New knowledge will showcase considerably elevated and sustained minimal residual illness (MRD) negativity charges, reinforcing the potential of CARVYKTI to remodel outcomes in refractory a number of myeloma
MRD knowledge to be featured in oral presentation on the 66th Annual American Society of Hematology (ASH) Annual Assembly
SOMERSET, N.J., Nov. 05, 2024 (GLOBE NEWSWIRE) — Legend Biotech Company (NASDAQ: LEGN) (Legend Biotech), a world chief in cell remedy, will current new knowledge on minimal residual illness (MRD) negativity charges from the Part 3 CARTITUDE-4 trial in a number of myeloma sufferers handled with CARVYKTI ® (ciltacabtagene autoleucel; cilta-cel) versus commonplace of care (SoC). The research evaluated lenalidomide-refractory sufferers who’ve obtained one to a few prior traces of remedy and will probably be featured in an oral presentation on Monday (NASDAQ:), December 9, 2024, at 5:45 p.m. PT on the 66th Annual American Society of Hematology (ASH) Annual Assembly in San Diego.
This 12 months’s ASH knowledge continues to spotlight our advances throughout key medical areas aimed toward serving to healthcare professionals determine the optimum therapy regimens for his or her sufferers with a number of myeloma, mentioned Ying Huang, Ph. D., Chief Govt Officer of Legend Biotech. MRD negativity is a prognostic marker of extended survival outcomes for sufferers with a number of myeloma. The considerably elevated total and sustained MRD negativity charges reinforce CARVYKTI as a transformative therapeutic choice versus the usual of take care of a number of myeloma sufferers as early because the second line.
Information from CARTITUDE-4 supported the U.S. Meals and Drug Administration (FDA) and European Fee (EC) approval of CARVYKTI ® earlier this 12 months for the therapy of grownup sufferers with relapsed or refractory a number of myeloma who’ve obtained a minimum of one prior line of remedy (LOT), together with a proteasome inhibitor (PI), and an immunomodulatory agent (IMiD), and are refractory to lenalidomide.1 CARVYKTI ® is the primary and solely BCMA-targeted CAR-T cell remedy permitted for the therapy of sufferers with a number of myeloma who’ve had a minimum of one prior line of remedy. Globally, CARVYKTI is now commercially accessible in 5 nations and has been utilized by over 4,000 sufferers.
ASH Displays (December 7-10, 2024)
| Summary Title | Authors | Session Particulars |
| Ciltacabtagene Autoleucel (Cilta-cel) vs Normal of Care (SoC) in Sufferers with Lenalidomide-Refractory A number of Myeloma (MM) After 1“3 Traces of Remedy: Minimal Residual Illness (MRD) Negativity within the Part 3 CARTITUDE-4 Trial | Rakesh Popat, Albert Oriol, Michele Cavo, Lionel Karlin, Irit Avivi, Wilfried Roeloffzen, Seok Jin Kim, Brea Lipe, Noffar Bar, Noemi Horvath, Andrew Spencer, Chang Ki Min, Diana Chen, Quanlin Li, Katherine Li, Ana Slaughter, Carolina Lonardi, Nina Benachour, Arnab Ghosh, Martin Vogel, Nikoletta Lendvai, Tamar Lengil, Nitin Patel, Octavio Costa Filho, Erika Florendo, Yi Lin | ORAL 1032 Session Title: 655. A number of Myeloma: Mobile Therapies: Unleashing Cell Therapies Towards Myeloma Session Date: Monday, December 9, 2024 Session Time: 4:30 p.m. – 6:00 p.m. PT Presentation Time: 5:45 – 6:00 p.m. PT Room: Marriott Marquis San Diego Marina, Pacific Ballroom Salons 24-26 |
| Lengthy-Time period Advantages in Affected person-Reported Outcomes and Time to Subsequent (LON:) Anti-Myeloma Remedy of Ciltacabtagene autoleucel (Cilta-cel) Versus Normal of Look after Sufferers With Lenalidomide-Refractory A number of Myeloma: Outcomes From the Part 3 CARTITUDE-4 Scientific Trial | Noffar Bar, Roberto Mina, Anne Ok. Mylin, Hisayuki Yokoyama, Hila Magen, Winfried Alsdorf, Monique C. Minnema, Leyla Shune, Iris Isufi, Simon J. Harrison, Urvi A. Shah, Andr̩ De Champlain, Katherine S. Gries, Diana Chen, Quanlin Li, Tzu-Min Yeh, Ana Slaughter, Carolina Lonardi, Nina Benachour, Arnab Ghosh, William Deraedt, Martin Vogel, Nikoletta Lendvai, Nitin Patel, Octavio Costa Filho, Erika Florendo, Lionel Karlin, Katja Weisel | POSTER 2002 Session Title: 655. A number of Myeloma: Mobile Therapies: Poster I Session Date: Saturday, December 7, 2024 Presentation Time: 6:00 p.m. Р8:00 p.m. PT Room: San Diego Conference Middle, Halls G-H |
