Teclistamab-cqyv is a bispecific T-cell engaging (BiTE) antibody that binds the CD3 receptor expressed on the surface of T-cells with the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. It is indicated for the treatment of adults with relapsed or refractory multiple myeloma who have received at least 4 prior lines of therapy including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. Teclistamab has a black box warning for cytokine release syndrome and severe neurologic toxicity. It is available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the TECVAYLI and TALVEY REMS. Information for this program enrollment is available at www.TEC-TALREMS.com or 1-855-810-8064.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Confirm the product selection prior to removing teclistamab-cqyv (Tecvayli) from the refrigerator; there is a potential for mix-ups between the products teclistamab-cqyv (Tecvayli) and talquetamab-tgvs (Talvey). Consider carrying only one of these products, storing these products separately, and/or adding auxiliary warning labels on the product containers and storage bins to prevent incorrect product selection.
Route-Specific Administration
Injectable Administration
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.
Subcutaneous Administration
-Teclistamab is administered by a health care professional in a facility with medical personnel and equipment capable of managing severe reactions.
-Verify correct product selection; there is a potential for mix-ups between the teclistamab-cqyv (Tecvayli) and talquetamab-tgvs (Talvey) products.
-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.
Infections, including opportunistic infections, have been reported with teclistamab therapy. Monitor patients for signs and symptoms of infection prior to and during teclistamab therapy; treat appropriately. Therapy interruption or permanent discontinuation may be necessary in patients who develop an infection. Severe (grade 3 or 4, 35%) or fatal (4.2%) infection was reported in patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165). Specific infections reported in this trial were upper respiratory tract infection (26%; grade 3, 2.4%), pneumonia (24%; grade 3 or 4, 15%), and urinary tract infection including cystitis (11%; grade 3, 5%). Sepsis and new onset or reactivated viral infections (including adenovirus, hepatitis B virus, cytomegalovirus, varicella zoster virus, and herpes simplex virus) occurred in less than 10% of patients in this trial. Additionally, fatal infection events included COVID-19 infection (1.8%), pneumonia (1.8%), and septic shock (0.6%). The term upper respiratory tract infection included bronchitis, influenza-like illness, nasopharyngitis/pharyngitis, rhinitis, rhinovirus infection, sinusitis, and tracheitis.
Musculoskeletal pain (44%; grade 3, 4.2%) and bone pain (16%; grade 3, 3%) occurred in patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165). The term musculoskeletal pain included arthralgia, back pain, muscle discomfort, musculoskeletal or non-cardiac chest pain, myalgia, neck pain, and pain in extremity.
Pain was reported in 15% (grade 3, 1.8%) of patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165). The term pain included ear pain/otalgia, flank pain, groin pain, oropharyngeal pain, jaw pain, toothache/dental pain, and tumor pain.
Nausea (25%; grade 3, 0.6%), diarrhea (21%; grade 3, 2.4%), constipation (18%), vomiting (12%; grade 3, 0.6%), and anorexia/decreased appetite (11%; grade 3, 0.6%) occurred in patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165).
Fever (76%; grade 3, 3%) and chills (16%) occurred in patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165).
Edema was reported in 13% of patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165). The term edema included face edema, fluid overload, fluid retention, peripheral edema, and peripheral swelling.
Fatigue including asthenia occurred in 33% (grade 3, 2.4%) of patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165).
Hypotension (18%; grade 3, 1.2%) and hypertension including essential hypertension (12%; grade 3, 4.8%) occurred in patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165).
Bleeding occurred in 12% (grade 3 or 4, 1.8%) of patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165); fatal hemoperitoneum/intraperitoneal hemorrhage was reported in 1 patient (0.6%). The term bleeding included conjunctival/ocular hemorrhage, epistaxis, hematoma and subdural hematoma, hematuria, hemoperitoneum, hemorrhoidal bleeding, lower GI bleeding, melena, and mouth hemorrhage.
Systemic and local allergic reactions have been reported with teclistamab therapy. Therapy interruption or permanent discontinuation may be necessary in patients who develop a severe allergic reaction. Injection site reaction (37%; grade 3, 0.6%) and administration-related reactions (1.2%), specifically mild fever and swollen tongue, occurred in patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165). The term injection site reaction included injection site bruising, cellulitis, discomfort, erythema, hematoma, induration, inflammation, edema, pruritus, rash, and swelling.
Hypoxia (18%; grade 3 or 4, 1.8%) and cough including upper-airway cough syndrome (15%) occurred in patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165).
