Carvykti (ciltacabtagene autoleucel) / J&J, Legend Biotech - LARVOL DELTA

Cilta-Talq Fusion Study: A Phase 1b Study of Talquetamab Bridging Therapy Followed by Ciltacabtagene Autoleucel in Patients With Relapsed/Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=31 | Not yet recruiting | Sponsor: Medical College of Wisconsin

New P1 trial • Hematological Malignancies • Multiple Myeloma • Oncology

Activity of CAR-T cells and bispecific antibodies in multiple myeloma with extramedullary involvement. (PubMed, Blood Cancer J) - "We retrospectively analyzed 80 patients with EMD not adjacent to the bone treated with ide-cel, cilta-cel, teclistamab, or talquetamab at three academic centers in Germany. Visceral and soft tissue manifestations responded significantly less frequently than EMD in other locations. With significantly higher response rates, deeper remissions, and longer mPFS, our retrospective data suggest CAR T cells may provide a meaningful benefit in EMD."

IO biomarker • Journal • Retrospective data • Hematological Malignancies • Multiple Myeloma • Oncology

Ciltacabtagene Autoleucel versus Idecabtagene Vicleucel for Treatment of Patients with Relapsed or Refractory Multiple Myeloma: A Systematic Review and Meta-analysis (ESMO 2025) - No abstract available

Retrospective data • Review • Hematological Malignancies • Multiple Myeloma • Oncology

CARTITUDE-4: 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 (clinicaltrials.gov) - P3 | N=419 | Active, not recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jun 2027 ➔ Apr 2029

IO biomarker • Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Low Occurrence of Ocular Adverse Events after CAR-T Cell Therapy. (PubMed, Ocul Oncol Pathol) - "Billing codes were used to identify patients receiving autologous CAR-T therapy approved by the US Food and Drug Administration (FDA) for the treatment of a hematological malignancy: tisagenlecleucel, brexucabtagene autoleucel, lisocabtagene maraleucel, ciltacabtagene autoleucel, idecabtagene vicleucel, or axicabtagene ciloleucel. In the period of 6 months following CAR-T therapy infusion, o-AEs were rare in patients receiving CAR-T cell therapy, indicating that patients without existing eye conditions do not need routine prescreening or directed follow-up after treatment, unless symptomatic. Ongoing monitoring and reporting of ocular adverse events will be important given the durable effects of CAR-T therapy in the treatment of hematologic cancers as well as increasing indications for CAR-T therapy in malignant and nonmalignant disease."

Adverse events • Journal • Conjunctivitis • Dry Eye Disease • Hematological Disorders • Hematological Malignancies • Herpes Zoster • Keratitis • Leukemia • Lymphoma • Ocular Infections • Ocular Inflammation • Oncology • Ophthalmology • Optic Neuritis • Uveitis

Legend Biotech Reports Strong Sales for CARVYKTI in Q2 2025 (TipRanks) - "Legend Biotech, an associate of Genscript Biotech, announced that its product CARVYKTI generated approximately $439 million in net trade sales for the quarter ending June 30, 2025. This financial performance is linked to a collaboration with Janssen Biotech, highlighting the product’s market success and potential impact on Genscript’s financial standing and industry positioning."

Sales • Multiple Myeloma

Post-marketing Safety Assessment of CAR T-cell Therapies: Analysis of Individual Case Safety Reports in the VigiBase. (PubMed, Ther Innov Regul Sci) - "Our study provides an overall exploration of the post-marketing safety profiles of currently approved CAR-T cell therapies. The significant proportion of fatalities occurred in accordance with approved indications, emphasizes the need for ongoing investigation into ADRs with fatal outcomes, particularly in the pediatric population."

Journal • P4 data • Hematological Disorders • Hematological Malignancies • Oncology • Pediatrics

Multiple Myeloma Unpacked (ICML 2025) - P3 | "Several other phase II studies have explored the efficacy of triplet regimens incorporating Rd as a backbone, combined with agents such as elotuzumab [30], ixazomib [31], or carfilzomib [32] as well as quadruplet regimen including daratumumab and carfilzomib [33]...The landscape of induction treatment has evolved with the incorporation of the anti-CD38 monoclonal antibody daratumumab (D) into the triplet bortezomib-thalidomide-dexamethasone (VTd) and, more recently, bortezomib-lenalidomide-dexamethasone (VRd)...In transplant-ineligible patients, VRd [45], daratumumab-lenalidomide-dexamethasone (DRd) [46, 47] and daratumumab-bortezomib-melphalan-prednisone (DVMP) [48, 49] have been the standards of cares for years...The FDA approval of isatuximab-bortezomib-lenalidomide-dexamethasone (Isa-VRd), based on the results of the IMROZ study [38], which demonstrated the superiority of Isa-VRd over VRd in terms of MRD negativity and PFS, introduces a new SoC...Consequently,..."

