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DRUG:

Carvykti (ciltacabtagene autoleucel)

i
Other names: JNJ-4528, JNJ 4528, cilta-cel, JNJ4528, JNJ68284528, LCARB38M, LCAR B38M, LCAR-B38M, anti-BCMA CAR-T, LCAR-B38M CAR-T, JNJ-68284528, JNJ 68284528
Company:
J&J, Legend Biotech
Drug class:
BCMA-targeted CAR-T immunotherapy
Related drugs:
7d
How we manage multiple myeloma with clonal hematopoiesis of indeterminate potential (CHIP): a case report. (PubMed, Ann Transl Med)
After four cycles of cyclophosphamide, bortezomib, and dexamethasone therapy, he achieved a partial response, followed by complete hematologic response (CR) post eight cycles of lenalidomide, dexamethasone, and bortezomib therapy...Following failure of >4 lines of therapy, he received chimeric antigen receptor T (CAR-T) cell therapy (ciltacabtagene autoleucel) for salvage...This case report highlights MM management complexities in CHIP presence, suggesting potential utility of HSCT and CAR-T cell therapy. Prospective studies are necessary to evaluate the safety and efficacy of these therapies in myeloma patients with concurrent CHIP, aiming to optimize treatment strategies and improve outcomes in this challenging clinical context.
Journal • IO biomarker
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PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
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PPM1D mutation
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lenalidomide • bortezomib • cyclophosphamide • dexamethasone • Carvykti (ciltacabtagene autoleucel)
8d
Long-Term Benefits in Patient-Reported Outcomes and Time to Next Anti-Myeloma Therapy of Ciltacabtagene Autoleucel (Cilta-cel) Versus Standard of Care for Patients with Lenalidomide-Refractory Multiple Myeloma: Results from the Phase 3 Cartitude-4 Clinical Trial (ASH 2024)
"Background: Ciltacabtagene autoleucel (cilta-cel) demonstrated superior progression-free survival (PFS) and overall survival compared to standard of care (SOC; pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone) in patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior lines of therapy (LOTs) in the phase 3 CARTITUDE-4 trial. The increase in the TTNT and sustained benefits in PROs, along with prolonged survival, support cilta-cel as a new SOC treatment for MM patients who are refractory to lenalidomide and have received 1-3 prior LOTs. Importantly, with ~3 years of follow-up, a single infusion of cilta-cel provided patients with a longer delay in worsening of MM related symptoms, functional impacts, and GHS/QoL. The totality of clinical and patient-reported evidence demonstrates the significant benefit of cilta-cel."
P3 data • Clinical • Patient reported outcomes
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lenalidomide • bortezomib • Darzalex (daratumumab) • dexamethasone • pomalidomide • Carvykti (ciltacabtagene autoleucel)
18d
CAR-HiRiSMM: Ciltacabtagene Autoleucel in High-Risk Smoldering Multiple Myeloma (clinicaltrials.gov)
P2, N=20, Recruiting, PETHEMA Foundation | Not yet recruiting --> Recruiting
Enrollment open
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CD4 (CD4 Molecule)
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Carvykti (ciltacabtagene autoleucel)
1m
MonumenTAL-8: A Study of Ciltacabtagene Autoleucel and Talquetamab for the Treatment of Participants With High-Risk Multiple Myeloma (clinicaltrials.gov)
P2, N=30, Recruiting, Janssen Research & Development, LLC | Trial completion date: Apr 2028 --> Feb 2027
Trial completion date
|
lenalidomide • Darzalex (daratumumab) • dexamethasone • Carvykti (ciltacabtagene autoleucel) • Talvey (talquetamab-tgvs)
1m
New P1 trial
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cyclophosphamide • Carvykti (ciltacabtagene autoleucel)
2ms
Enrollment closed • CAR T-Cell Therapy
|
lenalidomide • bortezomib • cyclophosphamide • dexamethasone • fludarabine IV • Carvykti (ciltacabtagene autoleucel)
2ms
Enrollment open
|
lenalidomide • Darzalex (daratumumab) • dexamethasone • Carvykti (ciltacabtagene autoleucel) • Talvey (talquetamab-tgvs)
3ms
New P2 trial
|
lenalidomide • bortezomib • cyclophosphamide • fludarabine IV • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • Carvykti (ciltacabtagene autoleucel) • Talvey (talquetamab-tgvs) • Tecvayli (teclistamab-cqyv)
3ms
New P2 trial
|
CD4 (CD4 Molecule)
|
Carvykti (ciltacabtagene autoleucel)
3ms
New P2 trial
|
lenalidomide • Darzalex (daratumumab) • dexamethasone • Carvykti (ciltacabtagene autoleucel) • Talvey (talquetamab-tgvs)
4ms
Enrollment open • Enrollment change
|
lenalidomide • bortezomib • dexamethasone • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • Carvykti (ciltacabtagene autoleucel) • dexamethasone injection
5ms
Trial primary completion date • CAR T-Cell Therapy
|
lenalidomide • bortezomib • dexamethasone • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • Carvykti (ciltacabtagene autoleucel) • dexamethasone injection
5ms
Trial primary completion date • CAR T-Cell Therapy
|
lenalidomide • bortezomib • cyclophosphamide • dexamethasone • pomalidomide • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • Carvykti (ciltacabtagene autoleucel)
5ms
Indolent CD4+ CAR T-Cell Lymphoma after Cilta-cel CAR T-Cell Therapy. (PubMed, N Engl J Med)
In addition, numerous genetic alterations that may have contributed to malignant transformation were identified in the tumor sample. (Funded by MedStar Georgetown University Hospital.).
