Lenalidomide

More than half of patients maintained minimal residual disease (MRD) negativity (10-5) with DARZALEX FASPRO® for 24 months or longer in the Phase 3 PERSEUS study Data from Phase 3 CEPHEUS study show 60 percent overall MRD negativity (10−5) and improved PFS with DARZALEX FASPRO® in transplant-ineligible newly diagnosed patients CHICAGO, June 3, 2025 /PRNewswire/ -- Johnson & Johnson (NYSE: JNJ) today announced data from two studies highlighting that a DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj)-based quadruplet regimen demonstrated deep and sustained minimal residual disease (MRD) negativity rates, and improved long-term progression-free survival (PFS) in patients with newly diagnosed multiple myeloma (NDMM), regardless of transplant status.1,2,3 Findings were highlighted as oral presentations of an analysis of sustained MRD in transplant-eligible patients from the Phase 3 PERSEUS study (Abstract #7501) and a subgroup analysis of transplant-ineligible patients in the Phase 3 CEPHEUS study (Abstract #7516) at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting. New analysis from the Phase 3 PERSEUS study shows the addition of DARZALEX FASPRO® to bortezomib, lenalidomide and dexamethasone (D-VRd), followed by an investigational maintenance regimen of DARZALEX FASPRO® with lenalidomide (D-R), led to improved and deepened rates of overall and sustained MRD negativity (10-5), defined as no cancer cells detected within 100,000 bone marrow cells) for at least 24 months, compared to VRd induction and consolidation with R maintenance. More than half of patients who received the DARZALEX FASPRO®-based regimen achieved sustained MRD negativity for 24 or more months and more than two-thirds of patients achieved sustained MRD-negativity at 12-months, showing 95.3 percent PFS at 48-months (95 percent confidence interval [CI], 0.3-2.3)—reinforcing the ability of DARZALEX FASPRO® to delay disease progression or death.1 "The data show that D-VRd followed by an investigational D-R maintenance regimen is a highly effective treatment option for transplant-eligible patients with newly diagnosed multiple myeloma," said Philippe Moreau*, M.D., head of the Hematology Department, University Hospital Hôtel-Dieu, Nantes, France and presenting author. "The depth and durability of MRD negativity observed—paired with unprecedented progression-free survival at four years—underscore the long-term benefit the DARZALEX FASPRO-based regimen can offer patients early in their treatment journey." At a median follow-up of 47.5 months, 24-month sustained MRD negativity rates at the 10⁻⁵ sensitivity threshold were more than double with D-VRd followed by investigational D-R maintenance (55.8 percent), compared to VRd followed by R maintenance (22.6 percent) (odds ratio [OR]=4.36; 95 percent CI, 3.15-6.05; P<0.0001). Similarly, MRD negativity at 12 months was higher with D-VRd and D-R maintenance at 64.8 percent compared to VRd and R maintenance (29.7 percent) (OR=4.42, 95 percent CI, 3.22-6.08, P<0.0001).1 Additional data from Phase 3 CEPHEUS study explore the benefits of DARZALEX FASPRO® in transplant-ineligible patients across cytogenetic risk status The post-hoc analysis of the Phase 3 CEPHEUS study focused exclusively on transplant-ineligible patients, reinforcing that adding DARZALEX FASPRO® to VRd significantly deepens response and prolongs PFS compared to VRd alone, even in patients who are older and considered frail by the Myeloma Geriatric Assessment score. At a median follow-up of 58.7 months, patients receiving D-VRd achieved markedly higher overall MRD negativity rates at the 10⁻⁵ sensitivity threshold with 60.4 percent versus 39.3 percent with VRd (OR 2.37; 95 percent CI, 1.47–3.80; P=0.0004). Furthermore, treatment with D-VRd resulted in high MRD-negativity rates at the 10⁻⁶ threshold (no cancer cells detected within 1,000,000 bone marrow cells) with 45.8 percent compared to 26.9 percent with VRd (OR 2.28; 95 percent CI, 1.40–3.73; P=0.0010). These deeper responses translated into improved long-term outcomes, with 69 percent of patients remaining progression free at 54-months when treated with D-VRd versus 48.0 percent with VRd (hazard ratio [HR] 0.51; 95 percent CI, 0.35–0.74). Overall survival (OS) numerically favored D-VRd (HR 0.66; 95 percent CI, 0.42–1.03), with an even greater benefit observed after censoring for COVID-19-related deaths (HR 0.55; 95 percent CI, 0.34–0.90).2 Additional data presented at ASCO included a subgroup analysis of the CEPHEUS trial for both transplant-ineligible and deferred NDMM patients who were considered high-risk for cytogenetic abnormalities (Abstract #7529). At a median follow-up of 58.7 months, overall MRD negativity rate was improved for patients with standard risk in D-VRd versus VRd. Rates by treatment arm in patients at high risk were comparable.3 "Across multiple studies, the growing body of data on DARZALEX-based regimens indicates impressive, deep responses and meaningful progression-free survival in patients with newly diagnosed multiple myeloma, including high risk," Jordan Schecter, MD, Vice President, Disease Area Leader, Multiple Myeloma, Johnson & Johnson Innovative Medicine. "These consistent results across patient populations, regardless of transplant eligibility, reinforce the role of DARZALEX FASPRO as a cornerstone of frontline therapy." In the PERSEUS and CEPHEUS studies, the safety profiles were consistent with the known safety profile for DARZALEX FASPRO®. About the PERSEUS Study The PERSEUS study is being conducted in collaboration with the European Myeloma Network as the sponsor. PERSEUS is an ongoing, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd during induction and consolidation versus VRd during induction and consolidation in patients with NDMM eligible for ASCT. Following consolidation, patients received an investigational treatment regimen for maintenance that included DARZALEX FASPRO® in combination with lenalidomide or lenalidomide alone. The trial was not designed to isolate the effect of DARZALEX FASPRO® in the maintenance phase of treatment. The efficacy of DARZALEX FASPRO® in combination with lenalidomide for maintenance has not been established. The primary endpoint is PFS, and secondary endpoints include overall CR or better rate, and overall MRD-negativity (in patients with CR or better). The median age is 61.0 (range, 32-70) years for patients in the D-VRd arm and 59.0 (range, 31-70) years for patients in the VRd arm.2 The study is being conducted in 14 countries in Europe and Australia. About the CEPHEUS Study CEPHEUS (NCT03652064) is an ongoing, multicenter, randomized, open-label, Phase 3 study comparing the efficacy and safety of D-VRd versus VRd in patients with newly diagnosed multiple myeloma who are transplant-ineligible or for whom transplant is not intended as initial therapy. Primary endpoint is overall MRD negativity rate at 10-5 sensitivity threshold. Secondary endpoints include CR or better rates, PFS, sustained MRD negativity rates for ≥12 months, MRD-negative rate at one year, overall response rates, time to and duration of response, PFS on next line of therapy, overall survival and safety. The trial has enrolled 396 patients in 13 countries. About Multiple Myeloma Multiple myeloma (MM) is a blood cancer that affects a type of white blood cell called plasma cells, which are found in the bone marrow.4 In multiple myeloma, these malignant plasma cells proliferate and replace normal cells in the bone marrow.5 Multiple myeloma is the second most common blood cancer worldwide and remains an incurable disease.6 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma in the U.S. and more than 12,000 will die from the disease.7 People with multiple myeloma have a 5-year survival rate of 59.8 percent. 