IO biomarker • Hematological Malignancies • Multiple Myeloma • Oncology • Plasmacytoma • Smoldering Multiple Myeloma • B2M • CRBN • CTCs • XPO1

Cilta-cel salvages ide-cel failure in relapsed multiple myeloma by driving distinct immune responses. (PubMed, medRxiv) - "Our results present important clinical evidence that cilta-cel can serve as an effective salvage treatment following ide-cel failure. By providing a direct patient-matched comparison between two CAR therapies, our study uncovers important insights into both CAR T-cell intrinsic properties and immune environmental factors that contribute to effective BCMA CAR T-cell treatment."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • CD4 • CD8 • IL2

Chimeric antigen receptor T-cell therapy for multiple myeloma. (PubMed, Curr Opin Oncol) - "This is an exciting area with countless studies investigating novel CAR T constructs and sequencing in hopes of further extending and improving our patients' lives."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology • Smoldering Multiple Myeloma

CARTINUE: A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel (clinicaltrials.gov) - P4 | N=295 | Recruiting | Sponsor: Janssen Research & Development, LLC | Trial completion date: Jul 2037 ➔ Oct 2037

Trial completion date • Hematological Malignancies • Multiple Myeloma • Oncology

Resistance Mechanisms to BCMA Targeting Bispecific Antibodies and CAR T-Cell Therapies in Multiple Myeloma. (PubMed, Cells) - "In this review, we examine the current landscape of BCMA-directed therapies, including Idecabtagene Vileucel, Ciltacabtagene Autoleucel, Teclistamab, and Elranatamab and explore the multifactorial mechanisms driving resistance. Additionally, we discuss the role of therapy sequencing, emphasizing how prior exposure to BsAbs or CAR T-cell therapies may influence the efficacy of subsequent treatments. A deeper understanding of resistance biology, supported by integrated immune and genomic profiling, is essential to optimizing therapeutic durability and ultimately improve patient outcomes for patients with MM."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Treatment-related adverse events of chimeric antigen receptor-T therapies for cancers in clinical trials: a systematic review and meta-analysis. (PubMed, EClinicalMedicine) - "Ciltacabtagene autoleucel was associated with a lower mean incidence of all-grade adverse events (Risk ratio [RR], 1.00; 95% CI, 0.99-1.01; Rank-score, 0.6341; I 2 = 0.0%) and tisagenlecleucel were associated with lower grade 3 or higher adverse events (RR, 0.93; 95% CI, 0.86-1.02; Rank-score, 0.9738; I 2 = 78.4%) compared with standard care and CAR T-cell therapies. Our study provides comprehensive data on adverse events associated with different CAR-T cell treatments, maps a complete toxicity profile, and provides an important reference for clinicians to select and manage anti-cancer therapies. This study was supported by the Changsha Natural Science Foundation of Hunan Provincial of China (Grant/Award Number: kq2208376 to HZ)."

Adverse events • Journal • Retrospective data • Hematological Disorders • Hematological Malignancies • Neutropenia • Oncology • Solid Tumor

Carvykti: Expiry of patents in US related to composition-of-matter in 2036 (J&J) - Q2 2025 Results

Patent • Hematological Malignancies • Multiple Myeloma • Oncology

Sequential BCMA CAR-T Cell Therapy in Refractory Multiple Myeloma. (PubMed, Blood Adv) - "We analyzed 10 heavily pretreated MM patients at three medical centers treated with the commercially approved CAR-T product ide-cel in a real-world setting. Upon relapse, all patients received cilta-cel as a second CAR-T infusion, with bridging treatments permitted between both therapies...Two of three relapsing patients died within a year and showed no further response to bispecific antibody treatment. This study provides the first real-world evidence that sequential treatment with two different commercially approved BCMA CAR-T products is both feasible and effective, particularly in patients with prolonged responses to initial BCMA CAR-T therapy."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Cytopenias and infections following ciltacabtagene autoleucel in heavily-pretreated relapsed or refractory multiple myeloma. (PubMed, Haematologica) - "Ciltacabtagene autoleucel (cilta-cel) was FDA-approved in February 2022 for the treatment of relapsed/refractory multiple myeloma after 4 lines of therapy. Later infections between days 31-100 and after day 100 were mostly viral (59% and 60%), with only 32% and 12% being grade ≥3 at each time period. On univariate analysis, worse ECOG performance status at lymphodepletion, higher maximum grade of CRS, delayed neurotoxicity, steroid and anakinra use, and lower IgA levels at day 90 were associated with severe infections."

