TECVAYLI® (teclistamab-cqyv) demonstrates potential as frontline combination therapy for patients with newly diagnosed multiple myeloma

Rhea-AI Summary

Johnson & Johnson (NYSE:JNJ) announced promising frontline data for TECVAYLI® in treating newly diagnosed multiple myeloma (NDMM) from two studies. The MajesTEC-5 study showed 100% MRD negativity in evaluable patients when TECVAYLI® was combined with existing therapies as induction treatment. The MajesTEC-4 study demonstrated TECVAYLI®'s potential as maintenance therapy post-transplant.

In MajesTEC-5, 49 transplant-eligible NDMM patients were treated, with manageable safety profiles. Key adverse events included Grade 1/2 CRS in 65% of patients, and Grade 3/4 events including lymphopenia (43%), neutropenia (57%), and infections (35%). No ICANS cases were reported.

MajesTEC-4 showed promising results with low rates of non-hematologic Grade 3/4 adverse events and treatment discontinuation at 5.3%. All evaluable patients achieved MRD negativity at their respective assessment points.

Positive

• 100% MRD negativity achievement in evaluable patients across both studies
• Low treatment discontinuation rate of 5.3% in MajesTEC-4 study
• No ICANS cases reported in either study
• Manageable safety profiles consistent with individual therapies

Negative

• High rate of Grade 3/4 neutropenia (57%) in MajesTEC-5
• Significant adverse events including lymphopenia (43%) and infections (35%)
• CRS occurred in 65% of patients in MajesTEC-5

Insights

Medical Research Analyst

The MajesTEC-5 and MajesTEC-4 clinical trial results for TECVAYLI® demonstrate remarkable efficacy in newly diagnosed multiple myeloma patients. The 100% MRD negativity rate in both induction and maintenance settings is particularly impressive, as MRD negativity is a strong predictor of improved survival outcomes. The safety profile appears manageable, with mostly Grade 1/2 CRS events and no ICANS observed. The drug's potential in combination with established therapies like DARZALEX FASPRO® could significantly improve frontline treatment options. Most notably, the reduced dosing frequency in cohorts 2 and 3 of MajesTEC-4 showed improved safety profiles with maintained efficacy, suggesting optimal dosing strategies for long-term treatment.

Financial Analyst

This data strengthens J&J's position in the lucrative multiple myeloma market, estimated at $31 billion globally. TECVAYLI®'s potential expansion into frontline therapy represents a significant commercial opportunity, as first-line treatments typically command premium pricing and longer duration of use. The positive safety profile in combination with existing treatments could drive broader adoption and market penetration. Additionally, the maintenance therapy potential could create a sustained revenue stream post-transplant. For context, J&J's DARZALEX® franchise already generates over $8 billion annually and TECVAYLI®'s expansion could further solidify the company's oncology portfolio.

100 percent of evaluable patients for minimal residual disease (MRD) testing achieved MRD negativity in MajesTEC-5 as induction therapy and MajesTEC-4 as maintenance therapy

SAN DIEGO, Dec. 8, 2024 /PRNewswire/ -- Johnson & Johnson (NYSE:JNJ) today announced new frontline data featuring TECVAYLI^® (teclistamab-cqyv) from two investigational studies in patients with newly diagnosed multiple myeloma (NDMM) in induction and maintenance settings. The MajesTEC-5 (Abstract #493) and MajesTEC-4 (Abstract #494) studies establish the potential of TECVAYLI^® for use in newly diagnosed patients, with promising efficacy and a tolerable safety profile. These data were highlighted as oral presentations at the 2024 American Society of Hematology (ASH) Annual Meeting.^1,2

Forty-nine patients with transplant-eligible NDMM were treated with TECVAYLI^® in combination with DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj), lenalidomide and dexamethasone (Tec-DRd) or DARZALEX FASPRO^®, bortezomib, lenalidomide and dexamethasone (Tec-DVRd) as induction therapy in the MajesTEC-5 study.¹ All patients who were evaluated for MRD negativity after cycle 3 of induction therapy achieved MRD negativity (10^-5) and maintained through cycle 6.¹

"These data from the MajesTEC-5 study build on the growing body of evidence of TECVAYLI combinations that support the potential combinability of TECVAYLI with other effective therapies, demonstrating high rates of MRD-negative responses for evaluable patients with newly diagnosed multiple myeloma," said Rachel Kobos, M.D., Vice President, Oncology Research & Development, Johnson & Johnson Innovative Medicine. "At Johnson & Johnson, our deep expertise and understanding of multiple myeloma has shaped the regimens we're developing, including our bispecific antibodies in new combinations, and we're committed to exploring the full potential of our therapies to improve outcomes for patients."