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, kidney problems or infections.8,9 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 MM, four of which are for frontline treatment in newly diagnosed patients who are transplant-eligible or ineligible.3,6 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® (daratumumab) received U.S. FDA approval in November 2015 and is approved in eight indications, three of which are in the frontline setting, including newly diagnosed patients who are transplant-eligible and ineligible.9 DARZALEX® is the first CD38-directed antibody approved to treat MM.9 DARZALEX®-based regimens have been used in the treatment of more than 618,000 patients worldwide. 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 .  DARZALEX FASPRO ® INDICATIONS AND IMPORTANT SAFETY INFORMATION    INDICATIONS  DARZALEX FASPRO® (daratumumab and hyaluronidase-fihj) is indicated for the treatment of adult patients with MM:  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 MM 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 MM 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 MM (N=1056) or light chain (AL) amyloidosis (N=193) who received DARZALEX FASPRO® as monotherapy or in combination, 7 percent of patients experienced a systemic administration-related reaction (Grade 2: 3.2 percent, Grade 3: 0.7 percent, Grade 4: 0.1 percent). Systemic administration-related reactions occurred in 7 of patients with the first injection, 0.2 percent with the second injection, and cumulatively 1 percent 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 percent) occurred on the day of DARZALEX FASPRO® administration. Delayed systemic administration-related reactions have occurred in 1 percent 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 percent of patients, including Grade 2 reactions in 0.8 percent. The most frequent (>1 percent) 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 MM, the most common adverse reaction (≥20 percent) with DARZALEX FASPRO® monotherapy is upper respiratory tract infection. The most common adverse reactions with combination therapy (≥20 percent 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 percent) 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 ® .     DARZALEX ® INDICATIONS AND IMPORTANT SAFETY INFORMATION INDICATIONS   DARZALEX ® (daratumumab) is indicated for the treatment of adult patients with MM:   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 MM 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 In combination with carfilzomib and dexamethasone in patients with relapsed or refractory MM 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 proteasome inhibitor (PI) and an immunomodulatory agent or who are double-refractory to a PI and an immunomodulatory agent CONTRAINDICATIONS DARZALEX® is contraindicated in patients with a history of severe hypersensitivity (eg, anaphylactic reactions) to daratumumab or any of the components of the formulation.   WARNINGS AND PRECAUTIONS   Infusion-Related Reactions   DARZALEX® can cause severe and/or serious infusion-related reactions including anaphylactic reactions. These reactions can be life-threatening, and fatal outcomes have been reported. In clinical trials (monotherapy and combination: N=2066), infusion-related reactions occurred in 37 percent of patients with the Week 1 (16 mg/kg) infusion, 2 percent with the Week 2 infusion, and cumulatively 6 percent with subsequent infusions. Less than 1 percent of patients had a Grade 3/4 infusion-related reaction at Week 2 or subsequent infusions. The median time to onset was 1.5 hours (range: 0 to 73 hours). Nearly all reactions occurred during infusion or within 4 hours of completing DARZALEX®. Severe reactions have occurred, including bronchospasm, hypoxia, dyspnea, hypertension, tachycardia, headache, laryngeal edema, pulmonary edema, and ocular adverse reactions, including choroidal effusion, acute myopia, and acute angle closure glaucoma. Signs and symptoms may include respiratory symptoms, such as nasal congestion, cough, throat irritation, as well as chills, vomiting, and nausea. Less common signs and symptoms were wheezing, allergic rhinitis, pyrexia, chest discomfort, pruritus, hypotension and blurred vision. When DARZALEX® dosing was interrupted in the setting of ASCT (CASSIOPEIA) for a median of 3.75 months (range: 2.4 to 6.9 months), upon re-initiation of DARZALEX®, the incidence of infusion-related reactions was 11 percent for the first infusion following ASCT. Infusion-related reactions occurring at re-initiation of DARZALEX® following ASCT were consistent in terms of symptoms and severity (Grade 3 or 4: <1 percent) with those reported in previous studies at Week 2 or subsequent infusions. In EQUULEUS, patients receiving combination treatment (n=97) were administered the first 16 mg/kg dose at Week 1 split over two days, ie, 8 mg/kg on Day 1 and Day 2, respectively. The incidence of any grade infusion-related reactions was 42 percent, with 36 percent of patients experiencing infusion-related reactions on Day 1 of Week 1, 4 percent on Day 2 of Week 1, and 8 percent with subsequent infusions. Pre-medicate patients with antihistamines, antipyretics, and corticosteroids. Frequently monitor patients during the entire infusion. Interrupt DARZALEX® infusion for reactions of any severity and institute medical management as needed. Permanently discontinue DARZALEX® therapy if an anaphylactic reaction or life-threatening (Grade 4) reaction occurs and institute appropriate emergency care. For patients with Grade 1, 2, or 3 reactions, reduce the infusion rate when re-starting the infusion. To reduce the risk of delayed infusion-related reactions, administer oral corticosteroids to all patients following DARZALEX® infusions. Patients with a history of chronic obstructive pulmonary disease may require additional post-infusion medications to manage respiratory complications. Consider prescribing short- and long-acting bronchodilators and inhaled corticosteroids for patients with chronic obstructive pulmonary disease. 