| Up to date Comparative Efficacy of Ciltacabtagene Autoleucel Versus Idecabtagene Vicleucel in Sufferers With Relapsed or Refractory A number of Myeloma Beforehand Handled With 2“4 Prior Traces of Remedy Utilizing a Matching-Adjusted Oblique Comparability | Nieves Lopez-Muñoz, Noffar Bar, Joris Diels, Suzy Van Sanden, João Mendes, Seina Lee, Teresa Hernando, Nikoletta Lendvai, Nitin Patel, Tadao Ishida,¯Jeremy Er, Simon J. Harrison, Urvi Shah | POSTER 3390 Session Title: 655. A number of Myeloma: Mobile Therapies: Poster II Session Date: Sunday, December 8, 2024 Presentation Time: 6:00 p.m. – 8:00 p.m. PT Room: San Diego Conference Middle, Halls G-H |
| Efficacy of CARVYKTI in CARTITUDE-4 Versus Different Typical Therapy Regimens for Lenalidomide-Refractory A number of Myeloma Sufferers Utilizing Inverse Chance of Therapy Weighting | Rafael Fonseca, Joris Diels, Francesca Ghilotti, Jọo Mendes, Teresa Hernando, Seina Lee, Jordan M. Schecter, Nikoletta Lendvai, Nitin Patel, Ana Triguero, Winfried Alsdorf, Margherita Ursi | POSTER 2005 Session Title: 655. A number of Myeloma: Mobile Therapies: Poster I Session Date: Saturday, December 7, 2024 Presentation Time: 5:30 p.m. Р7:30 p.m. PT Room: San Diego Conference Middle, Halls G-H |
CARVYKTI ® IMPORTANT SAFETY INFORMATION
| WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED and RECURRENT CYTOPENIA, and SECONDARY HEMATOLOGICAL MALIGNANCIES |
| Cytokine Launch Syndrome (CRS), together with deadly or life-threatening reactions, occurred in sufferers following therapy with CARVYKTI ®. Don’t administer CARVYKTI ® to sufferers with lively an infection or inflammatory problems. Deal with extreme or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Immune Effector Cell-Related Neurotoxicity Syndrome (ICANS), which can be deadly or life-threatening, occurred following therapy with CARVYKTI ®, together with earlier than CRS onset, concurrently with CRS, after CRS decision, or within the absence of CRS. Monitor for neurologic occasions after therapy with CARVYKTI ®. Present supportive care and/or corticosteroids as wanted. Parkinsonism and Guillain-Barré syndrome (GBS) and their related problems leading to deadly or life-threatening reactions have occurred following therapy with CARVYKTI ®. Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS), together with deadly and life-threatening reactions, occurred in sufferers following therapy with CARVYKTI ®. HLH/MAS can happen with CRS or neurologic toxicities. Extended and/or recurrent cytopenias with bleeding and an infection and requirement for stem cell transplantation for hematopoietic restoration occurred following therapy with CARVYKTI ®. Secondary hematological malignancies, together with myelodysplastic syndrome and acute myeloid leukemia, have occurred in sufferers following therapy with CARVYKTI ®. T-cell malignancies have occurred following therapy of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, together with CARVYKTI ®. CARVYKTI ® is obtainable solely by a restricted program beneath a Threat Analysis and Mitigation Technique (REMS) referred to as the CARVYKTI ® REMS Program. |
WARNINGS AND PRECAUTIONS
INCREASED EARLY MORTALITY – In CARTITUDE-4, a (1:1) randomized managed trial, there was a numerically increased proportion of early deaths in sufferers randomized to the CARVYKTI ® therapy arm in comparison with the management arm. Amongst sufferers with deaths occurring throughout the first 10 months from randomization, a higher proportion (29/208; 14%) occurred within the CARVYKTI ® arm in comparison with (25/211; 12%) within the management arm. Of the 29 deaths that occurred within the CARVYKTI ® arm throughout the first 10 months of randomization, 10 deaths occurred previous to CARVYKTI ® infusion, and 19 deaths occurred after CARVYKTI ® infusion. Of the ten deaths that occurred previous to CARVYKTI ® infusion, all occurred as a consequence of illness development, and none occurred as a consequence of antagonistic occasions. Of the 19 deaths that occurred after CARVYKTI ® infusion, 3 occurred as a consequence of illness development, and 16 occurred as a consequence of antagonistic occasions. The most typical antagonistic occasions had been as a consequence of an infection (n=12).