Journal • CAR T-Cell Therapy
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CD4 (CD4 Molecule)
|
Carvykti (ciltacabtagene autoleucel)
6ms
Beyond BCMA: the next wave of CAR T cell therapy in multiple myeloma. (PubMed, Front Oncol)
The current Food and Drug Administration approved CAR T cell therapies idecabtagene vicleucel and ciltacabtagene autoleucel both target B cell maturation antigen (BCMA), which is expressed on the surface of malignant plasma cells. CAR T cells targeting these antigens, alone or in combination with anti-BCMA approaches, appear to be highly promising as they move from preclinical studies to early phase clinical trials. This review summarizes the current data with novel CAR T cell targets beyond BCMA that have the potential to enter the treatment landscape in the near future.
Review • Journal • CAR T-Cell Therapy
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CD38 (CD38 Molecule) • SLAMF7 (SLAM Family Member 7)
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Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel)
6ms
Antigen escape as a shared mechanism of resistance to BCMA-directed therapies in multiple myeloma. (PubMed, Blood)
Prior therapy-mediated loss of plasma cell BCMA expression before teclistamab treatment, measured by immunohistochemistry, was observed in 3 patients, none of whom responded to teclistamab, and one of whom also did not respond to ciltacabtagene autoleucel. Whole exome sequencing of tumor DNA from one patient revealed biallelic loss of TNFRSF17 following treatment with belantamab mafodotin. Low-to-undetectable peripheral blood soluble BCMA levels correlated with the absence of BCMA expression by bone marrow plasma cells. Thus, although rare, loss of BCMA expression following TNFRSF17 gene deletions can occur following any BCMA-directed therapy and prevents response to subsequent anti-BCMA-directed treatments, underscoring the importance of verifying the presence of a target antigen.
Journal • IO biomarker
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TNFRSF17 (TNF Receptor Superfamily Member 17)
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Blenrep (belantamab mafodotin-blmf) • Carvykti (ciltacabtagene autoleucel) • Tecvayli (teclistamab-cqyv)
7ms
Efficacy and safety of bendamustine for lymphodepletion before lisocabtagene maraleucel. (PubMed, J Hematol Oncol)
Bendamustine has been retrospectively shown to be an effective and safe lymphodepletion regimen prior to the anti-CD19 chimeric antigen receptor T cell (CART) products tisagenlecleucel and axicabtagene ciloleucel, as well as the anti-BCMA CART products idecabtagene vicleucel and ciltacabtagene autoleucel. Neutropenia ≥ grade 3 was observed in 29.0% of patients; thrombocytopenia ≥ grade 3 occurred in 9.7%. In conclusion, bendamustine lymphodepletion before liso-cel appears to be a strategy that can drive tumor responses while ensuring a mild toxicity profile.
Journal
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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Yescarta (axicabtagene ciloleucel) • Breyanzi (lisocabtagene maraleucel) • Kymriah (tisagenlecleucel-T) • bendamustine • Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel)
7ms
Long-term remission and survival in patients with relapsed or refractory multiple myeloma after treatment with LCAR-B38M CAR T cells: 5-year follow-up of the LEGEND-2 trial. (PubMed, J Hematol Oncol)
These data, representing the longest follow-up of BCMA-redirected CAR T-cell therapy to date, demonstrate long-term remission and survival with LCAR-B38M for advanced myeloma.
