TECVAYLI® is a bispecific B-cell maturation antigen (BCMA)-directed CD3 T-cell engager indicated for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody.
This indication is approved under accelerated approval based on response rate. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Contraindications2:
- None.
Warnings and precautions2:
Cytokine release syndrome
TECVAYLI can cause cytokine release syndrome (CRS), including life-threatening or fatal reactions.
In the clinical trial, CRS occurred in 72% of patients who received TECVAYLI at the recommended dose, with Grade 1 CRS occurring in 50% of patients, Grade 2 in 21%, and Grade 3 in 0.6%. Recurrent CRS occurred in 33% of patients. Most patients experienced CRS following step-up dose 1 (42%), step-up dose 2 (35%), or the initial treatment dose (24%). Less than 3% of patients developed first occurrence of CRS following subsequent doses of TECVAYLI. The median time to onset of CRS was 2 (range: 1 to 6) days after the most recent dose with a median duration of 2 (range: 1 to 9) days.
Clinical signs and symptoms of CRS included, but were not limited to, fever, hypoxia, chills, hypotension, sinus tachycardia, headache, and elevated liver enzymes (aspartate aminotransferase and alanine aminotransferase elevation).
Initiate therapy according to TECVAYLI step-up dosing schedule to reduce risk of CRS. Administer pretreatment medications to reduce risk of CRS and monitor patients following administration of TECVAYLI.
At the first sign of CRS, immediately evaluate patient for hospitalization. Administer supportive care based on severity and consider further management per current practice guidelines. Withhold or permanently discontinue TECVAYLI based on severity.
TECVAYLI is available only through a restricted program under a REMS.
Neurologic toxicity including ICANS
TECVAYLI can cause serious, life-threatening or fatal neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS).
In the clinical trial, neurologic toxicity occurred in 57% of patients who received TECVAYLI at the recommended dose, with Grade 3 or 4 neurologic toxicity occurring in 2.4% of patients. The most frequent neurologic toxicities were headache (25%), motor dysfunction (16%), sensory neuropathy (15%), and encephalopathy (13%).
With longer follow-up, Grade 4 seizure and fatal Guillain-Barré syndrome (one patient each) occurred in patients who received TECVAYLI. In the clinical trial, ICANS was reported in 6% of patients who received TECVAYLI at the recommended dose. Recurrent ICANS occurred in 1.8% of patients. Most patients experienced ICANS following step-up dose 1 (1.2%), step-up dose 2 (0.6%), or the initial treatment dose (1.8%). Less than 3% of patients developed first occurrence of ICANS following subsequent doses of TECVAYLI. The median time to onset of ICANS was 4 (range: 2 to 8) days after the most recent dose with a median duration of 3 (range: 1 to 20) days. The most frequent clinical manifestations of ICANS reported were confusional state and dysgraphia. The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS.
Monitor patients for signs and symptoms of neurologic toxicity during treatment. At the first sign of neurologic toxicity, including ICANS, immediately evaluate patient and provide supportive therapy based on severity. Withhold or permanently discontinue TECVAYLI based on severity per recommendations and consider further management per current practice guidelines.
Due to the potential for neurologic toxicity, patients receiving TECVAYLI are at risk of depressed level of consciousness. Advise patients to refrain from driving or operating heavy or potentially dangerous machinery during and for 48 hours after completion of TECVAYLI step-up dosing schedule and in the event of new onset of any neurologic toxicity symptoms until neurologic toxicity resolves.
TECVAYLI is available only through a restricted program under a REMS.
TECVAYLI® AND TALVEY® REMS
TECVAYLI is available only through a restricted program under a REMS called the TECVAYLI and TALVEY REMS because of the risks of CRS and neurologic toxicity, including ICANS.
Notable requirements of the TECVAYLI and TALVEY REMS include the following:
- Prescribers must be certified with the program by enrolling and completing training.
- Prescribers must counsel patients receiving TECVAYLI about the risk of CRS and neurologic toxicity, including ICANS, and provide patients with Patient Wallet Card.
- Pharmacies and healthcare settings that dispense TECVAYLI must be certified with the TECVAYLI and TALVEY REMS program and must verify prescribers are certified through the TECVAYLI and TALVEY REMS program.
- Wholesalers and distributers must only distribute TECVAYLI to certified pharmacies or healthcare settings.
Further information about the TECVAYLI and TALVEY REMS program is available at www.TEC-TALREMS.com or by telephone at 1-855-810-8064.
Hepatotoxicity
TECVAYLI can cause hepatotoxicity, including fatalities. In patients who received TECVAYLI at the recommended dose in the clinical trial, there was one fatal case of hepatic failure. Elevated aspartate aminotransferase (AST) occurred in 34% of patients, with Grade 3 or 4 elevations in 1.2%. Elevated alanine aminotransferase (ALT) occurred in 28% of patients, with Grade 3 or 4 elevations in 1.8%. Elevated total bilirubin occurred in 6% of patients with Grade 3 or 4 elevations in 0.6%. Liver enzyme elevation can occur with or without concurrent CRS.