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 DARZALEX® infusion. If ocular symptoms occur, interrupt DARZALEX® infusion and seek immediate ophthalmologic evaluation prior to restarting DARZALEX®. 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 infusion. 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 is not impacted. Notify blood transfusion centers of this interference with serological testing and inform blood banks that a patient has received DARZALEX®. Type and screen patients prior to starting DARZALEX®. Neutropenia and Thrombocytopenia   DARZALEX® may increase neutropenia and thrombocytopenia 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® until recovery of neutrophils or for recovery of platelets. 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 patients with IgG kappa myeloma protein. Embryo-Fetal Toxicity   Based on the mechanism of action, DARZALEX® can cause fetal harm when administered to a pregnant woman. DARZALEX® 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® and for 3 months after the last dose. The combination of DARZALEX® with lenalidomide, pomalidomide, or thalidomide is contraindicated in pregnant women because lenalidomide, pomalidomide, and thalidomide may cause birth defects and death of the unborn child. Refer to the lenalidomide, pomalidomide, or thalidomide prescribing information on use during pregnancy. ADVERSE REACTIONS   The most frequently reported adverse reactions (incidence ≥20 percent) were: upper respiratory infection, neutropenia, infusion related reactions, thrombocytopenia, diarrhea, constipation, anemia, peripheral sensory neuropathy, fatigue, peripheral edema, nausea, cough, pyrexia, dyspnea, and asthenia. The most common hematologic laboratory abnormalities (≥40 percent) with DARZALEX® are: neutropenia, lymphopenia, thrombocytopenia, leukopenia, and anemia. Please click here to see the full Prescribing Information. 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 or at . Follow us at @JNJInnovMed. Janssen Research & Development, LLC and Janssen Biotech, Inc., and Janssen Global Services, LLC are 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 DARZALEX FASPRO®. 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 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 most recent Annual Report on Form 10-K, 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 , , or on request from Johnson & Johnson. Johnson & Johnson does not undertake to update any forward-looking statement as a result of new information or future events or developments. Source: Johnson & Johnson * Philippe Moreau, M.D., head of the Hematology Department, University Hospital Hôtel-Dieu, Nantes, France, has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. 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Oral presentation of CARTITUDE-1 study data showcases long-term outcomes after a single infusion of CARVYKTI® with one-third of patients with relapsed/refractory multiple myeloma progression-free for ≥5 years CARTITUDE-4 subgroup analyses featured in a poster presentation highlight consistent, durable progression-free and overall survival benefit vs. standard therapies across cytogenetic risk groups as early as second-line therapy Promising early results from ongoing Phase 1 dose-escalation studies of LB1908 in gastroesophageal cancers and LB2102 in lung cancers underscore potential of next-generation cell therapies SOMERSET, N.J. , June 03, 2025 (GLOBE NEWSWIRE) -- Legend Biotech Corporation (NASDAQ: LEGN) ( Legend Biotech ), a global leader in cell therapy, announced today new long-term results from the CARTITUDE-1 study in heavily pretreated relapsed/refractory multiple myeloma (RRMM) patients. RRMM patients were treated with a single infusion of CARVYKTI® (ciltacabtagene autoleucel; cilta-cel) with no maintenance or subsequent myeloma therapy. Notably, an unprecedented 33% (32 of 97) of patients remained progression-free for five years or more. These data were featured in an oral presentation at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #7505). To date, more than 6,500 patients have been treated with CARVYKTI®, the first and only CAR T-cell treatment in multiple myeloma to show overall survival benefit vs. standard of care. In a subset of 12 patients from a single center from this analysis who underwent serial minimal residual disease (MRD) assessments, all 12 patients remained progression-free ≥5 years, were MRD-negative and showed no disease on annual PET/CT scans for five years. “The durability and consistency we’re seeing with CARVYKTI in the CARTITUDE-1 study is truly remarkable,” said Sundar Jagannath , M.D., Network Director, Multiple Myeloma Center of Excellence for Multiple Myeloma at The Tisch Cancer Institute , Icahn School of Medicine at Mount Sinai, New York . “These data offer real hope for long-term disease control in a population that previously had limited options.” ‡ At median follow-up of 61.3 months in CARTITUDE-1 (n=97), patients treated with CARVYKTI® demonstrated a median OS of 60.7 months (95% CI, 41.9–NE). Thirty-two patients (33%) remained progression-free for ≥5 years after a single CARVYKTI® infusion, with no further multiple myeloma treatment. These patients had a median age of 60 years (range, 43-78), received a median of 6.5 prior lines of therapy (range, 3-14), and included patients with high-risk cytogenetics (23.3%), with extramedullary disease (EMD) (12.5%), triple-class refractory disease (90.6%), and penta-drug refractory disease (46.9%). Prior to enrollment, their median time to progression following the last line of therapy was four months. Safety signals were consistent with the known benefit/risk safety profile of CARVYKTI®. No new movement or neurocognitive treatment-emergent adverse events (MNTs)/parkinsonism were reported. Two new cases of second primary malignancies were reported, both solid tumors. These data were also simultaneously published in the Journal of Clinical Oncology . “This five-year survival data highlights the potential of CARVYKTI to fundamentally change treatment expectations for patients with relapsed or refractory multiple myeloma,” said Mythili Koneru , M.D., Ph.D., Chief Medical Officer of Legend Biotech . “For one-third of these heavily pre-treated patients to remain progression-free for five years after a single infusion—and without needing further myeloma therapy—represents a potential paradigm shift in how we treat relapsed or refractory multiple myeloma.” In addition to the long-term survival data, the following updates were provided during poster presentations: CARTITUDE-4: Data from intent-to-treat high-risk subgroups show CARVYKTI® improved progression-free survival (PFS) and overall survival (OS) versus standard therapy (Abstract #7539) CARTITUDE-4 is a Phase 3 study evaluating CARVYKTI® versus two standard of care (SOC) therapies of pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab, pomalidomide, dexamethasone (DPd) in patients with relapsed, lenalidomide-refractory multiple myeloma after one to three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMiD). At median follow-up of 33.6 months, CARVYKTI® demonstrated consistent and durable benefit in PFS and OS compared with SOC across high-risk subgroups, including cytogenetic risk groups, EMD status, and number of prior lines of therapy. In patients with EMD (CARVYKTI®, n=21; standard therapies, n=18): Median PFS was 13 months with CARVYKTI® versus 4 months with standard therapies (HR, 0.71 [95% CI, 0.34–1.49]) Median OS was not reached (NR) with CARVYKTI® versus 16 months with standard therapies (HR, 0.61 [95% CI, 0.26–1.47]) By 1, 2, or 3 prior lines of therapy (pLOT) (CARVYKTI®, n=68, 83, 57; standard therapies, n=68, 87, 56): In patients with one pLOT: Median PFS was NR with CARVYKTI® versus 17 months with standard therapies (HR, 0.41 [95% CI, 0.25–0.67]) Median OS was NR with CARVYKTI® versus NR with standard therapies (HR, 0.56 [95% CI, 0.28–1.11]) In patients with two pLOT: Median PFS was NR with CARVYKTI® versus 12 months with standard therapies (HR, 0.30 [95% CI, 0.19–0.49]) Median OS was NR with CARVYKTI® versus NR with standard therapies (HR, 0.63 [95% CI, 0.36–1.09]) In patients with three pLOT: Median PFS was NR with CARVYKTI® versus 8 months with standard therapies (HR, 0.20 [95% CI, 0.11–0.34]) Median OS was NR with CARVYKTI® versus 34 months with standard therapies (HR, 0.49 [95% CI, 0.26–0.91]) Median PFS was 13 months with CARVYKTI® versus 4 months with standard therapies (HR, 0.71 [95% CI, 0.34–1.49]) Median OS was not reached (NR) with CARVYKTI® versus 16 months with standard therapies (HR, 0.61 [95% CI, 0.26–1.47]) In patients with one pLOT: Median PFS was NR with CARVYKTI® versus 17 months with standard therapies (HR, 0.41 [95% CI, 0.25–0.67]) Median OS was NR with CARVYKTI® versus NR with standard therapies (HR, 0.56 [95% CI, 0.28–1.11]) In patients with two pLOT: Median PFS was NR with CARVYKTI® versus 12 months with standard therapies (HR, 0.30 [95% CI, 0.19–0.49]) Median OS was NR with CARVYKTI® versus NR with standard therapies (HR, 0.63 [95% CI, 0.36–1.09]) In patients with three pLOT: Median PFS was NR with CARVYKTI® versus 8 months with standard therapies (HR, 0.20 [95% CI, 0.11–0.34]) Median OS was NR with CARVYKTI® versus 34 months with standard therapies (HR, 0.49 [95% CI, 0.26–0.91]) Median PFS was NR with CARVYKTI® versus 17 months with standard therapies (HR, 0.41 [95% CI, 0.25–0.67]) Median OS was NR with CARVYKTI® versus NR with standard therapies (HR, 0.56 [95% CI, 0.28–1.11]) Median PFS was NR with CARVYKTI® versus 12 months with standard therapies (HR, 0.30 [95% CI, 0.19–0.49]) Median OS was NR with CARVYKTI® versus NR with standard therapies (HR, 0.63 [95% CI, 0.36–1.09]) Median PFS was NR with CARVYKTI® versus 8 months with standard therapies (HR, 0.20 [95% CI, 0.11–0.34]) Median OS was NR with CARVYKTI® versus 34 months with standard therapies (HR, 0.49 [95% CI, 0.26–0.91]) These data further support a favorable benefit-risk profile for CARVYKTI® as early as after first relapse for multiple myeloma patients who are lenalidomide-refractory and have a poor prognosis. Solid Tumor Pipeline LB1908: Preliminary results of a Phase 1 study of a CLDN18.2-targeted CAR T-cell therapy show manageable safety and antitumor activity in patients with gastroesophageal cancers (Abstract #4022) Interim data from a Phase 1, first-in-human, open-label, multicenter study of LB1908, an autologous CAR-T targeting Claudin 18.2, were presented in patients with advanced gastric, gastroesophageal, and esophageal adenocarcinoma (GC/GEJC/EC) who are relapsed or refractory to one or more prior line of therapy and whose tumors express CLDN18.2 in 50% or more tumor cells. LB1908 demonstrated peripheral expansion and early signs of antitumor activity at the lowest dose tested, with a manageable safety profile. A toxicity mitigation strategy was implemented to address on-target gastric mucosal injury, which successfully reduced toxicity without compromising CAR-T expansion or antitumor activity. Additional data, including longer follow-up and outcomes from patients treated at higher dose levels, were also presented. LB2102: Preliminary results of a Phase 1 study of a DLL3-targeted CAR-T cell therapy demonstrate promising safety and tolerability in patients with lung cancers (Abstract #8104) Interim data from a Phase 1, open-label, multicenter study of LB2102, a DLL3-targeted autologous CAR-T cell therapy armored with dnTGFßRII, were presented in patients with relapsed or refractory small-cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) who have received at least one prior line of therapy. LB2102 was well tolerated, with no dose-limiting toxicities (DLTs) observed through Dose Level 4 (4 x 10⁶ CAR+ T cells/kg). Encouraging signs of dose-dependent efficacy have been observed at higher dose levels, with clinical responses appearing to correlate with CAR-T cell expansion. These preliminary findings support continued dose escalation and further clinical evaluation. In November 2023 , Legend Biotech entered an exclusive, global license agreement with Novartis Pharma AG for certain of our CAR-T cell therapies targeting DLL3, including LB2102. Under the license agreement, Legend Biotech is responsible for conducting the Phase 1 clinical trial for LB2102 in the U.S. Novartis is responsible for conducting all other development for licensed products. “We are proud of the peer recognition for the breadth and depth of our new data in hematologic and solid tumor cancers,” said Ying Huang , Ph.D., Chief Executive Officer of Legend Biotech . "Legend is working to leverage cutting-edge cell therapy modalities to create paradigm-shifting treatments and potential cures for cancer patients." CARVYKTI® IMPORTANT SAFETY INFORMATION WARNINGS AND PRECAUTIONS INCREASED EARLY MORTALITY - In CARTITUDE-4, a (1:1) randomized controlled trial, there was a numerically higher percentage of early deaths in patients randomized to the CARVYKTI® treatment arm compared to the control arm. Among patients with deaths occurring within the first 10 months from randomization, a greater proportion (29/208; 14%) occurred in the CARVYKTI® arm compared to (25/211; 12%) in the control arm. Of the 29 deaths that occurred in the CARVYKTI® arm within the first 10 months of randomization, 10 deaths occurred prior to CARVYKTI® infusion, and 19 deaths occurred after CARVYKTI® infusion. Of the 10 deaths that occurred prior to CARVYKTI® infusion, all occurred due to disease progression, and none occurred due to adverse events. Of the 19 deaths that occurred after CARVYKTI® infusion, 3 occurred due to disease progression, and 16 occurred due to adverse events. The most common adverse events were due to infection (n=12). CYTOKINE RELEASE SYNDROME (CRS), including fatal or life-threatening reactions, occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® for RRMM in the CARTITUDE-1 & 4 studies (N=285), CRS occurred in 84% (238/285), including ≥ Grade 3 CRS (ASCT 2019) in 4% (11/285) of patients. Median time to onset of CRS, any grade, was 7 days (range: 1 to 23 days). CRS resolved in 82% with a median duration of 4 days (range: 1 to 97 days). The most common manifestations of CRS in all patients combined (≥ 10%) included fever (84%), hypotension (29%) and aspartate aminotransferase increased (11%). Serious events that may be associated with CRS include pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia. CRS occurred in 78% of patients in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of patients in CARTITUDE-1 (4% Grade 3 to 4). Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS. Please see Section 5.4; Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS). Ensure that a minimum of two doses of tocilizumab are available prior to infusion of CARVYKTI®. Of the 285 patients who received CARVYKTI® in clinical trials, 53% (150/285) patients received tocilizumab; 35% (100/285) received a single dose, while 18% (50/285) received more than 1 dose of tocilizumab. Overall, 14% (39/285) of patients received at least one dose of corticosteroids for treatment of CRS. Monitor patients at least daily for 10 days following CARVYKTI® infusion at a REMS-certified healthcare facility for signs and symptoms of CRS. Monitor patients for signs or symptoms of CRS for at least 4 weeks after infusion. At the first sign of CRS, immediately institute treatment with supportive care, tocilizumab, or tocilizumab and corticosteroids. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time. NEUROLOGIC TOXICITIES, which may be severe, life-threatening, or fatal, occurred following treatment with CARVYKTI®. Neurologic toxicities included ICANS, neurologic toxicity with signs and symptoms of parkinsonism, GBS, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel patients on the signs and symptoms of these neurologic toxicities, and on the delayed nature of onset of some of these toxicities. Instruct patients to seek immediate medical attention for further assessment and management if signs or symptoms of any of these neurologic toxicities occur at any time. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies for RRMM, one or more neurologic toxicities occurred in 24% (69/285), including ≥ Grade 3 cases in 7% (19/285) of patients. Median time to onset was 10 days (range: 1 to 101) with 63/69 (91%) of cases developing by 30 days. Neurologic toxicities resolved in 72% (50/69) of patients with a median duration to resolution of 23 days (range: 1 to 544). Of patients developing neurotoxicity, 96% (66/69) also developed CRS. Subtypes of neurologic toxicities included ICANS in 13%, peripheral neuropathy in 7%, cranial nerve palsy in 7%, parkinsonism in 3%, and immune mediated myelitis in 0.4% of the patients. Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS): Patients receiving CARVYKTI® may experience fatal or life-threatening ICANS following treatment with CARVYKTI®, including before CRS onset, concurrently with CRS, after CRS resolution, or in the absence of CRS. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, ICANS occurred in 13% (36/285), including Grade ≥3 in 2% (6/285) of the patients. Median time to onset of ICANS was 8 days (range: 1 to 28 days). ICANS resolved in 30 of 36 (83%) of patients with a median time to resolution of 3 days (range: 1 to 143 days). Median duration of ICANS was 6 days (range: 1 to 1229 days) in all patients including those with ongoing neurologic events at the time of death or data cut-off. Of patients with ICANS, 97% (35/36) had CRS. The onset of ICANS occurred during CRS in 69% of patients, before and after the onset of CRS in 14% of patients respectively. Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3) and in 23% of patients in CARTITUDE-1 (3% Grade 3). The most frequent ≥2% manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%), and sleep disorder (2%) [see Adverse Reactions (6.1)]. Monitor patients at least daily for 10 days following CARVYKTI® infusion at the REMS-certified healthcare facility for signs and symptoms of ICANS. Rule out other causes of ICANS symptoms. Monitor patients for signs or symptoms of ICANS for at least 4 weeks after infusion and treat promptly. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed [see Dosage and Administration (2.3)]. Parkinsonism: Neurologic toxicity with parkinsonism has been reported in clinical trials of CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, parkinsonism occurred in 3% (8/285), including Grade ≥ 3 in 2% (5/285) of the patients. Median time to onset of parkinsonism was 56 days (range: 14 to 914 days). Parkinsonism resolved in 1 of 8 (13%) of patients with a median time to resolution of 523 days. Median duration of parkinsonism was 243.5 days (range: 62 to 720 days) in all patients including those with ongoing neurologic events at the time of death or data cut-off. The onset of parkinsonism occurred after CRS for all patients and after ICANS for 6 patients. Parkinsonism occurred in 1% of patients in CARTITUDE-4 (no Grade 3 to 4) and in 6% of patients in CARTITUDE-1 (4% Grade 3 to 4). Manifestations of parkinsonism included movement disorders, cognitive impairment, and personality changes. Monitor patients for signs and symptoms of parkinsonism that may be delayed in onset and managed with supportive care measures. There is limited efficacy information with medications used for the treatment of Parkinson’s disease for the improvement or resolution of parkinsonism symptoms following CARVYKTI® treatment. Guillain-Barré Syndrome: A fatal outcome following GBS occurred following treatment with CARVYKTI® despite treatment with intravenous immunoglobulins. Symptoms reported include those consistent with Miller-Fisher variant of GBS, encephalopathy, motor weakness, speech disturbances, and polyradiculoneuritis. Monitor for GBS. Evaluate patients presenting with peripheral neuropathy for GBS. Consider treatment of GBS with supportive care measures and in conjunction with immunoglobulins and plasma exchange, depending on severity of GBS. Immune Mediated Myelitis: Grade 3 myelitis occurred 25 days following treatment with CARVYKTI® in CARTITUDE-4 in a patient who received CARVYKTI® as subsequent therapy. Symptoms reported included hypoesthesia of the lower extremities and the lower abdomen with impaired sphincter control. Symptoms improved with the use of corticosteroids and intravenous immune globulin. Myelitis was ongoing at the time of death from other cause. Peripheral Neuropathy occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, peripheral neuropathy occurred in 7% (21/285), including Grade ≥3 in 1% (3/285) of the patients. Median time to onset of peripheral neuropathy was 57 days (range: 1 to 914 days). Peripheral neuropathy resolved in 11 of 21 (52%) of patients with a median time to resolution of 58 days (range: 1 to 215 days). Median duration of peripheral neuropathy was 149.5 days (range: 1 to 692 days) in all patients including those with ongoing neurologic events at the time of death or data cut-off. Peripheral neuropathies occurred in 7% of patients in CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of patients in CARTITUDE-1 (2% Grade 3 to 4). Monitor patients for signs and symptoms of peripheral neuropathies. Patients who experience peripheral neuropathy may also experience cranial nerve palsies or GBS. Cranial Nerve Palsies occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, cranial nerve palsies occurred in 7% (19/285), including Grade ≥3 in 1% (1/285) of the patients. Median time to onset of cranial nerve palsies was 21 days (range: 17 to 101 days). Cranial nerve palsies resolved in 17 of 19 (89%) of patients with a median time to resolution of 66 days (range: 1 to 209 days). Median duration of cranial nerve palsies was 70 days (range: 1 to 262 days) in all patients including those with ongoing neurologic events at the time of death or data cut-off. Cranial nerve palsies occurred in 9% of patients in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of patients in CARTITUDE-1 (1% Grade 3 to 4). The most frequent cranial nerve affected was the 7th cranial nerve. Additionally, cranial nerves III, V, and VI have been reported to be affected. Monitor patients for signs and symptoms of cranial nerve palsies. Consider management with systemic corticosteroids, depending on the severity and progression of signs and symptoms. HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)/MACROPHAGE ACTIVATION SYNDROME (MAS): Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, HLH/MAS occurred in 1% (3/285) of patients. All events of HLH/MAS had onset within 99 days of receiving CARVYKTI®, with a median onset of 10 days (range: 8 to 99 days) and all occurred in the setting of ongoing or worsening CRS. The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar damage, coagulopathy and hemorrhage, cytopenia, and multi-organ dysfunction, including renal dysfunction and respiratory failure. Patients who develop HLH/MAS have an increased risk of severe bleeding. Monitor hematologic parameters in patients with HLH/MAS and transfuse per institutional guidelines. Fatal cases of HLH/MAS occurred following treatment with CARVYKTI®. HLH is a life-threatening condition with a high mortality rate if not recognized and treated early. Treatment of HLH/MAS should be administered per institutional standards. CARVYKTI® REMS: Because of the risk of CRS and neurologic toxicities, CARVYKTI® is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the CARVYKTI® REMS. Further information is available at https://www.carvyktirems.com or 1-844-672-0067. PROLONGED AND RECURRENT CYTOPENIAS: Patients may exhibit prolonged and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI® infusion. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, Grade 3 or higher cytopenias not resolved by day 30 following CARVYKTI® infusion occurred in 62% (176/285) of the patients and included thrombocytopenia 33% (94/285), neutropenia 27% (76/285), lymphopenia 24% (67/285) and anemia 2% (6/285). After Day 60 following CARVYKTI® infusion 22%, 20%, 5%, and 6% of patients had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia respectively, after initial recovery of their Grade 3 or 4 cytopenia. Seventy-seven percent (219/285) of patients had one, two, or three or more recurrences of Grade 3 or 4 cytopenias after initial recovery of Grade 3 or 4 cytopenia. Sixteen and 25 patients had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, at the time of death. Monitor blood counts prior to and after CARVYKTI® infusion. Manage cytopenias with growth factors and blood product transfusion support according to local institutional guidelines. INFECTIONS: CARVYKTI® should not be administered to patients with active infection or inflammatory disorders. Severe, life-threatening, or fatal infections, occurred in patients after CARVYKTI® infusion. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, infections occurred in 57% (163/285), including ≥Grade 3 in 24% (69/285) of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 6%, bacterial infections in 5%, and fungal infections in 1% of patients. Overall, 5% (13/285) of patients had Grade 5 infections, 2.5% of which were due to COVID-19. Patients treated with CARVYKTI® had an increased rate of fatal COVID-19 infections compared to the standard therapy arm. Monitor patients for signs and symptoms of infection before and after CARVYKTI® infusion and treat patients appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials according to the standard institutional guidelines. Febrile neutropenia was observed in 5% of patients after CARVYKTI® infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care, as medically indicated. Counsel patients on the importance of prevention measures. Follow institutional guidelines for the vaccination and management of immunocompromised patients with COVID-19. Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients with hypogammaglobulinemia. Perform screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), human immunodeficiency virus (HIV), or any other infectious agents if clinically indicated in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice. HYPOGAMMAGLOBULINEMIA: can occur in patients receiving treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, hypogammaglobulinemia adverse event was reported in 36% (102/285) of patients; laboratory IgG levels fell below 500mg/dl after infusion in 93% (265/285) of patients. Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500mg/dl, after infusion occurred in 94% (267/285) of patients treated. Fifty-six percent (161/285) of patients received intravenous immunoglobulin (IVIG) post CARVYKTI® for either an adverse reaction or prophylaxis. Monitor immunoglobulin levels after treatment with CARVYKTI® and administer IVIG for IgG <400 mg/dL. Manage per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis. Use of Live Vaccines: The safety of immunization with live viral vaccines during or following CARVYKTI® treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during CARVYKTI® treatment, and until immune recovery following treatment with CARVYKTI®. HYPERSENSITIVITY REACTIONS occurred following treatment with CARVYKTI®. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, hypersensitivity reactions occurred in 5% (13/285), all of which were ≤ Grade 2. Manifestations of hypersensitivity reactions included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, non-cardiac chest pain, and pyrexia. Serious hypersensitivity reactions, including anaphylaxis, may be due to the dimethyl sulfoxide (DMSO) in CARVYKTI®. Patients should be carefully monitored for 2 hours after infusion for signs and symptoms of severe reaction. Treat promptly and manage patients appropriately according to the severity of the hypersensitivity reaction. SECONDARY MALIGNANCIES: Patients treated with CARVYKTI® may develop secondary malignancies. Among patients receiving CARVYKTI® in the CARTITUDE-1 & 4 studies, myeloid neoplasms occurred in 5% (13/285) of patients (9 cases of myelodysplastic syndrome, 3 cases of acute myeloid leukemia, and 1 case of myelodysplastic syndrome followed by acute myeloid leukemia). The median time to onset of myeloid neoplasms was 447 days (range: 56 to 870 days) after treatment with CARVYKTI®. Ten of these 13 patients died following the development of myeloid neoplasms; 2 of the 13 cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy. Cases of myelodysplastic syndrome and acute myeloid leukemia have also been reported in the post-marketing setting. T-cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, including CARVYKTI®. Mature T-cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusions and may include fatal outcomes. Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Janssen Biotech, Inc. at 1-800-526-7736 for reporting and to obtain instructions on collection of patient samples. EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: Due to the potential for neurologic events, including altered mental status, seizures, neurocognitive decline, or neuropathy, patients receiving CARVYKTI® are at risk for altered or decreased consciousness or coordination in the 8 weeks following CARVYKTI® infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery during this initial period, and in the event of new onset of any neurologic toxicities.ADVERSE REACTIONS The most common nonlaboratory adverse reactions (incidence greater than 20%) are pyrexia, cytokine release syndrome, hypogammaglobulinemia, hypotension, musculoskeletal pain, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased appetite, upper respiratory tract infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most common Grade 3 or 4 laboratory adverse reactions (incidence greater than or equal to 50%) include lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia. Please read full Prescribing Information, including Boxed Warning, for CARVYKTI®. ABOUT CARVYKTI® (CILTACABTAGENE AUTOLEUCEL; CILTA-CEL) Ciltacabtagene autoleucel is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA. The cilta-cel CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.1 In December 2017, Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen), a Johnson & Johnson company, to develop and commercialize cilta-cel. In February 2022 , cilta-cel was approved by the U.S. Food and Drug Administration (FDA) under the brand name CARVYKTI® for the treatment of adults with relapsed or refractory multiple myeloma. In April 2024 , cilta-cel was approved for the second-line treatment of patients with relapsed/refractory myeloma who have received at least one prior line of therapy including a proteasome inhibitor, an immunomodulatory agent, and are refractory to lenalidomide. In May 2022 , the European Commission (EC) granted conditional marketing authorization of CARVYKTI® for the treatment of adults with relapsed and refractory multiple myeloma. In September 2022 , Japan’s Ministry of Health, Labour and Welfare (MHLW) approved CARVYKTI®. Cilta-cel was granted Breakthrough Therapy Designation in the U.S. in December 2019 and in China in August 2020 . In addition, cilta-cel received a PRIority MEdicines (PRIME) designation from the European Commission in April 2019. Cilta-cel also received Orphan Drug Designation from the U.S. FDA in February 2019 , from the European Commission in February 2020, and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in June 2020. In March 2022 , the European Medicines Agency’s Committee for Orphan Medicinal Products recommended by consensus that the orphan designation for cilta-cel be maintained on the basis of clinical data demonstrating improved and sustained complete response rates following treatment. ABOUT CARTITUDE-1 CARTITUDE-1 (NCT03548207) is a Phase 1b/2, open-label, multicenter study evaluating the safety and efficacy of cilta-cel in adults with relapsed and/or refractory with multiple myeloma who have received at least 3 prior lines of therapy or are double refractory to a PI and IMiD, received a PI, an IMiD, and anti-CD38 antibody and documented disease progression within 12 months of starting the most recent therapy. The primary objective of the Phase 1b portion of the study was to characterize the safety and confirm the recommended Phase 2 dose of cilta-cel, informed by the first-in-human study with LCAR-B38M CAR-T cells (LEGEND-2). The Phase 2 portion further evaluated the efficacy of cilta-cel with overall response rate as the primary endpoint.2 ABOUT CARTITUDE-4 CARTITUDE-4 (NCT04181827) is an ongoing, international, randomized, open-label Phase 3 study evaluating the efficacy and safety of cilta-cel versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in adult patients with relapsed and lenalidomide-refractory multiple myeloma who received one to three prior lines of therapy, including a PI and an IMiD.3 ABOUT LB1908 NCT05539430 is a Phase 1, open label, dose escalation, multicenter study to evaluate Claudin 18.2-targeting CAR-T cells (LB1908) in adult patients with unresectable, locally advanced or metastatic gastric, gastroesophageal junction, esophageal, or pancreatic adenocarcinoma.4 ABOUT LB2102 NCT05680922 is a Phase 1, first-in-human, open-label, multicenter, dose escalation and expansion study of DLL3-targeted chimeric antigen receptor T-cells (LB2102) in patients with extensive stage small cell lung cancer or large cell neuroendocrine lung cancer.5 ABOUT MULTIPLE MYELOMA Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.6 In 2024, it is estimated that more than 35,000 people will be diagnosed with multiple myeloma, and more than 12,000 people will die from the disease in the U.S. 7 While some patients with multiple myeloma initially have no symptoms, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.8 ABOUT GASTRIC, ESOPHAGEAL AND PANCREATIC CANCERS Stomach, esophageal and pancreatic cancers affect the tissue or glands lining these organs. They are often diagnosed when the diseases have progressed to advanced stages. In the U.S., there are an estimated 123,920 people living with stomach cancer and 49,084 living with esophageal cancers.9,10 An estimated 89,248 people in the U.S. live with pancreatic cancer. While all three cancers are treatable, the five-year survival rate is just 32% for gastric cancer; 20% for esophageal cancer; and 11.5% for pancreatic cancer, with definitive treatment at all stages of progression.11,12,13 ABOUT SMALL CELL LUNG CANCER Lung cancer is a leading cause of cancer deaths, contributing to 25 percent of all cancer-related fatalities annually in the United States .14 Small cell lung cancer (SCLC) is the most