Journal • CAR T-Cell Therapy
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CD8 (cluster of differentiation 8) • CD4 (CD4 Molecule)
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cyclophosphamide • fludarabine IV • Carvykti (ciltacabtagene autoleucel)
7ms
Phase classification • CAR T-Cell Therapy
|
Carvykti (ciltacabtagene autoleucel)
9ms
A Study of JNJ-68284528 Out-of-Specification (OOS) for Commercial Release in Participants With Multiple Myeloma (clinicaltrials.gov)
P2, N=86, Completed, Janssen Scientific Affairs, LLC | Active, not recruiting --> Completed
Trial completion
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cyclophosphamide • fludarabine IV • Carvykti (ciltacabtagene autoleucel)
10ms
Neutrophil activation and clonal CAR-T re-expansion underpinning cytokine release syndrome during ciltacabtagene autoleucel therapy in multiple myeloma. (PubMed, Nat Commun)
Notably, CAR-T re-expansion is found in three patients, including a fatal case characterized by somatic TET2-mutation, clonal expanded cytotoxic CAR-T, broadened cytokine profiles and irreversible hepatic toxicity. Together, our findings show that a latent phase with distinct immunological changes precedes manifest CRS, providing an optimal window and potential targets for CRS therapeutic intervention and that CAR-T re-expansion warrants close clinical attention and laboratory investigation to mitigate the lethal risk.
Journal • IO biomarker
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TET2 (Tet Methylcytosine Dioxygenase 2)
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TET2 mutation
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Carvykti (ciltacabtagene autoleucel)
11ms
CARAMEL: CAR-T Cell Therapy in RelApsed/Refractory Myeloma With ExtrameduLlary Disease - an in Vivo Imaging and Molecular Monitoring Study (clinicaltrials.gov)
P1, N=10, Recruiting, Peter MacCallum Cancer Centre, Australia | N=15 --> 10 | Trial completion date: Aug 2025 --> Jan 2027 | Trial primary completion date: Aug 2025 --> Jan 2026
Enrollment change • Trial completion date • Trial primary completion date • CAR T-Cell Therapy
|
Carvykti (ciltacabtagene autoleucel)
11ms
Update on the current and future use of CAR-T to treat multiple myeloma. (PubMed, Eur J Haematol)
This review will explore the earliest CAR-T trials in myeloma, discuss important issues involved in CAR-T manufacturing and processing, as well as review current clinical trials that led to the approval of the two commercially available CAR-T products, Idecabtagene vicleucel and ciltacabtagene autoleucel. The next generation of MM-specific CAR-T will likely include new targets such as G-protein-coupled receptor class C, Group 5, member D (GPRC5D) and signaling lymphocyte activation molecular Family 7 (SLAMF7). The role of CAR-T in the treatment of MM will undoubtedly increase exponentially in the next decade.
Review • Journal • IO biomarker
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SLAMF7 (SLAM Family Member 7)
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Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel)
11ms
Enrollment open
|
Carvykti (ciltacabtagene autoleucel)
11ms
Trial completion date • CAR T-Cell Therapy
|
lenalidomide • bortezomib • cyclophosphamide • dexamethasone • fludarabine IV • Carvykti (ciltacabtagene autoleucel)
11ms
Trial completion date • CAR T-Cell Therapy
|
lenalidomide • bortezomib • dexamethasone • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • Carvykti (ciltacabtagene autoleucel) • dexamethasone injection
12ms
Clinician and Administrator Perspectives on Chimeric Antigen Receptor (CAR) T-Cell Therapy Outpatient Administration in Relapsed or Refractory Multiple Myeloma (RRMM) in the United States (US): A Qualitative Study (ASH 2023)
Over 50% of the centers interviewed have recently started to administer tocilizumab to treat mild grade 1 cytokine release syndrome (CRS) in an outpatient setting. Overall, this study further supports the notion that centers can safely administer cilta-cel in an outpatient setting, if appropriate infrastructure is in place. Additional best practices for new outpatient sites include adequate infrastructure, SOPs, a well-trained and multidisciplinary team, and education of patients and caregivers (Table 1). Outpatient management and earlier intervention for low-grade AEs is currently evolving, with more real-world research required.