Monitor liver enzymes and bilirubin at baseline and during treatment as clinically indicated. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.
Infections
TECVAYLI can cause severe, life-threatening, or fatal infections. In patients who received TECVAYLI at the recommended dose in the clinical trial, serious infections, including opportunistic infections, occurred in 30% of patients, with Grade 3 or 4 infections in 35%, and fatal infections in 4.2%.
Monitor patients for signs and symptoms of infection prior to and during treatment with TECVAYLI and treat appropriately. Administer prophylactic antimicrobials according to guidelines.
Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.
Monitor immunoglobulin levels during treatment with TECVAYLI and treat according to guidelines, including infection precautions and antibiotic or antiviral prophylaxis.
Neutropenia
TECVAYLI can cause neutropenia and febrile neutropenia. In patients who received TECVAYLI at the recommended dose in the clinical trial, decreased neutrophils occurred in 84% of patients, with Grade 3 or 4 decreased neutrophils in 56%. Febrile neutropenia occurred in 3% of patients.
Monitor complete blood cell counts at baseline and periodically during treatment and provide supportive care per local institutional guidelines.
Monitor patients with neutropenia for signs of infection. Withhold TECVAYLI based on severity.
Hypersensitivity and other administration reactions
TECVAYLI can cause both systemic administration-related reactions and local injection-site reactions.
Systemic reactions
In patients who received TECVAYLI at the recommended dose in the clinical trial, 1.2% of patients experienced systemic-administration reactions, which included Grade 1 recurrent pyrexia and Grade 1 swollen tongue.
Local reactions
In patients who received TECVAYLI at the recommended dose in the clinical trial, injection-site reactions occurred in 35% of patients with Grade 1 injection-site reactions in 30% and Grade 2 in 4.8%. Withhold TECVAYLI or consider permanent discontinuation of TECVAYLI based on severity.
Embryo-fetal toxicity
Based on its mechanism of action, TECVAYLI may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with TECVAYLI and for 5 months after the last dose.
Adverse reactions
The most common adverse reactions (≥20%) were pyrexia, CRS, musculoskeletal pain, injection site reaction, fatigue, upper respiratory tract infection, nausea, headache, pneumonia, and diarrhea. The most common Grade 3 to 4 laboratory abnormalities (≥20%) were decreased lymphocytes, decreased neutrophils, decreased white blood cells, decreased hemoglobin, and decreased platelets.
DARZALEX FASPRO® is a combination of daratumumab, a CD38-targeted antibody, and hyaluronidase, an endoglycosidase, indicated for the treatment of adult patients with:
- Multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone for induction and consolidation in newly diagnosed patients who are eligible for autologous stem cell transplant
- Multiple myeloma in combination with bortezomib, lenalidomide, and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- Multiple myeloma in combination with bortezomib, melphalan and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
- Multiple myeloma in combination with lenalidomide and dexamethasone in newly diagnosed patients who are ineligible for autologous stem cell transplant and in patients with relapsed or refractory multiple myeloma who have received at least one prior therapy
- Multiple myeloma in combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
- Multiple myeloma in combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
- Multiple myeloma in combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor
- Multiple myeloma in combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
- Multiple myeloma as monotherapy, in patients who have received at least three prior lines of therapy including a proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent
- High-risk smoldering multiple myeloma as monotherapy
- Light chain (AL) amyloidosis in combination with bortezomib, cyclophosphamide and dexamethasone in newly diagnosed patients.
Contraindications3:
- DARZALEX FASPRO® is contraindicated in patients with a history of severe hypersensitivity to daratumumab, hyaluronidase, or any of the components of the formulation.
Warnings and precautions3:
Hypersensitivity and other administration reactions
Both systemic administration-related reactions, including severe or life-threatening reactions, and local injection-site reactions can occur with DARZALEX FASPRO. Fatal reactions have been reported with daratumumab-containing products, including DARZALEX FASPRO.
Systemic reactions
In a pooled safety population of 1446 patients with multiple myeloma (N=1253) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO as monotherapy or as part of a combination therapy, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3%, Grade 3: 0.8%, Grade 4: 0.1%). In patients with high-risk smoldering multiple myeloma (N=193), systemic administration-related reactions occurred in 17% of patients in AQUILA (Grade 2: 7%, Grade 3: 1%).
In all patients (N=1639), systemic administration-related reactions occurred in 7% of patients with the first injection, 0.5% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 3.2 hours (range: 4 minutes to 3.5 days). Of the 283 systemic administration related reactions that occurred in 135 patients, 240 (85%) occurred on the day of DARZALEX FASPRO administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.
Severe reactions include hypoxia, dyspnea, hypertension, and tachycardia, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Other signs and symptoms of systemic administration-related reactions may include respiratory symptoms, such as bronchospasm, nasal congestion, cough, throat irritation, allergic rhinitis, and wheezing, as well as anaphylactic reaction, pyrexia, chest pain, pruritus, chills, vomiting, nausea, hypotension, and blurred vision.
