teclistamab

Antineoplastic Bispecific Antibodies Targeting BCMA and CD3

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Teclistamab is a clear to slightly opalescent, colorless to light yellow solution; do not use if the solution is discolored, cloudy, or contains foreign particles.

Teclistamab is administered by a health care professional in a facility with medical personnel and equipment capable of managing severe reactions.
Premedicate patients with a corticosteroid, H1-antihistamine (e.g., diphenhydramine), and acetaminophen approximately 1 to 3 hours prior to the injection as recommended.
Preparation:
Teclistamab is available as single-use 30 mg/3 mL (10 mg/mL) or 153 mg/1.7 mL (90 mg/mL) solution vials; do not combine vials of different concentrations to achieve the dose.
Further vial dilution is not necessary; teclistamab is compatible with stainless steel injection needles and polypropylene or polycarbonate syringe material.
Remove the appropriate concentration and number of vials from the refrigerator and allow the vial(s) to warm to ambient temperature (15 to 30 degrees C; 59 to 86 degrees F) for at least 15 minutes; do not warm the vial(s) any other way.
Once equilibrated, gently swirl the vial(s) for approximately 10 seconds to mix; do not shake.
Using aseptic technique, withdraw the required injection volume from the vial(s) into a syringe using a transfer needle.
The injection volume should not exceed 2 mL; divide doses that require more than 2 mL equally into multiple syringes.
The appropriate injection volume is based on vial concentration, patient weight, and type of dose as follows:
30 mg/3 mL vial (10 mg/mL) - Use for step-up doses 1 and 2
35 to 39 kg: step-up dose 1, 2.2 mg (0.22 mL); step-up dose 2, 11 mg (1.1 mL)40 to 44 kg: step-up dose 1, 2.5 mg (0.25 mL); step-up dose 2, 13 mg (1.3 mL)45 to 49 kg: step-up dose 1, 2.8 mg (0.28 mL); step-up dose 2, 14 mg (1.4 mL)50 to 59 kg: step-up dose 1, 3.3 mg (0.33 mL); step-up dose 2, 16 mg (1.6 mL)60 to 69 kg: step-up dose 1, 3.9 mg (0.39 mL); step-up dose 2, 19 mg (1.9 mL)70 to 79 kg: step-up dose 1, 4.5 mg (0.45 mL); step-up dose 2, 22 mg (2.2 mL)80 to 89 kg: step-up dose 1, 5.1 mg (0.51 mL); step-up dose 2, 25 mg (2.5 mL)90 to 99 kg: step-up dose 1, 5.7 mg (0.57 mL); step-up dose 2, 28 mg (2.8 mL)100 to 109 kg: step-up dose 1, 6.3 mg (0.63 mL); step-up dose 2, 31 mg (3.1 mL)*110 to 119 kg: step-up dose 1, 6.9 mg (0.69 mL); step-up dose 2, 34 mg (3.4 mL)*120 to 129 kg: step-up dose 1, 7.5 mg (0.75 mL); step-up dose 2, 37 mg (3.7 mL)*130 to 139 kg: step-up dose 1, 8.1 mg (0.81 mL); step-up dose 2, 40 mg (4 mL)*140 to 149 kg: step-up dose 1, 8.7 mg (0.87 mL); step-up dose 2, 43 mg (4.3 mL)*150 to 160 kg: step-up dose 1, 9.3 mg (0.93 mL); step-up dose 2, 47 mg (4.7 mL)**Requires 2 vials for dose
153 mg/1.7 mL vial (90 mg/mL) - Use for treatment doses
35 to 39 kg: 56 mg (0.62 mL)40 to 44 kg: 63 mg (0.7 mL)45 to 49 kg: 70 mg (0.78 mL)50 to 59 kg: 82 mg (0.91 mL)60 to 69 kg: 99 mg (1.1 mL)70 to 79 kg: 108 mg (1.2 mL)80 to 89 kg: 126 mg (1.4 mL)90 to 99 kg: 144 mg (1.6 mL)100 to 109 kg: 153 mg (1.7 mL)110 to 119 kg: 171 mg (1.9 mL)*120 to 129 kg: 189 mg (2.1 mL)*130 to 139 kg: 198 mg (2.2 mL)*140 to 149 kg: 216 mg (2.4 mL)*150 to 160 kg: 234 mg (2.6 mL)**Requires 2 vials for dose
Storage of prepared syringe(s): if not used immediately, store syringe(s) at 2 to 8 degrees C (36 to 46 degrees F) or at ambient temperature (15 to 30 degrees C; 59 to 86 degrees F) for a maximum of 20 hours; discard syringe(s) not used after 20 hours.
Subcutaneous injection:
Replace the transfer needle with an appropriately sized needle for a subcutaneous injection.
Inject the teclistamab dose into the subcutaneous tissue of the abdomen (preferred site) or other appropriate site (e.g., thigh).
Space injections at least 2 cm apart if multiple injections are required for the dose.
Do not inject into tattoos, scars, or areas where the skin is red, bruised, tender, hard, or not intact.