CYTOKINE RELEASE SYNDROME (CRS), together with deadly or life-threatening reactions, occurred following therapy with CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® for RRMM within the CARTITUDE-1 & 4 research (N=285), CRS occurred in 84% (238/285), together with ‰¥ Grade 3 CRS (ASCT 2019) in 4% (11/285) of sufferers. Median time to onset of CRS, any grade, was 7 days (vary: 1 to 23 days). CRS resolved in 82% with a median period of 4 days (vary: 1 to 97 days). The most typical manifestations of CRS in all sufferers mixed ( ‰¥ 10%) included fever (84%), hypotension (29%) and aspartate aminotransferase elevated (11%). Severe occasions that could be related to CRS embrace pyrexia, hemophagocytic lymphohistiocytosis, respiratory failure, disseminated intravascular coagulation, capillary leak syndrome, and supraventricular and ventricular tachycardia. CRS occurred in 78% of sufferers in CARTITUDE-4 (3% Grade 3 to 4) and in 95% of sufferers in CARTITUDE-1 (4% Grade 3 to 4). Determine CRS based mostly on medical presentation. Consider for and deal with different causes of fever, hypoxia, and hypotension. CRS has been reported to be related to findings of HLH/MAS, and the physiology of the syndromes might overlap. HLH/MAS is a doubtlessly life-threatening situation. In sufferers with progressive signs of CRS or refractory CRS regardless of therapy, consider for proof of HLH/MAS. Please see Part 5.4; Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS).
Make sure that a minimal of two doses of tocilizumab can be found previous to infusion of CARVYKTI ®.
Of the 285 sufferers who obtained CARVYKTI ® in medical trials, 53% (150/285) sufferers obtained tocilizumab; 35% (100/285) obtained a single dose, whereas 18% (50/285) obtained greater than 1 dose of tocilizumab. Total, 14% (39/285) of sufferers obtained a minimum of one dose of corticosteroids for therapy of CRS.
Monitor sufferers a minimum of day by day for 10 days following CARVYKTI ® infusion at a REMS-certified healthcare facility for indicators and signs of CRS. Monitor sufferers for indicators or signs of CRS for a minimum of 4 weeks after infusion. On the first signal of CRS, instantly institute therapy with supportive care, tocilizumab, or tocilizumab and corticosteroids.
Counsel sufferers to hunt quick medical consideration ought to indicators or signs of CRS happen at any time.
NEUROLOGIC TOXICITIES, which can be extreme, life-threatening, or deadly, occurred following therapy with CARVYKTI ®. Neurologic toxicities included ICANS, neurologic toxicity with indicators and signs of parkinsonism, GBS, immune mediated myelitis, peripheral neuropathies, and cranial nerve palsies. Counsel sufferers on the indicators and signs of those neurologic toxicities, and on the delayed nature of onset of a few of these toxicities. Instruct sufferers to hunt quick medical consideration for additional evaluation and administration if indicators or signs of any of those neurologic toxicities happen at any time.
Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research for RRMM, a number of neurologic toxicities occurred in 24% (69/285), together with ‰¥ Grade 3 circumstances in 7% (19/285) of sufferers. Median time to onset was 10 days (vary: 1 to 101) with 63/69 (91%) of circumstances growing by 30 days. Neurologic toxicities resolved in 72% (50/69) of sufferers with a median period to decision of 23 days (vary: 1 to 544). Of sufferers growing neurotoxicity, 96% (66/69) additionally 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 sufferers.