Pre-medicate patients with histamine-1 receptor antagonist, acetaminophen and corticosteroids. Monitor patients for systemic administration-related reactions, especially following the first and second injections. For anaphylactic reaction or life-threatening (Grade 4) administration-related reactions, immediately and permanently discontinue DARZALEX FASPRO. Consider administering corticosteroids and other medications after the administration of DARZALEX FASPRO depending on dosing regimen and medical history to minimize the risk of delayed (defined as occurring the day after administration) systemic administration-related reactions.
Ocular adverse reactions, including acute myopia and narrowing of the anterior chamber angle due to ciliochoroidal effusions with potential for increased intraocular pressure or glaucoma, have occurred with daratumumab-containing products. If ocular symptoms occur, interrupt DARZALEX FASPRO and seek immediate ophthalmologic evaluation prior to restarting DARZALEX FASPRO.
Local reactions
In this pooled safety population of 1446 patients with multiple myeloma (N=1253) or light chain (AL) amyloidosis (N=193), injection-site reactions occurred in 8% of patients, including Grade 2 reactions in 1.1%. The most frequent (>1%) injection-site reactions were injection site erythema and injection site rash. In patients with high-risk smoldering multiple myeloma (N=193), injection-site reactions occurred in 28% of patients, including Grade 2 reactions in 3%. These local reactions occurred a median of 6 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO. Monitor for local reactions and consider symptomatic management.
Cardiac toxicity in patients with light chain (AL) amyloidosis
Serious or fatal cardiac adverse reactions occurred in patients with light chain (AL) amyloidosis who received DARZALEX FASPRO in combination with bortezomib, cyclophosphamide and dexamethasone. Serious cardiac disorders occurred in 16% and fatal cardiac disorders occurred in 10% of patients. Patients with NYHA Class IIIA or Mayo Stage IIIA disease may be at greater risk. Patients with NYHA Class IIIB or IV disease were not studied. Monitor patients with cardiac involvement of light chain (AL) amyloidosis more frequently for cardiac adverse reactions and administer supportive care as appropriate.
Infections
DARZALEX FASPRO can cause serious, life-threatening, or fatal infections. In patients who received DARZALEX FASPRO in a pooled safety population including patients with smoldering multiple myeloma and light chain (AL) amyloidosis (N=1639), serious infections, including opportunistic infections, occurred in 24% of patients, Grade 3 or 4 infections occurred in 22%, and fatal infections occurred in 2.5%. The most common type of serious infection reported was pneumonia (8.5%). Monitor patients for signs and symptoms of infection prior to and during treatment with DARZALEX FASPRO and treat appropriately. Administer prophylactic antimicrobials according to guidelines.
Neutropenia
DARZALEX FASPRO may increase neutropenia induced by background therapy.
Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Monitor patients with neutropenia for signs of infection. Consider withholding DARZALEX FASPRO until recovery of neutrophils. In lower body weight patients receiving DARZALEX FASPRO, higher rates of Grade 3-4 neutropenia were observed.
Thrombocytopenia
DARZALEX FASPRO may increase thrombocytopenia induced by background therapy.
Monitor complete blood cell counts periodically during treatment according to manufacturer’s prescribing information for background therapies. Consider withholding DARZALEX FASPRO until recovery of platelets.
Embryo-fetal toxicity
Based on the mechanism of action, DARZALEX FASPRO can cause fetal harm when administered to a pregnant woman. DARZALEX FASPRO may cause depletion of fetal immune cells and decreased bone density. Advise pregnant women of the potential risk to a fetus. Advise females with reproductive potential to use effective contraception during treatment with DARZALEX FASPRO® and for 3 months after the last dose.
The combination of DARZALEX FASPRO with lenalidomide, thalidomide, or pomalidomide is contraindicated in pregnant women because lenalidomide, thalidomide, and pomalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, thalidomide, or pomalidomide prescribing information on use during pregnancy.
Interference with serological testing
Daratumumab binds to CD38 on RBCs and results in a positive Indirect Antiglobulin Test (Indirect Coombs test). Daratumumab-mediated positive indirect antiglobulin test may persist for up to 6 months after the last daratumumab administration. Daratumumab bound to RBCs masks detection of antibodies to minor antigens in the patient’s serum. The determination of a patient’s ABO and Rh blood type are not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX FASPRO. Type and screen patients prior to starting DARZALEX FASPRO.
Interference with determination of complete response
Daratumumab is a human IgG kappa monoclonal antibody that can be detected on both the serum protein electrophoresis and immunofixation assays used for the clinical monitoring of endogenous M‑protein. This interference can impact the determination of complete response and of disease progression in some DARZALEX FASPRO-treated patients with IgG kappa myeloma protein.
Adverse reactions
In multiple myeloma, the most common adverse reaction (≥20%) with DARZALEX FASPRO monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20% for any combination) include fatigue, nausea, diarrhea, dyspnea, insomnia, headache, rash, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, musculoskeletal pain, upper respiratory tract infection, peripheral neuropathy, peripheral sensory neuropathy, constipation, pneumonia, edema, peripheral edema, and anemia.