The safety profiles were manageable and consistent with individual safety profiles.¹ No treatment-emergent adverse events (TEAEs) led to study treatment discontinuation or death; cytokine release syndrome (CRS; Grade 1 or 2) occurred in 65 percent of patients.¹ No patients experienced immune effector cell-associated neurotoxicity syndrome (ICANS).¹ Grade 3/4 TEAEs included lymphopenia (43 percent), neutropenia (57 percent) and infections (35 percent).¹ 

"There remains opportunity to achieve even deeper and more sustained outcomes for a broader patient population in the frontline setting," said Marc S. Raab, M.D., Heidelberg University Hospital, Germany.* "These data reinforce the potential of TECVAYLI when used in earlier lines and show that TECVAYLI can be leveraged to optimize existing standard regimens in combination."

Results from the safety run-in of the Phase 3 MajesTEC-4 study highlighted the potential of TECVAYLI^® to be administered as a maintenance therapy following autologous stem cell transplant (ASCT).² MajesTEC-4 is the first study to present data on a B-cell maturation antigen (BCMA) bispecific as monotherapy or combination therapy after ASCT.² 

Low rates of non-hematologic Grade 3/4 TEAEs and discontinuation of treatment due to all TEAEs (5.3 percent) were observed. CRS events were all Grade 1/2, mostly occurring during step-up dosing, and ICANS was not observed. Neutropenia and infections were the most common Grade 3/4 TEAEs.² Grade 3/4 neutropenia at 6 months showed a decreased trend in cohorts 2 and 3 with less frequent TECVAYLI^® dosing (cohort 1: 94 percent, cohort 2: 63 percent, cohort 3: 47 percent).²  A similar trend was observed for all-grade infections (cohort 1: 94 percent; cohort 2: 78 percent; cohort 3: 77 percent).² All evaluable patients in cohort 1 who underwent MRD assessment after 12 months of therapy were MRD negative, and 100 percent of evaluable patients assessed in cohorts 2 and 3 were also MRD negative at cycle 6.²

Further analysis of combination therapies will be evaluated in the Phase 3 MajesTEC-7 study, which is currently enrolling.

About MajesTEC-5 Study
MajesTEC-5 (NCT05695508) is an ongoing, Phase 2 study of teclistamab and talquetamab, evaluating the safety and efficacy of combination regimens in participants with newly diagnosed transplant eligible multiple myeloma.³

About MajesTEC-4 Study
MajesTEC-4 (NCT05243797) is an ongoing, multicenter, randomized, open-label, Phase 3 study of teclistamab in combination with lenalidomide and teclistamab alone versus lenalidomide alone in participants with newly diagnosed multiple myeloma as maintenance therapy following autologous stem cell transplantation.⁴

About MajesTEC-7 Study
MajesTEC-7 (NCT05552222) is a Phase 3 randomized study comparing teclistamab in combination with daratumumab SC and lenalidomide (Tec-DR) and talquetamab in combination with daratumumab SC and lenalidomide (Tal-DR) versus daratumumab SC, lenalidomide, and dexamethasone (DRd) in participants with newly diagnosed multiple myeloma who are either ineligible or not intended for autologous stem cell transplant as initial therapy.⁵