lymphopenia / Delayed / 84.0-84.0
neutropenia / Delayed / 56.0-56.0
leukopenia / Delayed / 41.0-41.0
infection / Delayed / 0-35.0
thrombocytopenia / Delayed / 22.0-22.0
hypophosphatemia / Delayed / 13.0-13.0
hyponatremia / Delayed / 10.0-10.0
seizures / Delayed / 0-10.0
Guillain-Barre syndrome / Delayed / 0-10.0
hepatic failure / Delayed / 0-10.0
elevated hepatic enzymes / Delayed / 0-8.0
hypoalbuminemia / Delayed / 6.0-6.0
hypertension / Early / 4.8-4.8
musculoskeletal pain / Early / 4.2-4.2
bone pain / Delayed / 3.0-3.0
fever / Early / 3.0-3.0
diarrhea / Early / 2.4-2.4
fatigue / Early / 2.4-2.4
neurotoxicity / Early / 2.4-2.4
bleeding / Early / 1.8-1.8
hypoxia / Early / 1.8-1.8
hypotension / Rapid / 1.2-1.2
hypocalcemia / Delayed / 1.2-1.2
hypogammaglobulinemia / Delayed / 1.2-1.2
peripheral neuropathy / Delayed / 1.2-1.2
anorexia / Delayed / 0.6-0.6
nausea / Early / 0.6-0.6
vomiting / Early / 0.6-0.6
injection site reaction / Rapid / 0.6-0.6
cytokine release syndrome / Rapid / 0.6-0.6
hyperbilirubinemia / Delayed / 0.6-0.6
ocular hemorrhage / Delayed / Incidence not known
GI bleeding / Delayed / Incidence not known
ventricular tachycardia / Early / Incidence not known
cardiac arrest / Early / Incidence not known
atrial flutter / Early / Incidence not known
bradycardia / Rapid / Incidence not known
renal failure / Delayed / Incidence not known

constipation / Delayed / 18.0-18.0
edema / Delayed / 13.0-13.0
encephalopathy / Delayed / 13.0-13.0
antibody formation / Delayed / 0.5-0.5
cystitis / Delayed / Incidence not known
tracheitis / Delayed / Incidence not known
flank pain / Delayed / Incidence not known
peripheral edema / Delayed / Incidence not known
fluid retention / Delayed / Incidence not known
hematoma / Early / Incidence not known
subdural hematoma / Early / Incidence not known
hematuria / Delayed / Incidence not known
melena / Delayed / Incidence not known
sinus tachycardia / Rapid / Incidence not known
supraventricular tachycardia (SVT) / Early / Incidence not known
hypercalcemia / Delayed / Incidence not known
confusion / Early / Incidence not known

headache / Early / 24.4-24.4
chills / Rapid / 16.0-16.0
cough / Delayed / 15.0-15.0
sinusitis / Delayed / Incidence not known
pharyngitis / Delayed / Incidence not known
influenza / Delayed / Incidence not known
rhinitis / Early / Incidence not known
arthralgia / Delayed / Incidence not known
back pain / Delayed / Incidence not known
myalgia / Early / Incidence not known
otalgia / Early / Incidence not known
dental pain / Delayed / Incidence not known
asthenia / Delayed / Incidence not known
epistaxis / Delayed / Incidence not known

