 mg dose) followed by 24 hours of monitoring
Document 683
Indications & Patient Population
- Relapsed or refractory diffuse large B-cell lymphoma (DLBCL), including DLBCL arising from indolent lymphoma and high-grade B-cell lymphoma (HGBCL)
- Relapsed or refractory follicular lymphoma (FL) grade 1-3A
Prior Therapy Requirements
- > 2 prior lines of therapy (LOT) for both DLBCL and FL indications
- For FL: must have received prior anti-CD20 monoclonal antibody, alkylator, or lenalidomide
Exclusion Criteria
- CNS lymphoma
- Allogeneic hematopoietic stem cell transplant (allo HSCT) or solid organ transplant (SOT) [DLBCL cohort]
- Active infection
- Impaired T-cell immunity [DLBCL cohort]
- HIV infection, cardiovascular disease (CV disease), autoimmune disease [FL cohort]
Dosing & Administration Requirements
- Requires step-up dosing regimen for both DLBCL and FL: Day 1 (0.16 mg SQ), Day 8 (0.8 mg SQ), Day 15 first full dose (48 mg SQ)
- Subsequent cycles follow a 28-day schedule with fixed 48 mg SQ dosing on specified days
- Therapy continues until progressive disease or toxicity
Safety Monitoring & Warnings
- Boxed warnings for Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
- Additional warnings include infections, cytopenias, and embryo-fetal toxicity
- First full dose must be administered in a hospital setting with monitoring for CRS/ICANS
VA Formulary & Clinical Pathway Notes
- Not included in VA Oncology Clinical Pathway for either DLBCL or FL indications
- Alternative options referenced to Appendix A (BiTE alternatives)