The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.
- MajesTEC-3 is multicenter, open-label, study that randomized patients between October 22, 2021, and September 29, 2023, at 150 sites across 20 countries.
- Patients were randomly assigned 1:1 to receive Tec-Dara or investigator’s choice of SoC regimens of DPd/DVd. The Tec-Dara group received 28-day cycles of teclistamab at 1.5 mg/kg weekly in cycle 1 following 2 step-up doses of 0.06 and 0.3 mg/kg; 1.5 mg/kg weekly in cycle 2; 3 mg/kg every 2 weeks in cycles 3 to 6; and 3 mg/kg every 4 weeks from cycle 7 onward, which provides comparable pharmacokinetic exposure as the approved 1.5 mg/kg every 2 weeks. Subcutaneous daratumumab was dosed per the approved dosing schedule.
| 28-day cycles |
Cycle 1a QW |
Cycle 2 QW |
Cycles 3-6 Q2W |
Cycle 7+ Q4W |
|---|---|---|---|---|
| Tec | Tec 1.5 mg/kg (preceded by SUD on Day 2 and 4, and treatment dose on Day 8)b |
Tec 1.5 mg/kg | Tec 3 mg/kg | Tec 3 mg/kg |
| Dara | Dara SC 1800 mg starting from Cycle 1 Day 1 | Dara SC 1800 mg | Dara SC 1800 mg | |
|
aDexamethasone, acetaminophen, and diphenhydramine premedication was required for the first 2 weeks; subsequent dexamethasone was not required thereafter. bPatients received SUD of 0.06 and 0.3 mg/kg on days 2 and 4, respectively, followed by the first treatment dose of 1.5 mg/kg on day 8 and 1.5 mg/kg weekly thereafter. |
||||
- Dose reductions from 3 mg/kg to 1.5 mg/kg or decrease in teclistamab dosing frequency were permitted with sponsor approval. Patients who discontinued ≥1 component of study treatment could continue to receive other components, as assigned.
- Dexamethasone, acetaminophen, and diphenhydramine premedication was required for the first 2 weeks; subsequent dexamethasone was not required.
- The DPd/DVd group received treatment per established schedules.
- Treatment continued until confirmed progressive disease, death, intolerance, or withdrawal of consent.
- Infection prophylaxis, including immunoglobulin supplementation, antibiotics, and prophylaxis for Pneumocystis jirovecii pneumonia and herpes zoster reactivation, was administered by institutional guidelines. Immunoglobulin replacement therapy and infection prophylaxis guidance were reinforced per protocol amendment (February 2023), which affirmed the importance of medical monitoring of immunoglobulin G levels and adherence to protocol-specified immunoglobulin supplementation guidance.
- Tocilizumab was permitted for grade 1 and recommended for grade ≥2 CRS.
Key eligibility criteria1
- Patients had confirmed RRMM
- Patients had received 1-3 prior lines of antimyeloma therapy, including a proteasome inhibitor and lenalidomide, with documented disease progression on or after their last regimen.
- Patients with only 1 prior line of therapy were required to have lenalidomide-refractory myeloma per IMWG criteria
- ECOG PS score of 0-2
- Prior BCMA-directed therapy
- Refractoriness to anti-CD38 mAbs
- Patients with pomalidomide-refractory and bortezomib-refractory myeloma were not allowed to receive DPd and DVd, respectively
Primary endpoints1,4
- PFS as assessed by IRC, defined as the time from the date of randomization to the date of first documented disease progression or death
Key secondary endpoints1
- ≥CR
- ORR
- MRD negativity (10-5 threshold)
- OS
- MySIm-Q TSS
Additional secondary endpoints:
- Safety
- Pharmacokinetics
- Immunogenicity
a“Other” includes Native Hawaiian or Pacific Islander (Tec-Dara, n = 1 [0.3%]; DPd/DVd, n = 0; total, n = 1 [0.2%]), American Indian or Alaska Native (n = 0; n = 1 [0.3%]; n = 1 [0.2%]), not reported (n = 14 [4.8%]; n = 16 [5.4%]; n = 30 [5.1%]), and unknown (n = 5 [1.7%]; n = 2 [0.7%]; n = 7 [1.2%]).
bMaximum value from bone marrow biopsy or bone marrow aspirate was selected if both results were available.
cPresence of ≥1 of del(17p), t(4;14), or t(14;16).
- Of 290 patients who received SoC, 263 (90.7%) received DPd and 27 (9.3%) received DVd.
- As of the clinical cutoff date (August 1, 2025), 29.0% of Tec-Dara and 71.7% of DPd/DVd patients had discontinued study treatment, primarily due to progressive disease (7.4% in Tec-Dara vs 57.9% in DPd/DVd).
- The median duration of treatment was 32.4 months vs 16.1 months for Tec-Dara vs DPd/DVd, respectively.
- The median relative dose intensity of teclistamab was 97.1%, and between 90.0-97.8% for daratumumab across groups.
- Teclistamab dose reduction was reported in 28.5% of patients who received ≥1 dose of teclistamab.
