ELRANATAMAB-BCMM 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 619
Exclusion Criteria
- Known hypersensitivity to elranatamab or its excipients (e.g., polysorbate 80)
- Active viral, bacterial, or uncontrolled systemic fungal infection
- Known active central nervous system disease or signs of meningeal involvement
- Pregnancy
- Lactating
Inclusion Criteria
- Relapsed or refractory multiple myeloma in a patient who has received at least four prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody
- Oncologic care provided by a VA or VA Community Care oncology provider certified with the ELREXFIO REMS Program
- Goals of care and role of Palliative Care consult discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- Hospitalization required due to risk of Cytokine Release Syndrome: 48 hours after step-up dose #1 and 24 hours after step-up dose #2
Additional Inclusion Criteria
- For patients who can become pregnant or have partners who can become pregnant: counseling provided on potential risks vs. benefits of treatment and use of effective contraception during therapy and for four months after stopping treatment
Document 620
Indication & Patient Population
- Adults with relapsed or refractory multiple myeloma
- Accelerated approval contingent upon clinical benefit verified in a confirmatory trial
Prior Therapy & Refractoriness Requirements
- Received at least four prior lines of therapy (LOT)
- Prior regimens must include a proteasome inhibitor, an immunomodulatory agent (IMiD), and an anti-CD38 monoclonal antibody
- Refractory to at least one proteasome inhibitor, at least one IMiD, and at least one anti-CD38 monoclonal antibody
- May be used in patients with prior BCMA-directed therapy exposure (noted to have lower ORR in this population)
Dosing & Administration
- Injectable for subcutaneous administration
- Step-up dosing: Day 1: 12 mg SQ; Day 4: 32 mg SQ; Day 8: 76 mg SQ (first full dose)
- Administer weekly through week 24 following step-up
- After 6 cycles, if partial response or better at 6 months and maintained for > 2 months, switch to dosing every 2 weeks until disease progression or unacceptable toxicity
Monitoring & Safety Requirements
- Hospitalization recommended for the first two doses (step-up phase)
- REMS program required
- Monitor for cytokine release syndrome (CRS) and neurotoxicity including ICANS
- Manage risks of infections, neutropenia, hepatotoxicity, and embryo-fetal toxicity
Formulary & Place in Therapy
- NCCN: Preferred bispecific antibody after > 4 LOT (category 2A)
- VA Multiple Myeloma pathway: Listed as preferred for RRMM s/p > 4 LOT
- Provides an option for patients with limited access to CAR T-cell therapy due to specialized centers or manufacturing issues