About TECVAYLI^®
TECVAYLI^® (teclistamab-cqyv) received approval from the U.S. FDA in October 2022 as an off-the-shelf (or ready-to-use) antibody that is administered as a subcutaneous treatment for adult patients with relapsed or refractory multiple myeloma (RRMM) who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.⁶ The European Commission (EC) granted TECVAYLI^® conditional marketing authorization (CMA) in August 2022 as monotherapy for the treatment of adult patients with RRMM who have received at least three prior therapies, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody, and have demonstrated disease progression since the last therapy. In August 2023, the EC granted the approval of a Type II variation application for TECVAYLI^®, providing the option for a reduced dosing frequency of 1.5 mg/kg every two weeks in patients who have achieved a complete response (CR) or better for a minimum of six months. TECVAYLI^® is a first-in-class, bispecific T-cell engager antibody therapy that uses innovative science to activate the immune system by binding to the CD3 receptor expressed on the surface of T-cells and to the B-cell maturation antigen (BCMA) expressed on the surface of multiple myeloma cells and some healthy B-lineage cells. In February 2024, the U.S. FDA approved the supplemental Biologics License Application (sBLA) for TECVAYLI^® for a reduced dosing frequency of 1.5 mg/kg every two weeks (Q2W) in patients with relapsed or refractory multiple myeloma who have achieved and maintained a CR or better for a minimum of six months.

For more information, visit www.TECVAYLI.com.

About DARZALEX FASPRO^® and DARZALEX^®
DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj) received U.S. FDA approval in May 2020 and is approved for nine indications in multiple myeloma, four of which are for frontline treatment in newly diagnosed patients who are transplant eligible or ineligible. It is the only subcutaneous CD38-directed antibody approved to treat patients with MM. DARZALEX FASPRO^® is co-formulated with recombinant human hyaluronidase PH20, Halozyme's ENHANZE^® drug delivery technology. 

DARZALEX^® is the first CD38-directed antibody approved to treat multiple myeloma. DARZALEX^®-based regimens have been used in the treatment of more than 585,000 patients worldwide and more than 239,000 patients in the U.S. alone. 

In August 2012, Janssen Biotech, Inc. and Genmab A/S entered a worldwide agreement, which granted Janssen an exclusive license to develop, manufacture and commercialize daratumumab.

For more information, visit https://www.darzalexhcp.com.

About Multiple Myeloma
Multiple myeloma is an incurable blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.⁷ In multiple myeloma, these plasma cells proliferate and spread rapidly and replace normal cells in the bone marrow with tumors.⁸ Multiple myeloma is the third most common blood cancer worldwide and remains an incurable disease.⁹ In 2024, it was estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 people would die from the disease.¹⁰ People living with multiple myeloma have a 5-year survival rate of 59.8 percent.¹¹ While some people diagnosed with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone fracture or pain, low red blood cell counts, tiredness, high calcium levels and kidney problems or infections.^12,13 

TECVAYLI^® IMPORTANT SAFETY INFORMATION 

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL- ASSOCIATED NEUROTOXICITY SYNDROME Cytokine release syndrome (CRS), including life-threatening or fatal reactions, can occur in patients receiving TECVAYLI®. Initiate treatment with TECVAYLI® step-up dosing schedule to reduce risk of CRS. Withhold TECVAYLI® until CRS resolves or permanently discontinue based on severity. Neurologic toxicity, including Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS) and serious and life- threatening reactions, can occur in patients receiving TECVAYLI®. Monitor patients for signs or symptoms of neurologic toxicity, including ICANS, during treatment. Withhold TECVAYLI® until neurologic toxicity resolves or permanently discontinue based on severity. TECVAYLI® is available only through a restricted program called the TECVAYLI® and TALVEY® Risk Evaluation and Mitigation Strategy (REMS).

INDICATION AND USAGE

TECVAYLI^® (teclistamab-cqyv) 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 confirmatory trial(s).

WARNINGS AND PRECAUTIONS

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^® accordingly. 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 or life-threatening 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 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.

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 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.

Please read full Prescribing Information, including Boxed WARNING, for TECVAYLI^®. 