Clinical
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Actemra IV (tocilizumab) • Carvykti (ciltacabtagene autoleucel)
12ms
Unveiling the Digital Landscape of CAR-T Therapies in Multiple Myeloma Using Social Media Insights (ASH 2023)
Introduction: The rapid evolution of novel chimeric antigen receptor T-cell (CAR-T) therapies, including Carvykti (ciltacabtagene autoleucel) and Abecma (idecabtagene vicleucel), have revolutionized the treatment landscape for multiple myeloma (MM) patients...Management strategies mentioned included earlier and more aggressive supportive care, the use of cytokine-targeting therapies such as tocilizumab for any grade CRS, steroids such as dexamethasone for immune effector cell-associated neurotoxicity syndrome, and prophylactic antiseizure medications for all patients regardless of neurotoxicity... The study findings highlight the importance of demystifying cost perceptions against the added value to patients, HCPs and payers, and implementing comprehensive post-CAR-T care protocols aligned with the concerns expressed in social media discussions for improvement in CAR-T therapies for multiple myeloma. By leveraging the power of social media data, this study offers valuable real-world insights that can inform clinical decision-making, enhance patient-centered care, and contribute to the development of strategies to overcome challenges associated with CAR-T therapies in multiple myeloma.
IO biomarker
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dexamethasone • Actemra IV (tocilizumab) • Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel)
12ms
Heterogeneity in Access and Toxicity Management of Commercially Available BCMA-Directed CAR-T and Bispecific T-Cell Engager Therapy Among the International Myeloma Community (ASH 2023)
This has led to the approval of idecabtagene vicleucel, ciltacabtagene autoleucel and teclistamab by the FDA, EMA and other regulatory agencies...Tocilizumab was used as cytokine release syndrome (CRS) prophylaxis only by one responder. Keppra neurologic prophylaxis was used by 47... Trends of CAR-T and BiTE therapy use and patterns of concurrent prophylactic and supportive care in MM vary widely among academic centers across the globe, demonstrating a need for further understanding of toxicity pathogenesis, toxicity management and consistent guidelines. This survey also demonstrates the great unmet need for access beyond urban centers among the international myeloma community. Prospective studies and claims data analysis should be utilized to evaluate the longitudinal cost of care, quality of life, duration of response and management of infectious disease, neurological or related complications of CAR-T and bispecific TCE therapies.
Adverse events
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CD4 (CD4 Molecule)
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Actemra IV (tocilizumab) • Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel) • Tecvayli (teclistamab-cqyv)
12ms
Using Real-World Remanufacturing and Recollection Data to Optimize Time-to-Treatment in Patients with out-of-Specification Ciltacabtagene Autoleucel (ASH 2023)
Our findings on remanufacturing and recollection outcomes may inform physician decisions and help optimize time-to-treatment in patients receiving cilta-cel. Additional studies (eg, NCT05347485) are underway to evaluate the safety and efficacy of OOS cilta-cel.
Clinical • Real-world evidence • Real-world
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Carvykti (ciltacabtagene autoleucel)
12ms
CAR+ T-Cell Lymphoma Post Ciltacabtagene Autoleucel Therapy for Relapsed Refractory Multiple Myeloma (ASH 2023)
26) vs standard of care in lenalidomide-refractory patients with multiple myeloma and 1-3 prior lines of therapy...The patient received CHOEP-21 (cyclophosphamide-doxorubicin-vincristine-prednisone-etoposide) and achieved metabolic CR but relapsed soon after treatment was stopped. Subsequent treatment with gemcitabine-dexamethasone-cisplatin-alemtuzumab was followed by consolidation with fludarabine plus melphalan and matched allogeneic stem cell transplant... To our knowledge, this is the first case of CAR+ TCL occurring after infusion of a CAR-T therapy produced via lentiviral transduction (cilta-cel). This rare malignancy was potentially driven by genetic mutations (e. g.
Tumor mutational burden • IO biomarker
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ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • CD8 (cluster of differentiation 8) • TNFRSF8 (TNF Receptor Superfamily Member 8) • TET2 (Tet Methylcytosine Dioxygenase 2) • CD34 (CD34 molecule) • JAK3 (Janus Kinase 3) • NCAM1 (Neural cell adhesion molecule 1) • CD7 (CD7 Molecule) • CD2 (CD2 Molecule) • NFKB2 (Nuclear Factor Kappa B Subunit 2)
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TMB-L • TET2 mutation • JAK3 mutation
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cisplatin • gemcitabine • lenalidomide • doxorubicin hydrochloride • cyclophosphamide • etoposide IV • Campath (alemtuzumab) • vincristine • prednisone • dexamethasone • melphalan • fludarabine IV • Carvykti (ciltacabtagene autoleucel)
12ms
Patient-Reported Outcomes Among Patients with Triple-Class Refractory Multiple Myeloma in Real-World Clinical Practice: A Prospective, Multi-Site Observational Study (ASH 2023)
N=24 patients initiated a CAR-T therapy as their index therapy (equally split between ide-cel and cilta-cel); the remaining N=31 patients predominantly initiated a treatment regimen containing an IMiD (52%), a PI (55%), an anti-CD38 antibody (13%), or an alkylating agent (36%). Patients did, however, directly report improvement in their disease state as early as Month 1 based on the PGIC. Non-CART patients generally showed a QOL plateau with some modest improvement in disease symptoms which was also reflected in their self-reported assessment of disease state improvement based on the PGIC.