Immune Effector Cell-Related Neurotoxicity Syndrome (ICANS): Sufferers receiving CARVYKTI ® might expertise deadly or life-threatening ICANS following therapy with CARVYKTI ®, together with earlier than CRS onset, concurrently with CRS, after CRS decision, or within the absence of CRS.
Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, ICANS occurred in 13% (36/285), together with Grade ‰¥3 in 2% (6/285) of the sufferers. Median time to onset of ICANS was 8 days (vary: 1 to twenty-eight days). ICANS resolved in 30 of 36 (83%) of sufferers with a median time to decision of three days (vary: 1 to 143 days). Median period of ICANS was 6 days (vary: 1 to 1229 days) in all sufferers together with these with ongoing neurologic occasions on the time of dying or knowledge cut-off. Of sufferers with ICANS, 97% (35/36) had CRS. The onset of ICANS occurred throughout CRS in 69% of sufferers, earlier than and after the onset of CRS in 14% of sufferers respectively.
Immune Effector Cell-associated Neurotoxicity Syndrome (ICANS) occurred in 7% of sufferers in CARTITUDE-4 (0.5% Grade 3) and in 23% of sufferers in CARTITUDE-1 (3% Grade 3). Essentially the most frequent ‰¥2% manifestations of ICANS included encephalopathy (12%), aphasia (4%), headache (3%), motor dysfunction (3%), ataxia (2%), and sleep problem (2%) [see Adverse Reactions (6.1)].
Monitor sufferers a minimum of day by day for 10 days following CARVYKTI ® infusion on the REMS-certified healthcare facility for indicators and signs of ICANS. Rule out different causes of ICANS signs. Monitor sufferers for indicators or signs of ICANS for a minimum of 4 weeks after infusion and deal with promptly. Neurologic toxicity needs to be managed with supportive care and/or corticosteroids as wanted [see Dosage and Administration (2.3)].
Parkinsonism: Neurologic toxicity with parkinsonism has been reported in medical trials of CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, parkinsonism occurred in 3% (8/285), together with Grade ‰¥ 3 in 2% (5/285) of the sufferers. Median time to onset of parkinsonism was 56 days (vary: 14 to 914 days). Parkinsonism resolved in 1 of 8 (13%) of sufferers with a median time to decision of 523 days. Median period of parkinsonism was 243.5 days (vary: 62 to 720 days) in all sufferers together with these with ongoing neurologic occasions on the time of dying or knowledge cut-off. The onset of parkinsonism occurred after CRS for all sufferers and after ICANS for six sufferers.
Parkinsonism occurred in 1% of sufferers in CARTITUDE-4 (no Grade 3 to 4) and in 6% of sufferers in CARTITUDE-1 (4% Grade 3 to 4).
Manifestations of parkinsonism included motion problems, cognitive impairment, and persona adjustments. Monitor sufferers for indicators and signs of parkinsonism that could be delayed in onset and managed with supportive care measures. There’s restricted efficacy data with drugs used for the therapy of Parkinson’s illness for the development or decision of parkinsonism signs following CARVYKTI ® therapy.
Guillain-Barré Syndrome: A deadly final result following GBS occurred following therapy with CARVYKTI ® regardless of therapy with intravenous immunoglobulins. Signs reported embrace these per Miller-Fisher variant of GBS, encephalopathy, motor weak point, speech disturbances, and polyradiculoneuritis.
Monitor for GBS. Consider sufferers presenting with peripheral neuropathy for GBS. Take into account therapy of GBS with supportive care measures and along with immunoglobulins and plasma alternate, relying on severity of GBS.
Immune Mediated Myelitis: Grade 3 myelitis occurred 25 days following therapy with CARVYKTI ® in CARTITUDE-4 in a affected person who obtained CARVYKTI ® as subsequent remedy. Signs reported included hypoesthesia of the decrease extremities and the decrease stomach with impaired sphincter management. Signs improved with using corticosteroids and intravenous immune globulin. Myelitis was ongoing on the time of dying from different trigger.
Peripheral Neuropathy occurred following therapy with CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, peripheral neuropathy occurred in 7% (21/285), together with Grade ‰¥3 in 1% (3/285) of the sufferers. Median time to onset of peripheral neuropathy was 57 days (vary: 1 to 914 days). Peripheral neuropathy resolved in 11 of 21 (52%) of sufferers with a median time to decision of 58 days (vary: 1 to 215 days). Median period of peripheral neuropathy was 149.5 days (vary: 1 to 692 days) in all sufferers together with these with ongoing neurologic occasions on the time of dying or knowledge cut-off.