Cytokine release syndrome (CRS) has been reported with teclistamab; some cases were fatal or life-threatening. Evaluate for and treat other causes of fever, hypoxia, and hypotension. To reduce the risk of CRS, administer teclistamab according to a step-up dosing schedule and give pretreatment medications as follows: dexamethasone 16 mg PO/IV or equivalent, diphenhydramine 50 mg PO/IV or equivalent, and acetaminophen 650 mg PO/IV or equivalent at 1 to 3 hours prior to each dose in the step-up dosing schedule. Continue premedications with subsequent teclistamab doses in patients who experienced CRS after a prior dose; restart premedications in patients who repeat doses within the step-up dosing schedule following a dose delay. Hospitalization is recommended for 48 hours following each dose in the step-up dosing schedule. Interruption or discontinuation of therapy may be necessary in patients who develop CRS; evaluate the need for hospitalization, supportive care, and further management (using current practice guideline) in patients with severe CRS.

Severe neurotoxicity (e.g., immune effector cell-associated neurotoxicity syndrome (ICANS), encephalopathy, seizures, and Guillain-Barre syndrome) has been reported with teclistamab therapy; some cases were fatal or life-threatening. Rule out other causes of neurologic symptoms. ICANS may occur concurrently with cytokine release syndrome (CRS) or after CRS resolves. Hospitalization is recommended for 48 hours following each dose in the step-up dosing schedule. Monitor patients for signs and symptoms of neurologic toxicity during treatment. Therapy interruption, corticosteroid administration, or permanent discontinuation of therapy may be necessary in patients who develop neurotoxicity; consider a neurology (or other applicable specialty) consult for further evaluation and management (e.g., non-sedating, anti-seizure medication for seizure prophylaxis). Evaluate the need for hospitalization, supportive care, and further management (using current practice guideline) in patients with severe neurotoxicity.

TECVAYLI

Rx

Bispecific B-cell maturation antigen-directed CD3 T-cell engaging antibody
Used in adult patients with heavily pretreated relapsed or refractory multiple myeloma
Boxed warning for cytokine release syndrome and severe neurologic toxicity

Step-up dosing schedule: dose 1, 0.06 mg/kg subcutaneously on day 1; dose 2, 0.3 mg/kg subcutaneously on day 4 (may give 2 to 4 days after step-up dose 1 and up to 7 days after step-up dose 1 to allow for resolution of adverse reactions); and first treatment dose, 1.5 mg/kg subcutaneously on day 7 (may give 2 to 4 days after step-up dose 2 and up to 7 days after step-up dose 2 to allow for resolution of adverse reactions). Begin the weekly dosing schedule starting 1 week after the first treatment dose as follows: 1.5 mg/kg subcutaneously once weekly until disease progression. Therapy interruption or discontinuation may be necessary in patients who develop toxicity. Administer premedications (dexamethasone 16 mg PO or IV, diphenhydramine 50 mg PO or IV or equivalent, and acetaminophen 650 mg PO or IV or equivalent) at 1 to 3 hours prior to each dose in the step-up dosing schedule. Continue premedications with subsequent teclistamab doses in patients who experienced cytokine release syndrome after a prior dose; restart premedications in patients who repeat doses within the step-up dosing schedule following a dose delay. Consider antiviral prophylaxis for herpes zoster reactivation prior to starting teclistamab therapy. At a median follow-up of 14.1 (range, 0.3 to 24.4) months, the overall response rate was 63% in patients with relapsed or refractory multiple myeloma who received teclistamab in a multicenter, phase 1/2 trial (n = 165). Additionally, 39.4% of patients achieved a complete response or better. The median duration of response was 18.4 months and the median progression-free survival time was 11.3 months. In this study, patients (median age, 64 [range, 33 to 84] years; high-risk cytogenetics, 25.7%) had received a median of 5 (range, 2 to 14) prior lines of therapy; 81.8% of patients had previously received a stem-cell transplantation.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no initial dosage adjustments are needed. Therapy interruption or permanent discontinuation may be necessary in patients who develop severe hepatotoxicity.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no initial dosage adjustments are needed.