- The median follow-up was 34.5 months (range, 0.03-45.3).
-
Tec-Dara resulted in a significantly lower risk of disease progression or death than DPd/DVd (P<0.001)1
- The P value crossed the prespecified stopping boundary for superiority for the first interim analysis (P=0.0139)1
- Estimated 36-month progression-free survival rate was 83.4% (95% CI, 78.2-87.4) with Tec-Dara versus 29.7% (95% CI, 23.6-36.0) with DPd/DVd (HR, 0.17; 95% CI 0.12-0.23; P<0.001)1
- In subgroup analyses, PFS favored Tec-Dara across all prespecified and clinically relevant subgroups1
Disease progression or death, n/N
- The proportion of patients achieving ≥CR was significantly higher with Tec-Dara versus DPd/DVd (81.8% vs 32.1%), with a risk ratio (post-hoc) of 2.55 (95% CI, 2.14-3.03)1
- A significant difference was also seen with overall response rate (89.0% vs 75.3%), with a risk ratio of 1.18 (95% CI, 1.09-1.27)1
- With both Tec-Dara and DPd/DVd, among responders, the median time to first response was 1.2 months, and to ≥CR, 6.9 months1
- The estimated percentage of patients remaining in response at 36 months was 88.5% (95% CI, 83.7-92.0) versus 36.4% (95% CI, 28.9-43.9) with Tec-Dara and DPd/DVd, respectively1
- MRD negativity was evaluated in the NGS primary analysis set, defined as all randomized patients in the study except those recruited in China, which included 262 patients from the Tec-Dara group and 269 from the DPd/DVd group1
- MRD-negativity rate (10-5) ≥CR was 57.6% in the Tec-Dara group and 17.1% in the DPd/DVd group, with odds ratio of 6.54 (95% CI, 4.37-9.77)4
- MRD-negativity rate (10-6) ≥CR was 53.8% in the Tec-Dara group and 10.4% in the DPd/DVd group, with odds ratio of 9.70 (95% CI, 6.11-15.42)4
- Sustained MRD-negative ≥CR or better was defined as ≥CR achieved and confirmed ≥6 months apart (-1 month) without a positive MRD assessment, progressive disease, or subsequent antimyeloma therapy in between
- Sustained MRD-negative rate (10-5) ≥CR was 46.6% in the Tec-Dara group and 11.2% in the DPd/DVd group, with odds ratio of 6.78 (95% CI, 4.31-10.64)4
- Sustained MRD-negative rate (10-6) ≥CR was 39.3% in the Tec-Dara group and 6.3% in the DPd/DVd group, with odds ratio of 9.20 (95% CI, 5.31-15.95)4
- In the NGS primary analysis set, MRD-negativity rate (10-5) was higher with Tec-Dara versus DPd/DVd (58.4% vs 17.1%) with a risk ratio of 3.43 (95% CI, 2.58-4.55)1
- Tec-Dara demonstrated a significantly lower risk of death than DPd/DVd (stratified log-rank test P<0.0001). Estimated 36-month OS rate was 83.3% (95% CI, 78.3-87.2) with Tec-Dara and 65.0% (95% CI, 58.8-70.5) with DPd/DVd1
- The OS curves crossed around 10 months of follow-up, primarily due to early infectious deaths in the Tec-Dara group1
- Analysis of RMST demonstrated OS benefit for Tec-Dara versus DPd/DVd (RMST difference [Tec-dara minus DPd/DVd], 2.15 months [95% CI, 0.54-3.77])1
- The proportion of patients alive at 6- and 30-months post-treatment were 92.2% and 84.3%, respectively, with Tec-Dara, suggesting a plateau starting around 6 months, and 94.5% and 69.6% with DPd/DVd1
- The most common treatment-emergent adverse events are shown below1,4. Serious adverse events occurred in 70.7% of Tec-Dara patients and 62.4% of DPd/DVd patients, the most common being pneumonia1
aMost common of any Grade were defined as those occurring in ≥30% of patients in either treatment group; most common grade 3/4 TEAEs were defined as those occurring in ≥10% of patients in either treatment group.
- Treatment discontinuation due to TEAEs occurred in 4.6% of patients in the Tec-Dara group and 5.5% of patients in the DPd/DVd group1
- Forty-five (15.9%) Tec-Dara patients and 96 (33.1%) DPd/DVd patients died, mainly due to adverse events and disease progression, respectively1
- There were 20 (7.1%) deaths due to treatment-emergent adverse events in the Tec-Dara group vs 17 (5.9%) in the DPd/DVd group; 12 (4.2%) deaths with Tec-Dara and 5 (1.7%) with DPd/DVd were due to a treatment-emergent adverse event related to study treatment as assessed by investigator1
- CRS occurred in 60.1% of Tec-Dara patients, all of which were grade 1 (44.2%) or grade 2 (15.9%)1
- CRS events were transient, with a median duration of 2 days (range, 1-22 days). All resolved and none led to treatment discontinuation1
- Most events occurred during the step-up dosing schedule; no grade 2 events occurred post-cycle 11
- In the Tec-Dara group, 56.9% of patients received supportive measures to treat CRS and CRS symptoms. Most common supportive measures included but were not limited to paracetamol (42.4%), tocilizumab(29.3%), antibiotics (20.1%), and intravenous fluids (10.2%)1
- ICANS occurred in 3 patients (1.1%) with Tec-Dara (grade 1, n=2; grade 4, n=1). All events resolved, and the grade 4 event led to teclistamab discontinuation1
- Infections were reported in both groups.
