ELRA; ELRA(RAMP)

a. Maintain a minimum of 2 days between step-up dose 1 (12 mg) and step-up dose 2 (32 mg).
b. Maintain a minimum of 3 days between step-up dose 2 (32 mg) and the first full treatment (76 mg) dose.
c. Maintain a minimum of 6 days between treatment doses.

Inpatient admission may be required for cytokine release syndrome monitoring.

Note: ST-QBP funding for ambulatory administration only

REPEAT EVERY 28 DAYS

Until disease progression or unacceptable toxicity

Use regimen code ELRA(RAMP) for cycle 1, then ELRA for subsequent cycles.

• Also refer to CCO Antiemetic Summary.
   

Screen for hepatitis B virus in all cancer patients starting systemic treatment. Refer to the hepatitis B virus screening and management guideline.

Pre-medication (prophylaxis for cytokine release syndrome)

Administer 1 hour before the first 3 elranatamab doses* (step-up doses & first treatment dose):

• Acetaminophen 650 mg PO (or equivalent)
• Dexamethasone 20 mg PO or IV (or equivalent)
• Diphenhydramine 25 mg PO (or equivalent)**

^{*Assess the need for premedications in subsequent doses (see Table 3).}

^{** Central nervous system (CNS) effects of diphenhydramine may make it challenging to identify ICANS. Consider cetirizine, which has a lower incidence of CNS effects.}

Other Supportive Care:

• Consider prophylaxis against Pneumocystis jirovecii pneumonia (PJP) and herpes virus infections.
• Consider other antimicrobial prophylaxis as per local guidelines.
• Elranatamab should be administered to adequately hydrated patients.

Doses should be modified according to the protocol by which the patient is being treated.

Do not start treatment with elranatamab in patients with active infection.

Dose reductions are not recommended.

Doses may be delayed due to toxicity. Recommendations on restarting after a dose delay are listed in Table 3.

Refer to the T-Cell Engaging Antibodies guideline for a detailed description of CRS, ICANS and their management.

Table 1 -  CRS and ICANS Toxicity

^a Grade based on American Society for Transplantation and Cellular Therapy (ASTCT) consensus grading (Lee et al 2019).
^b Resume dose as recommended in Table 3.
^c For daily monitoring, patients should remain within proximity of a healthcare facility.

Table 2 - Other Toxicity

*Resume dose as recommended in Table 3.

Table 3 - Restarting Doses After Dose Delay

No dose adjustment is required. No overall differences in safety or effectiveness were observed between patients ≥ 65 and ≥ 75 years of age (62% and 19% of patients in clinical trials, respectively) compared to younger patients.

Refer to elranatamab drug monograph(s) for additional details of adverse effects.

Refer to the T-Cell Engaging Antibodies guideline for a detailed description of CRS, ICANS and their management.

Refer to elranatamab drug monograph(s) for additional details

• Elranatamab may cause transient suppression of CYP450 enzymes. Monitor and adjust doses of CYP450 substrates with narrow therapeutic index (e.g. warfarin, cyclosporine) as necessary, especially during the step-up dosing schedule, and up to 7 days after a CRS event.

Refer to elranatamab drug monograph(s) for additional details

Administration

• Elranatamab should be administered by subcutaneous injection only.
• Elranatamab vials do not require dilution. Refer to product monograph for details on preparation.
• Allow vials to come to room temperature before administration. Do not warm solution.
• Inject into abdomen (preferred); may be injected at other sites (e.g. thigh). Do not inject into areas where skin is red, bruised, scarred, tattooed or not intact.
• Monitor patients daily for 48 hours after administration of step-up doses for signs and symptoms of CRS or ICANS. Refer to the T-Cell Engaging Antibodies guideline for more information.
• Store unopened vials refrigerated (2°C to 8°C) and protect from light.

Contraindications

• Patients who are hypersensitive to this drug or to any of its components.

Warnings / Precautions

• Serious and life-threatening CRS and ICANS have occurred with elranatamab; ensure step-up schedule is followed and infusions are administered where there is immediate access to medications and equipment required to manage CRS and ICANS.
• Patients should avoid driving or operating heavy machinery for 48 hours following each dose in the step-up dosing schedule, or if any new neurological symptoms present due to the risk of a depressed level of consciousness from ICANS.
• Vaccination with live virus vaccines is not recommended for at least 4 weeks prior to, during and for at least 4 weeks after treatment with elranatamab. The risk of vaccine-associated infection may be increased or immune response to vaccines may be reduced.
• Patients with conditions such as active infection, stem cell transplant (within 12 weeks), history of Guillain-Barre syndrome, or sensory or motor neuropathy (Grade ≥ 2) were excluded from clinical trials; assess benefit-risk of elranatamab treatment in these patients.

Pregnancy / Lactation

• This regimen is not recommended for use in pregnancy. 
  • Adequate contraception should be used by patients and their partners while on treatment and after the last treatment dose. Recommended methods and duration of contraception may differ depending on the treatment. Refer to the drug monograph(s) for more information.

• Consider assessment of immunoglobulin levels in newborns of patients treated with elranatamab.
• Breastfeeding is not recommended during this treatment and after the last treatment dose. Refer to the drug monograph(s) for recommendations after the last treatment dose (if available).
• Fertility effects: Unknown

Treating physicians may decide to monitor more or less frequently for individual patients but should always consider recommendations from the product monograph.

Refer to the hepatitis B virus screening and management guideline for monitoring during and after treatment.

Refer to the T-Cell Engaging Antibodies guideline for monitoring of CRS and ICANS during and after treatment. 

Recommended Clinical Monitoring

Elranatamab drug monograph, Ontario Health (Cancer Care Ontario)

Lee W, Santomasso BD, Locke FL, et al. ASTCT consensus grading for cytokine release Syndrome and neurologic toxicity associated with immune effector cells. Biol Blood Marrow Transplant. 2019;25:625-38.

Lesokhin AM, Tomasson MH, Arnulf B, et al. Elranatamab in relapsed or refractory multiple myeloma: phase 2 MagnetisMM-3 trial results. Nat Med. 2023 Sep;29(9):2259-67.