DARZALEX FASPRO^® INDICATIONS AND IMPORTANT SAFETY INFORMATION  

INDICATIONS
DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj) is 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
• In combination with bortezomib, melphalan, and prednisone in newly diagnosed patients who are ineligible for autologous stem cell transplant
• 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
• In combination with bortezomib, thalidomide, and dexamethasone in newly diagnosed patients who are eligible for autologous stem cell transplant
• In combination with pomalidomide and dexamethasone in patients who have received at least one prior line of therapy including lenalidomide and a proteasome inhibitor (PI)
• In combination with carfilzomib and dexamethasone in patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy
• In combination with bortezomib and dexamethasone in patients who have received at least one prior therapy
• As monotherapy in patients who have received at least three prior lines of therapy including a PI and an immunomodulatory agent or who are double refractory to a PI and an immunomodulatory agent

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS 
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 PRECAUTIONS   

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 1249 patients with multiple myeloma (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO^® as monotherapy or in combination, 7% of patients experienced a systemic administration-related reaction (Grade 2: 3.2%, Grade 3: 0.7%, Grade 4: 0.1%). Systemic administration-related reactions occurred in 7% of patients with the first injection, 0.2% with the second injection, and cumulatively 1% with subsequent injections. The median time to onset was 2.9 hours (range: 5 minutes to 3.5 days). Of the 165 systemic administration-related reactions that occurred in 93 patients, 144 (87%) occurred on the day of DARZALEX FASPRO^® administration. Delayed systemic administration-related reactions have occurred in 1% of the patients.

Severe reactions included hypoxia, dyspnea, hypertension, 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, injection-site reactions occurred in 7% of patients, including Grade 2 reactions in 0.8%. The most frequent (>1%) injection-site reaction was injection-site erythema. These local reactions occurred a median of 5 minutes (range: 0 minutes to 6.5 days) after starting administration of DARZALEX FASPRO^®. Monitor for local reactions and consider symptomatic management.   

Neutropenia  
Daratumumab 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  
Daratumumab 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 red blood cells (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 immunoglobulin G (IgG) kappa monoclonal antibody that can be detected on both the serum protein electrophoresis (SPE) and immunofixation (IFE) 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, pyrexia, cough, muscle spasms, back pain, vomiting, hypertension, upper respiratory tract infection, peripheral sensory neuropathy, constipation, pneumonia, and peripheral edema.   

The most common hematology laboratory abnormalities (≥40%) with DARZALEX FASPRO^® are decreased leukocytes, decreased lymphocytes, decreased neutrophils, decreased platelets, and decreased hemoglobin.   

Please click here to see the full Prescribing Information for DARZALEX FASPRO^®. 

About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.

Learn more at https://www.jnj.com/ or at www.innovativemedicine.jnj.com.

Follow us at @JanssenUS and @JNJInnovMed. 

Janssen Research & Development, LLC and Janssen Biotech, Inc. are both Johnson & Johnson companies.

Cautions Concerning Forward-Looking Statements

This press release contains "forward-looking statements" as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of TECVAYLI^® (teclistamab-cqyv) and DARZALEX FASPRO^® (daratumumab and hyaluronidase-fihj). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson's Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned "Cautionary Note Regarding Forward-Looking Statements" and "Item 1A. Risk Factors," and in Johnson & Johnson's subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc. nor Johnson & Johnson undertake to update any forward-looking statement as a result of new information or future events or developments.

^* Marc S. Raab, M.D., has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work.