- Any grade infections were reported in 96.5% of Tec-Dara and 84.1% of DPd/DVd patients1
- Most common (≥10%) any grade infections in the Tec-Dara group included but were not limited to: COVID-19 (43.8%), upper respiratory tract infection (40.6%), pneumonia (23.0%), nasopharyngitis (21.9%), sinusitis (18.4%) and rhinovirus infection (15.5%).4
- Most common (≥10%) any grade infections in the DPd/DVd group included but were not limited to: COVID-19 (33.4%), upper respiratory tract infection (30.3%), nasopharyngitis (19.7%), pneumonia (18.3%) and influenza (14.8%).4
- Grade 3/4 infections were reported in 54.1% of Tec-Dara and 43.4% of DPd/DVd patients1
- Most common (≥10%) grade 3/4 infections in the Tec-Dara group included but were not limited to: pneumonia (16.6%) and COVID-19 pneumonia (11.3%)4
- Most common (≥10%) grade 3/4 infections in the DPd/DVd group included pneumonia (14.8%)4
- New-onset grade ≥3 infections decreased after 6 months of treatment, coinciding with transition to monthly dosing1
- Incidence of COVID-19 infection (any grade: 43.8% vs. 33.4%; grade 3/4: 6.0% vs. 2.1%; serious: 6.7% vs 2.1%) and COVID-19 pneumonia (any grade: 12.0% vs. 4.1%; grade 3/4: 11.3% vs. 2.4%; serious: 11.3% vs 2.8%), by preferred term, were higher with Tec-Dara than DPd/DVd1
- Fatal infections occurred in 13 patients (4.6%) with Tec-Dara (3 due to COVID-19) and 4 patients (1.4%) with DPd/DVd. Twelve of 13 infection-related deaths on Tec-Dara occurred ≤6 months following treatment initiation, before the implementation of reinforced protocol-specified immunoglobulin replacement; 9 of 12 patients did not receive any immunoglobulin coverage1
- Any grade infections were reported in 96.5% of Tec-Dara and 84.1% of DPd/DVd patients1
- Hypogammaglobulinemia occurred in 239 patients (84.5%) with Tec-Dara and 175 (60.3%) with DPd/DVd; 247 (87.3%) Tec-Dara patients and 130 (44.8%) DPd/DVd patients received ≥1 dose of immunoglobulin treatment1
- Second primary cancer was observed in 35 patients (12.4%) with Tec-Dara and 25 patients (8.6%) with DPd/DVd; most cases were cutaneous or noninvasive (Tec-Dara, 8.1%; DPd/DVd, 4.5%)1
Primary publication
Conflict of interest:
- The MajesTEC-3 study is sponsored by Janssen Research & Development, LLC.
- The authors’ conflict of interest disclosures are as follows: Luciano Costa received research funding from AbbVie, Amgen, Bristol-Myers Squibb, Caribou Biosciences, Genentech, and Janssen Biotech; served a consulting role for AbbVie, Adaptive Biotechnologies, Amgen, Caribou Biosciences, Genentech, Janssen Biotech, Pfizer, and Regeneron Pharmaceuticals; and served on advisory boards for Bristol-Myers Squibb and Sanofi Pasteur. Nizar Bahlis served on advisory boards, clinical trial steering committees, and as a clinical investigator for AbbVie, Amgen Canada, Bristol-Myers Squibb Canada, Celgene, Janssen Biotech, and Karyopharm Therapeutics; served on advisory boards and as a clinical investigator for Genentech USA, Pfizer Canada, Sanofi Pasteur; served as an IRC member for Janssen Biotech; served as an expert witness for Bristol-Myers Squibb Canada; participated in data and safety monitoring for Celgene; received research funding from Pfizer Canada; and received honorarium and research support from Bristol-Myers Squibb and Celgene. Aurore Perrot served as a consultant for AbbVie, Adaptive Biotechnologies, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Biotech, Pfizer, Sanofi, Sanofi US Services, Stemline Therapeutics, and Takeda Oncology; and served on an endpoint review committee for Sanofi. Ajay Nooka served as a consultant for AstraZeneca, Blue Earth Diagnostics, Cellectar, GlaxoSmithKline, Janssen Biotech, Kite Pharma, ONK Therapeutics, OPNA, Perceptive Informatics, Premier Consulting, Sanofi US Services, and Sebia; served on advisory boards for Centro Pfizer-Universidad de Granada-Junta de Andalucía de Genómica e Investigación Oncológica, and Janssen Biotech; participated in data and safety monitoring for Janssen Biotech; and is an employee of Winship Cancer Institute. Charlotte Pawlyn received clinical trial funding paid to their institution from Bristol-Myers Squibb, Janssen Pharmaceuticals, and Pfizer; received travel support from Janssen Pharmaceuticals; served on advisory boards for AbbVie, Bristol-Myers Squibb, Janssen Pharmaceuticals, Menarini Stemline, Opna Bio, Pfizer, and Sanofi; received honoraria from