Peripheral neuropathies occurred in 7% of sufferers in CARTITUDE-4 (0.5% Grade 3 to 4) and in 7% of sufferers in CARTITUDE-1 (2% Grade 3 to 4). Monitor sufferers for indicators and signs of peripheral neuropathies. Sufferers who expertise peripheral neuropathy might also expertise cranial nerve palsies or GBS.
Cranial Nerve Palsies occurred following therapy with CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, cranial nerve palsies occurred in 7% (19/285), together with Grade ‰¥3 in 1% (1/285) of the sufferers. Median time to onset of cranial nerve palsies was 21 days (vary: 17 to 101 days). Cranial nerve palsies resolved in 17 of 19 (89%) of sufferers with a median time to decision of 66 days (vary: 1 to 209 days). Median period of cranial nerve palsies was 70 days (vary: 1 to 262 days) in all sufferers together with these with ongoing neurologic occasions on the time of dying or knowledge cut-off. Cranial nerve palsies occurred in 9% of sufferers in CARTITUDE-4 (1% Grade 3 to 4) and in 3% of sufferers in CARTITUDE-1 (1% Grade 3 to 4).
Essentially the most frequent cranial nerve affected was the seventh cranial nerve. Moreover, cranial nerves III, V, and VI have been reported to be affected.
Monitor sufferers for indicators and signs of cranial nerve palsies. Take into account administration with systemic corticosteroids, relying on the severity and development of indicators and signs.
HEMOPHAGOCYTIC LYMPHOHISTIOCYTOSIS (HLH)/MACROPHAGE ACTIVATION SYNDROME (MAS): Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, HLH/MAS occurred in 1% (3/285) of sufferers. All occasions of HLH/MAS had onset inside 99 days of receiving CARVYKTI ®, with a median onset of 10 days (vary: 8 to 99 days) and all occurred within the setting of ongoing or worsening CRS. The manifestations of HLH/MAS included hyperferritinemia, hypotension, hypoxia with diffuse alveolar injury, coagulopathy and hemorrhage, cytopenia, and multi-organ dysfunction, together with renal dysfunction and respiratory failure.
Sufferers who develop HLH/MAS have an elevated threat of extreme bleeding. Monitor hematologic parameters in sufferers with HLH/MAS and transfuse per institutional tips. Deadly circumstances of HLH/MAS occurred following therapy with CARVYKTI ®.
HLH is a life-threatening situation with a excessive mortality fee if not acknowledged and handled early. Therapy of HLH/MAS needs to be administered per institutional requirements.
CARVYKTI ® REMS: Due to the chance of CRS and neurologic toxicities, CARVYKTI ® is obtainable solely by a restricted program beneath a Threat Analysis and Mitigation Technique (REMS) referred to as the CARVYKTI ® REMS.
Additional data is obtainable at https://www.carvyktirems.com or 1-844-672-0067.
PROLONGED AND RECURRENT CYTOPENIAS: Sufferers might exhibit extended and recurrent cytopenias following lymphodepleting chemotherapy and CARVYKTI ® infusion. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, Grade 3 or increased cytopenias not resolved by day 30 following CARVYKTI ® infusion occurred in 62% (176/285) of the sufferers 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 sufferers had a recurrence of Grade 3 or 4 lymphopenia, neutropenia, thrombocytopenia, and anemia respectively, after preliminary restoration of their Grade 3 or 4 cytopenia. Seventy-seven % (219/285) of sufferers had one, two, or three or extra recurrences of Grade 3 or 4 cytopenias after preliminary restoration of Grade 3 or 4 cytopenia. Sixteen and 25 sufferers had Grade 3 or 4 neutropenia and thrombocytopenia, respectively, on the time of dying.
Monitor blood counts previous to and after CARVYKTI ® infusion. Handle cytopenias with progress components and blood product transfusion help in line with native institutional tips.
INFECTIONS: CARVYKTI ® shouldn’t be administered to sufferers with lively an infection or inflammatory problems. Extreme, life-threatening, or deadly infections, occurred in sufferers after CARVYKTI ® infusion.
Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, infections occurred in 57% (163/285), together with ‰¥Grade 3 in 24% (69/285) of sufferers. 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 sufferers. Total, 5% (13/285) of sufferers had Grade 5 infections, 2.5% of which had been as a consequence of COVID-19. Sufferers handled with CARVYKTI ® had an elevated fee of deadly COVID-19 infections in comparison with the usual remedy arm.
Monitor sufferers for indicators and signs of an infection earlier than and after CARVYKTI ® infusion and deal with sufferers appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials in line with the usual institutional tips. Febrile neutropenia was noticed in 5% of sufferers after CARVYKTI ® infusion and could also be concurrent with CRS. Within the occasion of febrile neutropenia, consider for an infection and handle with broad-spectrum antibiotics, fluids, and different supportive care, as medically indicated. Counsel sufferers on the significance of prevention measures. Observe institutional tips for the vaccination and administration of immunocompromised sufferers with COVID-19.
Viral Reactivation: Hepatitis B virus (HBV) reactivation, in some circumstances leading to fulminant hepatitis, hepatic failure, and dying, can happen in sufferers with hypogammaglobulinemia. Carry out screening for Cytomegalovirus (CMV), HBV, hepatitis C virus (HCV), human immunodeficiency virus (HIV), or another infectious brokers if clinically indicated in accordance with medical tips earlier than assortment of cells for manufacturing. Take into account antiviral remedy to forestall viral reactivation per native institutional tips/medical observe.
HYPOGAMMAGLOBULINEMIA: can happen in sufferers receiving therapy with CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, hypogammaglobulinemia antagonistic occasion was reported in 36% (102/285) of sufferers; laboratory IgG ranges fell beneath 500mg/dl after infusion in 93% (265/285) of sufferers.
Hypogammaglobulinemia both as an antagonistic response or laboratory IgG stage beneath 500mg/dl, after infusion occurred in 94% (267/285) of sufferers handled. Fifty-six % (161/285) of sufferers obtained intravenous immunoglobulin (IVIG) submit CARVYKTI ® for both an antagonistic response or prophylaxis.
Monitor immunoglobulin ranges after therapy with CARVYKTI ® and administer IVIG for IgG
Use of Stay Vaccines: The security of immunization with reside viral vaccines throughout or following CARVYKTI ® therapy has not been studied. Vaccination with reside virus vaccines will not be really useful for a minimum of 6 weeks previous to the beginning of lymphodepleting chemotherapy, throughout CARVYKTI ® therapy, and till immune restoration following therapy with CARVYKTI ®.
HYPERSENSITIVITY REACTIONS occurred following therapy with CARVYKTI ®. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, hypersensitivity reactions occurred in 5% (13/285), all of which had been ‰¤ Grade 2. Manifestations of hypersensitivity reactions included flushing, chest discomfort, tachycardia, wheezing, tremor, burning sensation, non-cardiac chest ache, and pyrexia.
Severe hypersensitivity reactions, together with anaphylaxis, could also be because of the dimethyl sulfoxide (DMSO) in CARVYKTI ®. Sufferers needs to be rigorously monitored for two hours after infusion for indicators and signs of extreme response. Deal with promptly and handle sufferers appropriately in line with the severity of the hypersensitivity response.
SECONDARY MALIGNANCIES: Sufferers handled with CARVYKTI ® might develop secondary malignancies. Amongst sufferers receiving CARVYKTI ® within the CARTITUDE-1 & 4 research, myeloid neoplasms occurred in 5% (13/285) of sufferers (9 circumstances of myelodysplastic syndrome, 3 circumstances of acute myeloid leukemia, and 1 case of myelodysplastic syndrome adopted by acute myeloid leukemia). The median time to onset of myeloid neoplasms was 447 days (vary: 56 to 870 days) after therapy with CARVYKTI ®. Ten of those 13 sufferers died following the event of myeloid neoplasms; 2 of the 13 circumstances of myeloid neoplasm occurred after initiation of subsequent antimyeloma remedy. Circumstances of myelodysplastic syndrome and acute myeloid leukemia have additionally been reported within the post-marketing setting. T-cell malignancies have occurred following therapy of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T-cell immunotherapies, together with CARVYKTI ®. Mature T-cell malignancies, together with CAR-positive tumors, might current as quickly as weeks following infusions and should embrace deadly outcomes.
