TECLISTAMAB-CQYV INJ,SOLN
Clinical Criteria Summary
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Exclusion Criteria
- Known hypersensitivity to teclistamab or its excipients
- Known active central nervous system involvement or signs of meningeal involvement
- Active viral, bacterial, or uncontrolled systemic fungal infection
- Pregnancy
- Breastfeeding
Inclusion Criteria
- Relapsed or refractory multiple myeloma in a patient who has received at least four prior lines of therapy including a proteasome inhibitor, and immunomodulatory agent, and an anti-CD38 monoclonal antibody
- Care for the oncologic condition provided by VA or VA Community Care oncology provider certified with the Tecvayli REMS program
- Goals of care and role of Palliative Care consult have been discussed and documented
- Eastern Cooperative Oncology Group (ECOG) Performance Status 0 to 2
- All step-up doses and first treatment dose must be administered in a hospital setting with observation for 48 hours following each dose due to the risk of cytokine release syndrome (CRS) and neurologic toxicity, including immune effector cell-associated neurotoxicity (ICANS)
- Tocilizumab may be useful in patients not responding to dexamethasone for the management of CRS
Additional Inclusion Criteria
- 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 five months after stopping treatment
- For patients who are breastfeeding: Counseling provided on avoiding breastfeeding while on treatment and for five months after stopping treatment
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Indication & Patient Population
- Relapsed or refractory multiple myeloma in patients who have received at least four prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody.
Dosing & Administration
- Subcutaneous administration only.
- Step-up dosing schedule: Day 1 (0.06 mg/kg), Day 4 (0.3 mg/kg), Day 7 (1.5 mg/kg). Doses may be administered 2 to 4 days after the prior dose, up to 7 days to allow for resolution of adverse reactions.
- Weekly dosing schedule: 1.5 mg/kg once weekly starting one week after the first treatment dose and doses thereafter.
- Pre-treatment medications required 1 to 3 hours prior to each step-up dose and the first treatment dose: corticosteroid (oral or IV dexamethasone 16 mg), H1 receptor antagonist (oral or IV diphenhydramine 50 mg or equivalent), and antipyretic (oral or IV acetaminophen 650-1000 mg or equivalent). Pre-treatment may also be required for subsequent doses in patients who repeat the step-up schedule due to delay or experience CRS.
Hospitalization & Monitoring Requirements
- Patients must be hospitalized for 48 hours following administration of each step-up dose due to the risk of cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS).
- Monitor liver enzymes and bilirubin at baseline and during treatment due to hepatotoxicity risk.
- Monitor for signs and symptoms of infection; withhold treatment in patients with an active infection during the step-up dosing period.
- Monitor blood cell counts at baseline and during treatment; consider granulocyte colony stimulating factors (GCSF) for grade 4 neutropenia or grade 3 neutropenia accompanied by an infection.
Toxicity Management Criteria
- CRS: Withhold teclistamab until CRS resolves. Administer pretreatment medications prior to next dose. Hospitalize patient for 48 hours following the next dose for Grade 2+ CRS. Permanently discontinue for Grade 3-4 CRS.
- ICANS: Withhold teclistamab until ICANS resolves. Administer dexamethasone 10 mg IV every 6 hours until resolution to grade 1 or less, then taper. Monitor neurologic symptoms and consider neurologist consultation. Hospitalize patient for 48 hours following the next dose for Grade 2+ ICANS. Permanently discontinue for Grade 3-4 ICANS.
REMS & Facility Requirements
- Available only through the TECVAYLI REMS program.
- Prescribers must be certified and complete training; patients must be counseled on risks and provided a patient wallet card.
- Healthcare settings that dispense teclistamab must be certified with the program and verify ordering providers are certified.
- Treatment restricted to facilities capable of admitting patients for 48 hours to receive all step-up doses and first treatment dose, with staff trained in managing CRS and ICANS.
Special Populations & Contraindications
- Contraindications: None explicitly stated.
- Embryo-fetal toxicity: Advise females of reproductive potential to use effective contraception during treatment and for five months after the last dose. Advise parents not to breastfeed during and for five months after the last dose.
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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.