Monitor for toxicity and adjust the dose as needed for CYP substrates, especially during the first 2 weeks of teclistamab therapy and during and after cytokine release syndrome. Teclistamab causes a cytokine release that may suppress CYP enzyme activity.

TECVAYLI Subcutaneous Inj Sol: 1mL, 10mg, 90mg

1.5 mg/kg per week subcutaneously.

1.5 mg/kg per week subcutaneously.

Safety and efficacy not established.

Safety and efficacy not established.

Safety and efficacy not established.

Teclistamab-cqyv is a bispecific T-cell engaging (BiTE) antibody that works by binding the CD3 receptor expressed on the surface of T-cells to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells. It is a humanized immunoglobulin G4-proline, alanine, alanine (IgG4-PAA) antibody produced from Chinese Hamster Ovary (CHO) cells using recombinant DNA technology. Teclistamab consists of an anti-BCMA heavy chain and light chain and an anti-CD3 heavy chain and light chain with 2 interchain disulfide bonds connecting the two arms. By binding the CD3 antigen and BCMA, teclistamab causes myeloma cell lysis directly via protein toxin (e.g., perforins and granzymes) release and increased cytokine (e.g., interferons, tumor necrosis factors, and interleukins) production.

Teclistamab is administered subcutaneously. It has a mean volume of distribution of 5.63 L (coefficient of variation (CV), 29%). Its clearance decreases over time with a mean maximal clearance reduction of 40.8% from baseline to the thirteenth dose. Teclistamab has a geometric mean clearance of 0.472 L/day (CV, 64%) at the thirteenth dose.
Affected cytochrome P450 isoenzymes and drug transporters: CYP substratesTeclistamab may cause a cytokine release that suppresses CYP enzyme activity and increases the exposure of CYP substrates.

The mean bioavailability of teclistamab is 72% when administered subcutaneously. The pharmacokinetic parameters of teclistamab increase proportionally over a dosage range of 0.08 to 3 mg/kg (0.05 to 2 times the approved recommended treatment dosage). A 90% steady-state exposure rate was achieved after 12 weekly treatment doses. Following the thirteenth weekly 1.5 mg/kg subcutaneous dose, the teclistamab geometric mean Cmax level was 23.8 mcg/mL (coefficient of variation (CV), 55%), geometric mean AUC(tau) value was 3,838 mcg x hour/mL (CV, 57%), and median Tmax was 72 (range, 24 to 168) hours. Discontinuation of teclistamab after the thirteenth treatment dose is expected to result in a 50% decreased Cmax level at a median time of 15 (range, 7 to 33) days after Tmax and a 97% decreased Cmax level at a median time of 69 (range, 32 to 163) days after Tmax.

Teclistamab may cause fetal harm if administered during pregnancy based on its mechanism of action. Pregnant patients should be apprised of the potential hazard to the fetus. There are no available data with teclistamab use in pregnant women; animal reproductive and developmental toxicity studies have not been conducted. Teclistamab causes T-cell activation and cytokine release; immune activation may compromise pregnancy maintenance. Human immunoglobulin G is known to cross into the placenta; therefore, teclistamab may be transmitted from the mother to the developing fetus. Due to a risk of hypogammaglobulinemia, assess immunoglobulin levels in neonates of mothers treated with teclistamab.

Due to the potential for serious adverse reactions in the breastfed child, advise patients to avoid breast-feeding during and for 5 months after the last teclistamab dose. It is not known if teclistamab is secreted in human milk or if it has effects on milk production or the breastfed child. Human immunoglobulin (IgG) is excreted in human milk; however, the effects of local gastrointestinal exposure and limited systemic exposure in the breastfed child to teclistamab are not known.