Cardiac arrhythmia was reported in 16% (grade 3 or 4, 1.8%) of patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165). The term cardiac arrhythmia includes atrial flutter, cardiac arrest, sinus bradycardia, sinus tachycardia, supraventricular tachycardia (SVT), and ventricular tachycardia.
Acute kidney injury including renal impairment occurred in 11% (grade 3 or 4, 3.6%) of patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165); fatal acute renal failure was reported in 1 patient (0.6%). Additionally, increased serum creatinine level that worsened from baseline was reported in 30% (grade 3 or 4, 3%) of patients in this trial.
Hypoalbuminemia/decreased albumin level that worsened from baseline was reported in 68% (grade 3 or 4, 6%) of patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165).
Hyponatremia/decreased sodium level (35%; grade 3 or 4, 10%), hypocalcemia/decreased corrected calcium level (31%; grade 3 or 4, 1.2%), and hypophosphatemia/decreased phosphorus level (38%; grade 3 or 4, 13%) that worsened from baseline occurred in patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165). Additionally, 1 patient permanently discontinued teclistamab therapy due to hypercalcemia.
Myelosuppression has been reported with teclistamab therapy. Evaluate complete blood cell counts at baseline and periodically during treatment; provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Therapy interruption may be necessary in patients who develop severe myelosuppression. Lymphopenia/decreased lymphocyte count (92%; grade 3 or 4, 84%), leukopenia/decreased white blood cell count (86%; grade 3 or 4, 41%), neutropenia/decreased neutrophil count (84%; grade 3 or 4, 56%), thrombocytopenia/decreased platelet count (71%; grade 3 or 4, 22%), and anemia/decreased hemoglobin level (67%; grade 3 or 4, 33%) levels that worsened from baseline and febrile neutropenia (3%) occurred in patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165).
Hypogammaglobulinemia including hypoglobulinemia occurred in 11% (grade 3, 1.2%) of patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165). Monitor immunoglobulin levels during therapy. Manage immunoglobulin deficiency with infection precautions, prophylactic antibiotic/viral therapy, and immunoglobulin replacement per standard guidelines.
Cytokine release syndrome (CRS) has been reported with teclistamab therapy. Signs and symptoms of CRS include fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated AST and ALT levels. Evaluate for and treat other causes of fever, hypoxia, and hypotension. Consider laboratory testing to monitor for disseminated intravascular coagulation (DIC), hematology parameters, as well as pulmonary, cardiac, renal, and hepatic function. 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. CRS was reported in 72% (grade 3, 0.6%) of patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165); recurrent CRS occurred in 33% of patients. Most patients experienced CRS during the step-up dosing period (step-up dose 1, 42%; step-up dose 2, 35%; first treatment dose, 24%); less than 3% of patients had CRS following subsequent treatment doses. The median time to CRS onset was 2 (range, 1 to 6) days after the most recent dose with a median duration of 2 (range, 1 to 9) days.
Neurologic toxicity including immune effector cell-associated neurotoxicity syndrome (ICANS) has been reported with teclistamab therapy. Rule out other causes of neurologic symptoms. 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. ICANS may occur concurrently with cytokine release syndrome (CRS) or after CRS resolves. The most frequent clinical manifestations of ICANS reported were confusion and dysgraphia. Neurotoxicity occurred in 57% (grade 3 or 4, 2.4%) of patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165). Specific neurologic events reported in this trial were headache (25%; grade 3, 0.6%), motor dysfunction (16%), sensory peripheral neuropathy (15%; grade 3, 1.2%), encephalopathy (13%), seizures (less than 10%), Guillain-Barre syndrome (less than 10%), and ICANS (6%). Grade 4 seizure and fatal Guillain-Barre syndrome occurred in 1 patient each in this trial. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS during the step-up dosing period (step-up dose 1, 1.2%; step-up dose 2, 0.6%; first treatment dose, 1.8%). The median time to ICANS onset was 4 (range, 2 to 8) days after the most recent dose with a median duration of 3 (range, 1 to 20) days.