Monitor life-long for secondary malignancies. Within the occasion {that a} secondary malignancy happens, contact Janssen Biotech, Inc. at 1-800-526-7736 for reporting and to acquire directions on assortment of affected person samples.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES: As a result of potential for neurologic occasions, together with altered psychological standing, seizures, neurocognitive decline, or neuropathy, sufferers receiving CARVYKTI ® are in danger for altered or decreased consciousness or coordination within the 8 weeks following CARVYKTI ® infusion. Advise sufferers to chorus from driving and interesting in hazardous occupations or actions, similar to working heavy or doubtlessly harmful equipment throughout this preliminary interval, and within the occasion of latest onset of any neurologic toxicities.
ADVERSE REACTIONS
The most typical nonlaboratory antagonistic reactions (incidence higher than 20%) are pyrexia, cytokine launch syndrome, hypogammaglobulinemia, hypotension, musculoskeletal ache, fatigue, infections-pathogen unspecified, cough, chills, diarrhea, nausea, encephalopathy, decreased urge for food, higher respiratory tract an infection, headache, tachycardia, dizziness, dyspnea, edema, viral infections, coagulopathy, constipation, and vomiting. The most typical Grade 3 or 4 laboratory antagonistic reactions (incidence higher than or equal to 50%) embrace lymphopenia, neutropenia, white blood cell decreased, thrombocytopenia, and anemia.
Please learn full Prescribing Data, together with Boxed Warning, for CARVYKTI ®.
ABOUT CARVYKTI ® (CILTACABTAGENE AUTOLEUCEL; CILTA-CEL)
Ciltacabtagene autoleucel is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which includes reprogramming a affected person’s personal T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that specific BCMA. The cilta-cel CAR protein options two BCMA-targeting single area antibodies designed to confer excessive avidity in opposition to human BCMA. Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, enlargement, and elimination of goal cells.1
In December 2017, Legend Biotech entered into an unique worldwide license and collaboration settlement with Janssen Biotech, Inc. (Janssen), a Johnson & Johnson (NYSE:) firm, to develop and commercialize cilta-cel. In February 2022, cilta-cel was permitted by the U.S. Meals and Drug Administration (FDA) beneath the model identify CARVYKTI ® for the therapy of adults with relapsed or refractory a number of myeloma. In April 2024, cilta-cel was permitted for the second-line therapy of sufferers with relapsed/refractory myeloma who’ve obtained a minimum of one prior line of remedy together with a proteasome inhibitor, an immunomodulatory agent, and are refractory to lenalidomide.
In Could 2022, the European Fee (EC) granted conditional advertising authorization of CARVYKTI ® for the therapy of adults with relapsed and refractory a number of myeloma. In September 2022, Japan’s Ministry of Well being, Labour and Welfare (MHLW) permitted CARVYKTI ®. Cilta-cel was granted Breakthrough Remedy Designation within the U.S. in December 2019 and in China in August 2020. As well as, cilta-cel obtained a PRIority MEdicines (PRIME) designation from the European Fee in April 2019. Cilta-cel additionally obtained Orphan Drug Designation from the U.S. FDA in February 2019, from the European Fee in February 2020, and from the Prescription drugs and Medicinal Units Company (PMDA) in Japan in June 2020. In March 2022, the European Medicines Company’s Committee for Orphan Medicinal Merchandise really useful by consensus that the orphan designation for cilta-cel be maintained on the idea of medical knowledge demonstrating improved and sustained full response charges following therapy.
ABOUT CARTITUDE-4
CARTITUDE-4 (NCT04181827) is an ongoing, worldwide, randomized, open-label Part 3 research evaluating the efficacy and security of cilta-cel versus pomalidomide, bortezomib and dexamethasone (PVd) or daratumumab, pomalidomide and dexamethasone (DPd) in grownup sufferers with relapsed and lenalidomide-refractory a number of myeloma who obtained one to a few prior traces of remedy, together with a PI and an IMiD.2
ABOUT MULTIPLE MYELOMA
A number of myeloma is an incurable blood most cancers that begins within the bone marrow and is characterised by an extreme proliferation of plasma cells.3 In 2024, it’s estimated that greater than 35,000 individuals will probably be identified with a number of myeloma, and greater than 12,000 individuals will die from the illness within the U.S.4 Whereas some sufferers with a number of myeloma initially haven’t any signs, most sufferers are identified as a consequence of signs that may embrace bone issues, low blood counts, calcium elevation, kidney issues or infections.5
ABOUT LEGEND BIOTECH
Legend Biotech is a world biotechnology firm devoted to treating, and someday curing, life-threatening ailments. Headquartered in Somerset, New Jersey, we’re growing superior cell therapies throughout a various array of know-how platforms, together with autologous and allogeneic chimeric antigen receptor T-cell, gamma-delta T cell (gd T) and pure killer (NK) cell-based immunotherapy. From our three R&D websites around the globe, we apply these revolutionary applied sciences to pursue the invention of cutting-edge therapeutics for sufferers worldwide.