AbbVie, GlaxoSmithKline, Janssen Pharmaceuticals, Pfizer, and Sanofi; served as a consultant for AstraZeneca and iTeos Therapeutics; served as a speaker for Adaptive Biotechnologies and Menarini Stemline; served on a steering committee for Menarini Stemline; and participated in data and safety monitoring for Bristol-Myers Squibb. Roberto Mina served as a speaker for AbbVie, Bristol-Myers Squibb, Janssen Pharmaceuticals, and Sanofi; provided internal training for Amgen and Janssen Pharmaceuticals; served on advisory boards for Bristol-Myers Squibb, GlaxoSmithKline, Janssen Cilag EMEA, Janssen Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals, and Takeda Oncology; and served as a consultant for F. Hoffmann-La Roche, and Janssen Pharmaceuticals. Alain Kentos served on advisory boards for GlaxoSmithKline, Janssen Pharmaceuticals, and Sanofi. Vania Hungria served as a consultant for AbbVie, Amgen, Bristol-Myers Squibb, Celgene, GlaxoSmithKline, Janssen Biotech, Pfizer, Regeneron, Roche, Sanofi and Genzyme US Companies, and Takeda Oncology. Donna Reece participated in data and safety monitoring for Bristol-Myers Squibb; served as clinical trial investigator for Bristol-Myers Squibb, Celgene, Janssen Biotech, and Sanofi; served as an expert witness for Janssen Biotech; served on advisory boards for Janssen Biotech and Sanofi; and served as a speaker for Janssen Biotech, Pfizer, and Sanofi. Rachel Teipel served on advisory boards and/or received honoraria from AbbVie, Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Johnson & Johnson, OncoPep, Pfizer, Sanofi, and Stemline Therapeutics; received travel support from Johnson & Johnson; and received research funding from Johnson & Johnson. Britta Besemer served on an advisory board for GlaxoSmithKline; received honoraria from Janssen Biotech and Pfizer; and received travel support from Amgen and Sanofi. Meletios Dimopoulos received honoraria and served on advisory boards for Amgen, Astra, BeiGene, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Global Services, Menarini Silion Biosystems, Regeneron Pharmaceuticals, Sanofi, Swixx Biopharma, and Takeda Oncology; and received travel support from Amgen, Bristol-Myers Squibb, Janssen Global Services, and Takeda Oncology. Elena Zamagni served a consulting/advisory role for Amgen, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Cilag EMEA, Menarini International, Oncopeptides, Pfizer, Sanofi, and Takeda Pharmaceutical. Satoshi Yoshihara received honorarium from AbbVie, Bristol-Myers Squibb, Genmab, Gilead Sciences, GlaxoSmithKline, Ono Pharmaceuticals, Otsuka Pharmaceuticals, and Sanofi; and served on advisory boards for Johnson & Johnson and Pfizer. Kihyun Kim received research funding from Amgen, Celgene, Janssen Global Services, and Sanofi. Juan Luis Reguera served as a speaker for Amgen, Bristol-Myers Squibb, Janssen Pharmaceuticals, and Kite Pharma; received travel support from Kite Pharma; served as clinical trial investigator for Bristol-Myers Squibb, Janssen Pharmaceuticals, and Kite Pharma; and served on advisory boards for Kite Pharma. Markus Hansson served on advisory boards for Amgen, AstraZeneca, Bristol-Myers Squibb, GlaxoSmithKline, Janssen Cilag EMEA, OncoPep, and Pfizer; and served as an educational lecturer for Sanofi. Mehmet Turgut served as an advisor for AbbVie. Mark Grey received speaker fees from AbbVie, Johnson & Johnson, and Pfizer. Surbhi Sidana served as a consultant for AbbVie, Bristol-Myers Squibb, Genentech, Janssen Biotech, Kite Pharma, Legend Biotech, Magenta Therapeutics, Pfizer, Regeneron Pharmaceuticals, and Sanofi US Services; received research funding from Janssen Biotech and Novartis; and is an employee of Stanford University School of Medicine. Paula Rodriguez Otero served as a consultant for AbbVie, AstraZeneca, F. Hoffmann-La Roche, H3 Biomedicine, Johnson & Johnson, Menarini Stemline España, and Oncopeptides; served on advisory boards for Bristol-Myers Squibb, F. Hoffmann-La Roche, GlaxoSmithKline, Janssen Global Services, Laboratorios Pfizer, and Sanofi Pasteur; served on the speaker bureau for AbbVie, Bristol-Myers Squibb, Janssen Global Services, and Regeneron Pharmaceuticals; served on steering committees for Bristol-Myers Squibb, Janssen Pharmaceuticals, and Regeneron Pharmaceuticals; received honoraria from Sanofi Pasteur; and is an employee of Clinica Universidad de Navarra. Joaquin Martinez-Lopez