Severe and fatal hepatotoxicity has been reported with teclistamab therapy. Monitor liver function tests at baseline and during treatment as clinically indicated. Elevated hepatic enzymes may occur with or without concurrent cytokine release syndrome. Therapy interruption or permanent discontinuation may be necessary in patients who develop severe hepatotoxicity. Elevated hepatic enzymes including increased gamma-glutamyl transferase (37%; grade 3 or 4, 8%), alkaline phosphatase (42%; grade 3 or 4, 2.4%), AST (34%; grade 3 or 4, 1.2%), and ALT (28%; grade 3 or 4, 1.8%) levels and hyperbilirubinemia/increased total bilirubin level (6%; grade 3 or 4, 0.6%) that worsened from baseline and hepatic failure (less than 10%) occurred in patients with relapsed or refractory multiple myeloma who received teclistamab in a clinical trial (n = 165); fatal hepatic failure was reported in 1 patient.
Antibody formation occurred in 1 patient (0.5%) who received subcutaneous teclistamab in a clinical study (n = 186). Due to the low incidence, it is not known if antibody formation results in changes in teclistamab effectiveness.
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.
Because of the risk of depressed level of consciousness with teclistamab therapy, advise patients to avoid driving or operating machinery or performing other dangerous duties during and for 48 hours following the step-up dosing schedule and following the onset of any neurologic toxicity symptoms until toxicity resolves.
Because of the risk of cytokine release syndrome and neurological toxicities, use requires an experienced clinician with training in the management of these toxicities. Teclistamab administration also requires a specialized care setting that is enrolled in the TECVAYLI and TALVEY REMS program and can comply with all program requirements.
Severe infections have been reported with teclistamab therapy; some cases were fatal or life-threatening. Do not administer teclistamab therapy in patients who have an active infection during the step-up dosing schedule. Administer prophylactic antibiotics as recommended according to clinical guidelines. Consider antiviral prophylaxis for herpes zoster reactivation prior to starting teclistamab therapy. Monitor patients for signs and symptoms of infection prior to and during teclistamab therapy; treat appropriately. Therapy interruption or permanent discontinuation may be necessary in patients who develop an infection. Hypogammaglobulinemia has been reported with teclistamab therapy. Monitor immunoglobulin levels during therapy; manage immunoglobulin deficiency with infection precautions, prophylactic antibiotic/viral therapy, and immunoglobulin replacement per standard guidelines.
Hematologic toxicity (e.g., anemia, neutropenia, febrile neutropenia, and thrombocytopenia) has been reported with teclistamab therapy. Evaluate complete blood cell counts at baseline and periodically during treatment; provide supportive care per local institutional guidelines. Monitor patients with neutropenia for signs of infection. Therapy interruption may be necessary in patient who develop severe myelosuppression.
Hepatotoxicity (e.g., elevated hepatic enzymes, hepatic failure) has been reported with teclistamab therapy. Monitor liver function tests at baseline and during treatment as clinically indicated. Elevated hepatic enzymes may occur with or without concurrent CRS. Therapy interruption or permanent discontinuation may be necessary in patients who develop severe hepatic disease.
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.
Counsel patients about the reproductive risk and contraception requirements during teclistamab treatment. Pregnancy testing should be performed prior to starting teclistamab in patients of reproductive potential. These patients should use effective contraception during and for 5 months after the last teclistamab dose.
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.
For the treatment of multiple myeloma:
NOTE: Teclistamab is designated as an orphan drug by the FDA for this indication.
-for the treatment of relapsed or refractory multiple myeloma in patients who have received at least 4 prior therapies, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody:
Subcutaneous dosage:
Adults: 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. In patients who achieve and maintain a complete response or better for a minimum of 6 months, the dosing frequency may be decreased to 1.5 mg/kg every 2 weeks 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.
Therapeutic Drug Monitoring:
Recommendations for Restarting Therapy After Dose Delay
Step-up dose 1
-More than 7 days since last dose: Restart at step-up dose 1 (0.06 mg/kg). Administer pretreatment medications prior to dose.
Step-up dose 2
-8 to 28 days since last dose: Repeat step-up dose 2 (0.3 mg/kg) and continue step-up dosing schedule. Administer pretreatment medications prior to dose.
-More than 28 days since last dose: Restart at step-up dose 1 (0.06 mg/kg). Administer pretreatment medications prior to dose. Consider benefit versus risks of restarting therapy if delay was due to an adverse reaction.
Treatment doses
-28 days or less since last dose: Continue at last treatment dose and schedule.
-More than 28 days since last dose: Restart at step-up dose 1 (0.06 mg/kg). Administer pretreatment medications prior to dose. Consider benefit versus risks of restarting therapy if delay was due to an adverse reaction.
Management of Treatment-Related Toxicity
Cytokine Release Syndrome (CRS)
NOTE: Fever may be masked by interventions such as antipyretics or anticytokine therapy and may not always be present concurrently with hypotension or hypoxia.