---

¹Raab, Marc, S., et al, 493 Phase 2 Study of Teclistamab-Based Induction Regimens in Patients with Transplant-Eligible (TE) Newly Diagnosed Multiple Myeloma (NDMM): Results from the GMMG-HD10/DSMM-XX (MajesTEC-5) Trial. 2024 American Society of Hematology Annual Meeting. December 2024.
² Zamagni, Elena, et al., 494 Phase 3 Study of Teclistamab (Tec) in Combination with Lenalidomide (Len) and Tec Alone Versus Len Alone in Newly Diagnosed Multiple Myeloma (NDMM) As Maintenance Therapy Following Autologous Stem Cell Transplantation (ASCT): Safety Run-in (SRI) Results from the MajesTEC-4/EMN30 Trial. 2024 American Society of Hematology Annual Meeting. December 2024.
³ GMMG-HD10 / DSMM-XX / 64007957MMY2003, MajesTEC-5 (HD10/DSMMXX). https://clinicaltrials.gov/study/NCT05695508. Accessed November 2024.
⁴ Phase 3 Study of Teclistamab in Combination With Lenalidomide and Teclistamab Alone Versus Lenalidomide Alone in Participants With Newly Diagnosed Multiple Myeloma as Maintenance Therapy Following Autologous Stem Cell Transplantation (MajesTEC-4). https://clinicaltrials.gov/study/NCT05243797. Accessed November 2024.
⁵ A Study of Teclistamab in Combination With Daratumumab and Lenalidomide (Tec-DR) and Talquetamab in Combination With Daratumumab and Lenalidomide (Tal-DR) in Participants With Newly Diagnosed Multiple Myeloma (MajesTEC-7). https://classic.clinicaltrials.gov/ct2/show/NCT05552222. Accessed November 2024.
⁶ U.S. FDA Approves TECVAYLI^® (teclistamab-cqyv), the First Bispecific T-cell Engager Antibody for the Treatment of Patients with Relapsed or Refractory Multiple Myeloma. https://www.jnj.com/u-s-fda-approves-tecvayli-teclistamab-cqyv-the-first-bispecific-t-cell-engager-antibody-for-the-treatment-of-patients-with-relapsed-or-refractory-multiple-myeloma. Accessed November 2024.
⁷ Rajkumar SV. Multiple myeloma: 2020 update on diagnosis, risk-stratification and management. Am J Hematol. 2020;95(5):548-5672020;95(5):548-567. http://www.ncbi.nlm.nih.gov/pubmed/32212178 ⁸ National Cancer Institute. Plasma Cell Neoplasms. https://www.cancer.gov/types/myeloma/patient/myeloma-treatment-pdq. Accessed November 2024.
⁹ City of Hope. Multiple Myeloma: Causes, Symptoms & Treatments. https://www.cancercenter.com/cancer-types/multiple-myeloma. Accessed November 2024.
¹⁰American Cancer Society. Key Statistics About Multiple Myeloma. https://www.cancer.org/cancer/multiple-myeloma/about/key-statistics.html#:~:text=Multiple%20myeloma%20is%20a%20relatively,men%20and%2015%2C370%20in%20women. Accessed November 2024.
¹¹SEER Explorer: An interactive website for SEER cancer statistics [Internet]. Surveillance Research Program, National Cancer Institute. https://seer.cancer.gov/explorer/. Accessed November 2024.
¹² American Cancer Society. What is Multiple Myeloma? https://www.cancer.org/cancer/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed November 2024.
¹³  American Cancer Society. Multiple Myeloma Early Detection, Diagnosis, and Staging. https://www.cancer.org/cancer/types/multiple-myeloma/detection-diagnosis-staging/detection.html. Accessed November 2024.

 

Media contacts:  Sarah Freeman sfreem21@its.jnj.com   Christie Corbett ccorbet6@its.jnj.com

Investor contact:  Lauren Johnson investor-relations@its.jnj.com     U.S. Medical Inquiries   +1 800 526-7736

 

View original content to download multimedia:https://www.prnewswire.com/news-releases/tecvayli-teclistamab-cqyv-demonstrates-potential-as-frontline-combination-therapy-for-patients-with-newly-diagnosed-multiple-myeloma-302325575.html

SOURCE Johnson & Johnson

FAQ

What were the key results of TECVAYLI in the MajesTEC-5 trial for JNJ?

In the MajesTEC-5 trial, 100% of evaluable patients achieved MRD negativity after cycle 3 of induction therapy and maintained it through cycle 6, with manageable safety profiles.

What is the safety profile of TECVAYLI in the 2024 MajesTEC studies for JNJ?

The safety profile showed Grade 1/2 CRS in 65% of patients, Grade 3/4 events including lymphopenia (43%), neutropenia (57%), and infections (35%), with no ICANS cases and no treatment-related deaths.

What was the treatment discontinuation rate in JNJ's MajesTEC-4 TECVAYLI study?

The MajesTEC-4 study showed a low treatment discontinuation rate of 5.3% due to adverse events.