served on advisory boards for Astellas Pharma, Bristol-Myers Squibb, F. Hoffman-La Roche, Janssen Biotech, Janssen Global Services, Johnson & Johnson, Novartis, and Sanofi Pasteur Biologics; received research funding from Bristol-Myers Squibb; and is an employee of Universidad Complutense de Madrid. Hamza Hashmi served as a consultant for Janssen Biotech and Karyopharm Therapeutics. Robin Carson is an employee of and holds stock options in Johnson & Johnson. Rachel Kobos is an employee of and holds stocks/stock options in Johnson & Johnson. Weili Sun is an employee of Janssen Biotech. Kristen Lantz is an employee of and holds stocks in Johnson & Johnson. Annie Seifert is an employee of and holds stock options in Johnson & Johnson International. Deborah Briseno-Toomey is an employee of Johnson & Johnson. Lisa O’Rourke is an employee of and holds stocks in Johnson & Johnson. Diego Vieyra is an employee of Johnson & Johnson Health Care Systems. Lijuan Kang is an employee of Johnson & Johnson. Maria-Victoria Mateos served as a lecturer for Amgen, Celgene, GlaxoSmithKline, Janssen Global Services, Kite Pharma, Laboratorios Pfizer, Sanofi Pasteur, and Takeda Oncology; served on advisory boards for Celgene, GlaxoSmithKline, Janssen Global Services, Kite Pharma, Laboratorios Pfizer, Oncopeptides, Regeneron Pharmaceuticals, and Sanofi Pasteur; served as a consultant for F. Hoffmann-La Roche, Kite Pharma, and Stemline Therapeutics; and is an employee of University Hospital of Salamanca. No conflict of interest: Jin Lu, Gaston Caeiro, Ting Niu, Anne Mylin, Charlotte Hansen, Changki Min, Paul Geerts, Elena van Leeuwen-Segarceanu, Agata Tyczynksa, Magnus Johansson, Maria Rubin
Additional information can be found in the publication and supplemental material including:
- Patient Disposition
- Representativeness of Study Participants
- Pharmacokinetics and Immunogenicity
- Fatal Infection Incidence in the MajesTEC-3 Study Before and After Implementation of Reinforced IgRT Guidance Overlaid with COVID-19 Pandemic Worldwide Deaths
- Summary of Treatment Cycle Delays, Incidence, and Reason for Study Treatment Dose Modification
- List of All Deaths on Study in the Safety Population
- Summary of Occurrence of CRS by Toxicity Grade in the Safety Population
- Summary of ICANS Events in the Safety Population
- Summary of Treatment-Emergent Grade ≥3 Cytopenic Adverse Events Over Time in the Safety Population
- Summary of Treatment-Emergent Grade ≥3 Infections and Infestations Over Time in the Safety Population
- Summary of Second Primary Malignancies in the Safety Population
- Costa LJ, et al. N Engl J Med. DOI: 10.1056/NEJMoa2514663.
- TECVAYLI® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
- DARZALEX FASPRO® [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
- Costa LJ, et al. N Engl J Med. DOI: 10.1056/NEJMoa2514663. Supplemental Appendix
| AE | Adverse event | NGS | Next generation sequencing |
|---|---|---|---|
| BCMA | B-cell maturation antigen | NE | Not estimable |
| CI | Confidence interval | ORR | Overall response rate |
| COVID-19 | Coronavirus disease 2019 | OS | Overall survival |
| CR | Complete response | PFS | Progression-free survival |
| CRS | Cytokine release syndrome | PR | Partial response |
| Dara | DARZALEX FASPRO® | QW | Weekly |
| DOR | Duration of response | Q2W | Every other week |
| DPd | DARZALEX FASPRO® and hyaluronidase, pomalidomide, and dexamethasone | Q4W | Every 4 weeks |
| DVd | DARZALEX FASPRO® and hyaluronidase, bortezomib, and dexamethasone | REMS | Risk Evaluation and Mitigation Strategy |
| ECOG PS | Eastern Cooperative Oncology Group Performance Status | RMST | Restricted mean survival time |
| FDA | U.S. Food and Drug Administration | RRMM | Relapsed/refractory multiple myeloma |
| HR | Hazard ratio | sCR | Stringent complete response |
| ICANS | Immune effector cell-associated neurotoxicity syndrome | SC | Subcutaneous |
| IRC | Independent Review Committee | SoC | Standard of care |
| IgRT | Immunoglobulin replacement therapy | SUD | Step-up dosing |
| IMWG | International Myeloma Working Group | TEAE | Treatment emergent adverse event |
| LOT | Line of therapy | Tec | Teclistamab |
| MM | Multiple myeloma | TSS | Total Symptom Score |
| MRD | Minimal residual disease | URTI | Upper respiratory tract infection |
| MySIm-Q | Multiple Myeloma Symptom and Impact Questionnaire | VGPR | Very good partial response |