Grade 1 toxicity (temperature of 38 degrees C [100.4 degrees F] or higher attributed to CRS): Hold teclistamab until CRS resolves. Administer pretreatment medications prior to next dose.
Grade 2 toxicity (temperature of 38 degrees C [100.4 degrees F] or higher attributed to CRS with the following: hypotension responsive to fluids and not requiring vasopressors and/or oxygen requirement of low-flow [6 L or less] nasal cannula or blow-by): Hold teclistamab until CRS resolves. Administer pretreatment medications prior to next dose. Hospitalization for 48 hours is recommended following the next dose.
Grade 3 toxicity (temperature of 38 degrees C [100.4 degrees F] or higher attributed to CRS with the following: hypotension requiring one vasopressor with or without vasopressin and/or oxygen requirement of high-flow [more than 6 L] nasal cannula, facemask, non-rebreather mask, or Venturi mask)
-First occurrence and duration lasting less than 48 hours: Hold teclistamab until CRS resolves; provide supportive therapy which may include intensive care. Administer pretreatment medications prior to next dose. Hospitalization for 48 hours is recommended following the next dose.
-Recurrence or duration lasting 48 hours or more: Permanently discontinue teclistamab; provide supportive therapy which may include intensive care.
Grade 4 toxicity (temperature of 38 degrees C [100.4 degrees F] or higher attributed to CRS with the following: hypotension requiring multiple vasopressors (excluding vasopressin) and/or oxygen requirement of positive pressure [e.g., continuous positive airway pressure, bilevel positive airway pressure, intubation, and mechanical ventilation]): Permanently discontinue teclistamab; provide supportive therapy which may include intensive care.
Hematologic Toxicity
Anemia
Hemoglobin level less than 8 g/dL: Hold teclistamab until the hemoglobin level is 8 g/dL or higher.
Neutropenia
Absolute neutrophil count (ANC) less than 0.5 X 109 cells/L: Hold teclistamab until the ANC is 0.5 X 109 cells/L or higher.
Febrile neutropenia: Hold teclistamab until the ANC is 1 X 109 cells/L or higher and fever resolves.
Thrombocytopenia
Platelet count less than 25,000 cells/microliters (mcL) OR platelet count between 25,000 and 50,000 cells/mcL with bleeding: Hold teclistamab until the platelet count is 25,000 cells/mcL or higher with no evidence of bleeding.
Infection
Any grade toxicity: Hold teclistamab in patients with active infection during the step-up dosing schedule
Grade 3 toxicity: Hold subsequent teclistamab doses (i.e., doses administered after the step-up dosing schedule) until the infection improves to grade 1 or less
Grade 4 toxicity: Consider permanently discontinuing teclistamab. If therapy is continued, hold subsequent teclistamab doses (i.e., doses administered after the step-up dosing schedule) until the toxicity infection to grade 1 or less.
Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS)
NOTE: Consider a neurology (or other applicable specialty) consult for further evaluation and management (e.g., non-sedating, anti-seizure medication for seizure prophylaxis) in patients who develop any grade ICANS toxicity.
Immune Effector Cell-Associated Encephalopathy (ICE) Assessment
NOTE: Patients that are unarousable and unable to perform ICE assessment receive no points.
Orientation (oriented to year, month, city, hospital): 4 points
Naming (name 3 objects, e.g., point to clock, pen, button): 3 points
Following commands (e.g., show me 2 fingers OR close your eyes and stick out your tongue): 1 point
Writing (ability to write a standard sentence): 1 point
Attention (count backwards from 100 by ten): 1 point
Grade 1 toxicity (ICE score of 7, 8, or 9 or depressed level of consciousness [awakens spontaneously]): Hold teclistamab until ICANS resolves.
Grade 2 toxicity (ICE score of 3, 4, 5, or 6 or depressed level of consciousness [awakens to voice]): Hold teclistamab until ICANS resolves. Administer dexamethasone 10 mg IV (or equivalent) every 6 hours until symptoms resolve to grade 1 or less, then begin a corticosteroid taper. Hospitalization for 48 hours is recommended following the next dose.
Grade 3 toxicity (ICE score of 0, 1, or 2; depressed level of consciousness [awakens only to tactile stimulus]; any clinical seizure [rapidly resolving focal or generalized seizure OR a non-convulsive seizure on electroencephalogram that resolve with intervention]; or raised intracranial pressure [focal/local edema on neuroimaging])
-First occurrence: Manage the same as with grade 2 toxicity. Provide supportive therapy which may include intensive care.