aggressive, and accounts for roughly 10-15 percent of lung cancer cases in the United States .15,16 An estimated 30,000 to 35,000 people are newly diagnosed with the disease each year.16 This cancer becomes more difficult to treat once it has spread and becomes extensive stage SCLC. Approximately 60 to 70 percent of SCLC patients are diagnosed with metastatic SCLC.15,17 ABOUT LEGEND BIOTECH With over 2,600 employees, Legend Biotech is the largest standalone cell therapy company and a pioneer in treatments that change cancer care forever. The company is at the forefront of the CAR-T cell therapy revolution with CARVYKTI®, a one-time treatment for relapsed or refractory multiple myeloma, which it develops and markets with collaborator Johnson & Johnson. Centered in the US, Legend is building an end-to-end cell therapy company by expanding its leadership to maximize CARVYKTI’s patient access and therapeutic potential. From this platform, the company plans to drive future innovation across its pipeline of cutting-edge cell therapy modalities. Learn more at www.legendbiotech.com and follow us on X (formerly Twitter) and LinkedIn. CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS Statements in this press release about future expectations, plans, and prospects, as well as any other statements regarding matters that are not historical facts, constitute “forward-looking statements” within the meaning of The Private Securities Litigation Reform Act of 1995. These statements include, but are not limited to, statements relating to Legend Biotech’s strategies and objectives; statements relating to CARVYKTI®, including Legend Biotech’s expectations for CARVYKTI® and its therapeutic potential; statements related to the potential results from ongoing studies in the CARTITUDE clinical development program; and the potential benefits of Legend Biotech’s product candidates. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “potential,” “predict,” “project,” “should,” “target,” “will,” “would” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors. Legend Biotech’s expectations could be affected by, among other things, uncertainties involved in the development of new pharmaceutical products; unexpected clinical trial results, including as a result of additional analysis of existing clinical data or unexpected new clinical data; unexpected regulatory actions or delays, including requests for additional safety and/or efficacy data or analysis of data, or government regulation generally; unexpected delays as a result of actions undertaken, or failures to act, by our third party partners; uncertainties arising from challenges to Legend Biotech’s patent or other proprietary intellectual property protection, including the uncertainties involved in the U.S. litigation process; government, industry, and general product pricing and other political pressures; as well as the other factors discussed in the “Risk Factors” section of Legend Biotech’s Annual Report on Form 20-F filed with the Securities and Exchange Commission on March 11, 2025. Should one or more of these risks or uncertainties materialize, or should underlying assumptions prove incorrect, actual results may vary materially from those described in this press release as anticipated, believed, estimated or expected. Any forward-looking statements contained in this press release speak only as of the date of this press release. Legend Biotech specifically disclaims any obligation to update any forward-looking statement, whether as a result of new information, future events or otherwise. ‡ Sundar Jagannath , M.D., Network Director, Multiple Myeloma Center of Excellence for Multiple Myeloma at The Tisch Cancer Institute , Icahn School of Medicine at Mount Sinai, New York , has provided consulting, advisory, and speaking services to Legend Biotech ; has not been paid for any media work. INVESTOR CONTACT: Jessie Yeung Tel: (732) 956-8271 jessie.yeung@legendbiotech.com PRESS CONTACT: MaryAnn Ondish Tel: (914) 552-4625media@legendbiotech.com REFERENCES _____________________ 1 CARVYKTI™ Prescribing Information. Horsham, PA : Janssen Biotech, Inc. 2 ClinicalTrials.gov. A Study of JNJ-68284528, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against B-Cell Maturation Antigen (BCMA) in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1). Available at: https://clinicaltrials.gov/ct2/show/NCT03548207 Accessed October 2022.3 ClinicalTrials.Gov. A Study Comparing JNJ-68284528, a CAR-T Therapy Directed Against B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Participants With Relapsed and Lenalidomide-Refractory Multiple Myeloma (CARTITUDE-4). https://www.clinicaltrials.gov/study/NCT04181827. Accessed March 2024 .4 ClinicalTrials.gov. Claudin 18.2-Targeted Chimeric Antigen Receptor T-cells in Subjects With Unresectable, Locally Advanced, or Metastatic Gastric, Gastroesophageal Junction (GEJ), Esophageal, or Pancreatic Adenocarcinoma. Available at: https://clinicaltrials.gov/study/NCT05539430. Accessed May 20255 ClinicalTrials.gov. DLL3-Directed Chimeric Antigen Receptor T-cells in Subjects With Extensive Stage Small Cell Lung Cancer . Available at: https://www.clinicaltrials.gov/study/NCT05680922. Accessed May 20256 American Cancer Society . ”What is Multiple Myeloma?”. Available at: https://www.cancer.org/cancer/types/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed March 2024 .7 American Cancer Society . “Key Statistics About Multiple Myeloma.” Available at: https://www.cancer.org/cancer/types/multiple-myeloma/about/key-statistics.html. Accessed March 2024 8 American Cancer Society . Multiple myeloma: early detection, diagnosis, and staging. Available at: https://www.cancer.org/content/dam/CRC/PDF/Public/8740.00.pdf. Accessed March 2023 .9 Surveillance, Epidemiology, and End Results (SEER) Program. https://seer.cancer.gov/statfacts/html/stomach.html. Accessed May 2022 .10 Surveillance, Epidemiology, and End Results (SEER) Program. https://seer.cancer.gov/statfacts/html/esoph.html. Accessed May 2022 .11 American Cancer Society . https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.html. Accessed May 2022 .12 American Cancer Society . https://www.cancer.org/cancer/esophagus-cancer/detection-diagnosis-staging/survival-rates.html.Accessed May 2022 .13 Surveillance, Epidemiology, and End Results (SEER) Program. https://seer.cancer.gov/statfacts/html/pancreas.html. Accessed May 2022 .14 American Cancer Society . “Key Statistics for Lung Cancer .” https://www.cancer.org/cancer/lung-cancer/about/key-statistics.html. Accessed November 2022 .15 Byers LA, Rudin CM. Small cell lung cancer: where do we go from here? Cancer. 2015;121(5):664-72.16 Rare Diseases. “Rare Disease Database.” https://rarediseases.org/rare-diseases/small-cell-lung-cancer. Accessed November 2022 .17 Gong J, Salgia R. Managing patients with relapsed small-cell lung cancer. J Oncol Pract. 2018;14(6):359-66. Source: Legend Biotech USA Inc.