Clinical • Observational data • Real-world evidence • Patient reported outcomes • Real-world
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Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel)
12ms
Trial completion date • Trial primary completion date
|
lenalidomide • bortezomib • cyclophosphamide • dexamethasone • fludarabine IV • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • Carvykti (ciltacabtagene autoleucel)
12ms
A safety review of recently approved and emerging drugs for patients with relapsed or refractory multiple myeloma. (PubMed, Expert Opin Drug Saf)
We review common toxicities associated with agents approved for RRMM in the past 5 years, including the anti-CD38 monoclonal antibody isatuximab, the antibody-drug conjugate belantamab mafodotin, the bispecific antibody teclistamab, the chimeric antigen receptor (CAR) T cell products idecabtagene vicleucel and ciltacabtagene autoleucel, the selective inhibitor of nuclear export compound selinexor, and the drug-peptide conjugate melflufen, as well as toxicities associated with emerging agents for RRMM including additional bispecific antibodies, the BCL-2 inhibitor venetoclax, and the cereblon E3 ligase modulators iberdomide and mezigdomide. We searched the published literature using PubMed, plus congress abstracts, for the above list of drug names or classes and 'myeloma.' Optimal management of toxicities associated with these recently approved and emerging therapies will be critical in maximizing clinical benefit and aiding widespread adoption in routine clinical practice. We summarize current recommendations and guidelines and provide expert insights into supportive care requirements.
Review • Journal • Adverse events
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CRBN (Cereblon)
|
Venclexta (venetoclax) • Xpovio (selinexor) • Sarclisa (isatuximab-irfc) • Melflufen (melphalan flufenamide) • Blenrep (belantamab mafodotin-blmf) • Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel) • Tecvayli (teclistamab-cqyv) • iberdomide (CC-220) • mezigdomide (CC-92480)
12ms
Trial completion date • CAR T-Cell Therapy
|
lenalidomide • bortezomib • dexamethasone • Darzalex Faspro (daratumumab and hyaluronidase-fihj) • Carvykti (ciltacabtagene autoleucel) • dexamethasone injection
1year
Cost per Responder Analysis of Patients with Lenalidomide-Refractory Multiple Myeloma Who Received Cilta-Cel from the Cartitude-4 Trial (ASH 2023)
In the phase 3 trial, CARTITUDE-4 (NCT04181827), cilta-cel demonstrated better efficacy than physician's choice (daratumumab plus pomalidomide and dexamethasone [DPd] or pomalidomide plus bortezomib and dexamethasone [PVd]) with an overall response rate (ORR) of 84.6% versus 67.3% and ≥complete response (CR) of 73.1% versus 21.8% (San-Miguel et al. Overall, cilta-cel offers substantial clinical and economic benefit for patients with RRMM. The CPR analysis of data from CARTITUDE-4 estimated that, for patients with RRMM, cost per complete responder, and cost per month in PFS for cilta-cel were remarkably lower compared to physician's choice (DPd or PVd). Treatment acquisition and subsequent treatment costs appear to be key drivers for total direct medical costs.
Clinical • HEOR
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lenalidomide • bortezomib • Darzalex (daratumumab) • dexamethasone • pomalidomide • Carvykti (ciltacabtagene autoleucel)
1year
Sequential T-Cell Engagement for Myeloma ("STEM") Trial: A Phase 2 Study of Cevostamab Consolidation Following BCMA CAR T Cell Therapy (ASH 2023)
Background and significance: The BCMA-targeted CAR T products idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel) are currently approved for relapsed/refractory multiple myeloma (RRMM) patients with ≥4 prior lines of therapy, including an IMID, proteasome inhibitor, and CD38 antibody. This phase 2 study is exploring the efficacy, safety, and feasibility of cevostamab consolidation following BCMA-directed CAR T cell therapy for RRMM, with the goal of sequential T cell engagement against 2 different antigens to eliminate residual disease. Accrual started in July 2023.
CAR T-Cell Therapy • P2 data • IO biomarker
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clonoSEQ
|
Abecma (idecabtagene vicleucel) • Carvykti (ciltacabtagene autoleucel) • cevostamab (RG6160)