-Recurrence: Permanently discontinue teclistamab. Administer dexamethasone 10 mg IV (or equivalent) every 6 hours until symptoms resolve to grade 1 or less, then begin a corticosteroid taper. Provide supportive therapy which may include intensive care.
Grade 4 toxicity (ICE score of 0; depressed level of consciousness [unarousable or requires vigorous or repetitive tactile stimuli to arouse, or stupor or coma]; seizures [life-threatening prolonged seizure lasting more than 5 minutes or repetitive clinical or electrical seizures without return to baseline in between]; motor findings [deep focal motor weakness such as hemiparesis or paraparesis]; or raised intracranial pressure/cerebral edema [signs/symptoms of diffuse cerebral edema on neuroimaging, decerebrate or decorticate posturing, cranial nerve VI palsy, papilledema, or Cushing triad]): Permanently discontinue teclistamab. Administer dexamethasone 10 mg IV (or equivalent) every 6 hours until symptoms resolve to grade 1 or less, then begin a corticosteroid taper. Alternatively, consider methylprednisolone 1,000 mg IV daily continuing for 2 or more days. Provide supportive therapy which may include intensive care.
Neurologic Toxicity (Excluding ICANS)
Grade 1 toxicity: Hold teclistamab until neurotoxicity symptoms resolve or stabilize.
Grade 2 toxicity: Hold teclistamab until neurotoxicity symptoms improve to grade 1 or less; provide supportive therapy as required.
Grade 3 toxicity: For first occurrence, hold teclistamab until neurotoxicity symptoms improve to grade 1 or less; provide supportive therapy as required. For recurrence, permanently discontinue teclistamab and provide supportive therapy which may include intensive care.
Grade 4 toxicity: Permanently discontinue teclistamab and provide supportive therapy which may include intensive care.
Other Non-Hematologic Toxicity
Grade 3 toxicity: Hold teclistamab until the toxicity improves to grade 1 or less.
Grade 4 toxicity: Consider permanently discontinuing teclistamab. If therapy is continued, hold subsequent teclistamab doses (i.e., doses administered after the step-up dosing schedule) until the toxicity improves to grade 1 or less.
Maximum Dosage Limits:
-Adults
1.5 mg/kg per week subcutaneously.
-Geriatric
1.5 mg/kg per week subcutaneously.
-Adolescents
Safety and efficacy not established.
-Children
Safety and efficacy not established.
-Infants
Safety and efficacy not established.
Patients with Hepatic Impairment Dosing
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.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no initial dosage adjustments are needed.
*non-FDA-approved indication
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.
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 weekly dose. Teclistamab has a geometric mean clearance of 0.472 L/day (CV, 64%) at the thirteenth weekly dose.
Affected cytochrome P450 isoenzymes and drug transporters: CYP substrates
Teclistamab may cause a cytokine release that suppresses CYP enzyme activity and increases the exposure of CYP substrates.
-Route-Specific Pharmacokinetics
Subcutaneous Route
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 weekly 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.
-Special Populations
Hepatic Impairment
Mild hepatic impairment (total bilirubin level less than or equal to the ULN with AST level greater than the ULN OR total bilirubin level greater than 1 to 1.5 times the ULN with any AST level) does not significantly impact the pharmacokinetic (PK) parameters of teclistamab. The effect of moderate to severe hepatic impairment (total bilirubin level more than 1.5 times ULN with any AST level) on the PK parameters of teclistamab is unknown.
Renal Impairment
Mild or moderate renal impairment (estimated glomerular filtration rate [eGFR] of 30 to 89 mL/min, using the Modification of Diet in Renal Disease method) does not significantly impact the pharmacokinetic (PK) parameters of teclistamab. The effect of severe renal impairment (eGFR less than 30 mL/min) on the PK parameters of teclistamab is unknown.
Geriatric
Age (range, 24 to 84 years) does not significantly impact the pharmacokinetic parameters of teclistamab.
Gender Differences
Sex does not significantly impact the pharmacokinetic parameters of teclistamab.
Ethnic Differences
Race (White, Black or African American) or ethnicity (Hispanic/Latino or not Hispanic/Latino) does not significantly impact the pharmacokinetic parameters of teclistamab.
Obesity
Increased body weight (range, 41 to 139 kg) correlates with increased volume of distribution and clearance of teclistamab.