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CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
Statements on this press launch about future expectations, plans, and prospects, in addition to another statements concerning issues that aren’t historic information, represent forward-looking statements throughout the which means of The Personal Securities Litigation Reform Act of 1995. These statements embrace, however will not be restricted to, statements regarding Legend Biotech’s methods and aims; statements regarding CARVYKTI ®, together with Legend Biotech’s expectations for CARVYKTI ® and its therapeutic potential; statements associated to the potential outcomes from ongoing research within the CARTITUDE medical improvement program; and the potential advantages of Legend Biotech’s product candidates. The phrases anticipate, consider, proceed, may, estimate, count on, intend, might, plan, potential, predict, venture, ought to, goal, will, would and related expressions are meant to determine forward-looking statements, though not all forward-looking statements include these figuring out phrases. Precise outcomes might differ materially from these indicated by such forward-looking statements on account of numerous essential components. Legend Biotech’s expectations might be affected by, amongst different issues, uncertainties concerned within the improvement of latest pharmaceutical merchandise; sudden medical trial outcomes, together with on account of further evaluation of present medical knowledge or sudden new medical knowledge; sudden regulatory actions or delays, together with requests for extra security and/or efficacy knowledge or evaluation of information, or authorities regulation typically; sudden delays on account of actions undertaken, or failures to behave, by our third occasion companions; uncertainties arising from challenges to Legend Biotech’s patent or different proprietary mental property safety, together with the uncertainties concerned within the U.S. litigation course of; authorities, trade, and common product pricing and different political pressures; in addition to the opposite components mentioned within the Threat Components part of Legend Biotech’s Annual Report on Type 20-F filed with the Securities and Alternate Fee on March 19, 2024. Ought to a number of of those dangers or uncertainties materialize, or ought to underlying assumptions show incorrect, precise outcomes might range materially from these described on this press launch as anticipated, believed, estimated or anticipated. Any forward-looking statements contained on this press launch communicate solely as of the date of this press launch. Legend Biotech particularly disclaims any obligation to replace any forward-looking assertion, whether or not on account of new data, future occasions or in any other case.
INVESTOR CONTACT:
Jessie Yeung
Tel: (732) 956-8271
jessie.yeung@legendbiotech.com
PRESS CONTACT:
MaryAnn Ondish
Tel: (914) 552-4625
media@legendbiotech.com
REFERENCES
1 CARVYKTI™ Prescribing Data. Horsham, PA: Janssen Biotech, Inc.
2 ClinicalTrials.Gov. A Research Evaluating JNJ-68284528, a CAR-T Remedy Directed Towards B-cell Maturation Antigen (BCMA), Versus Pomalidomide, Bortezomib and Dexamethasone (PVd) or Daratumumab, Pomalidomide and Dexamethasone (DPd) in Individuals With Relapsed and Lenalidomide-Refractory A number of Myeloma (CARTITUDE-4). https://www.clinicaltrials.gov/research/NCT04181827. Accessed March 2024.
3 American Most cancers Society. What’s A number of Myeloma?. Accessible at: https://www.most cancers.org/most cancers/varieties/multiple-myeloma/about/what-is-multiple-myeloma.html. Accessed March 2024.
4 American Most cancers Society. Key Statistics About A number of Myeloma. Accessible at: https://www.most cancers.org/most cancers/varieties/multiple-myeloma/about/key-statistics.html. Accessed March 2024
5 American Most cancers Society. A number of myeloma: early detection, prognosis, and staging. Accessible at: https://www.most cancers.org/content material/dam/CRC/PDF/Public/8740.00.pdf. Accessed March 2023.