Journal • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Oncology • Thrombocytopenia • CD34

Revolutions at the frontline of multiple myeloma treatment: lessons and challenges to finding a cure. (PubMed, Front Oncol) - "Idecabtagene vicleucel and ciltacabtagene autoleucel are chimeric antigen receptor (CAR) T-cell immunotherapies that attach to the extracellular domain of the B-cell maturation antigen (BCMA) and have demonstrated significant response rates in heavily-treated patients. Agents that target BCMA and G protein-coupled receptor class C group 5 member D (GPRC5D) demonstrate impressive clinical responses, while early-phase trials targeting FcRH5 are promising. Here, we provide a comprehensive overview of their individual efficacy, adverse effects, and limitations that impact broader application."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology • Solid Tumor

Immune correlates of anti-BCMA CAR-T products idecabtagene vicleucel and ciltacabtagene autoleucel in a real-world cohort of patients with multiple myeloma. (PubMed, Nat Commun) - "This in-depth biomonitoring report following real-world cilta-cel or ide-cel highlights intrinsic biological differences between BCMA-targeting CAR T products, potentially explaining differences in clinical activity and toxicity. Our findings may guide optimization of cellular immunotherapy strategies in MM."

IO biomarker • Journal • Real-world evidence • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • CD27 • CD4 • HAVCR2

Current Anti-Myeloma Chimeric Antigen Receptor-T Cells: Novel Targets and Methods. (PubMed, Balkan Med J) - "In 2021, idecabtagene vicleucel, a BCMA-targeting agent, became the first CAR-T therapy approved for relapsed/refractory MM, marking a significant milestone in MM treatment. Subsequently, ciltacabtagene autoleucel has also been approved...To address these challenges, strategies such as BCMA non-targeted or dual-targeted CAR-T, memory T cells, humanized CAR-T, and rapidly manufactured PHE885 cells have been developed...In conclusion, studies are exploring the use of CAR-T at an earlier stage, including at diagnosis, with an aim to replace ASCT. CAR-T has introduced a new dimension to MM treatment; however, limited efficacy in high-risk MM and the emergence of resistance to CAR-T remain key challenges to be addressed."

Journal • Review • Gene Therapies • Hematological Malignancies • Multiple Myeloma • Oncology • CD70 • CTAG1B • NCAM1 • SDC1

Survival Outcomes with Cilta-cel Versus Conventional Treatment Regimens for Patients with Lenalidomide-Refractory Multiple Myeloma Using Inverse Probability of Treatment Weighting. (PubMed, Adv Ther) - P3 | "This updated analysis confirms previously observed significant superiority of PFS and response outcomes of cilta-cel while showing significant OS benefit compared with common regimens for this population. These findings support cilta-cel as an effective treatment for lenalidomide-refractory RRMM patients as early as second line."

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

FDA Eliminates Risk Evaluation and Mitigation Strategies (REMS) for Autologous Chimeric Antigen Receptor (CAR) T cell Immunotherapies (FDA) - "A REMS is a safety program that the FDA can require for certain medications with serious safety concerns to help ensure the benefits of the medication outweigh its risks. Because of the risks of cytokine release syndrome (CRS) and neurological toxicities, since their initial approvals until June 2025, the following currently approved (listed alphabetically by trade name) BCMA- or CD19-directed autologous CAR T cell immunotherapies were available through a restricted program under a REMS: Abecma (idecabtagene vicleucel), Breyanzi (lisocabtagene maraleucel), Carvykti (ciltacabtagene autoleucel), Kymriah (tisagenlecleucel), Tecartus (brexucabtagene autoleucel), Yescarta (axicabtagene ciloleucel)."

FDA event • Oncology

Progressive Multifocal Leukoencephalopathy in Chimeric Antigen Receptor T-Cell Therapy Recipients: A Case Study. (PubMed, J Adv Pract Oncol) - "Here, we present a patient treated with ciltacabtagene autoleucel for refractory MM who presented with PML around 2 months after receiving CAR T-cell therapy...Treatments for PML are mostly focused on reconstituting immunity. However, no adequate treatment strategy for PML has yet been established and further research is needed."

Journal • CNS Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Rare Diseases

Dasatinib and Quercetin With CAR-T Therapy for the Treatment of Patients With Relapsed or Refractory Multiple Myeloma (clinicaltrials.gov) - P2 | N=44 | Recruiting | Sponsor: Mayo Clinic | Not yet recruiting ➔ Recruiting

Enrollment open • Hematological Malignancies • Multiple Myeloma • Oncology

Brain FDG-PET Findings in late-onset parkinsonism after Anti-BCMA CAR T-Cell Therapy (SNMMI 2025) - " We describe an illustrative case of MNTs following anti-BCMA CAR T-cell therapy: A 77-year-old woman with high-risk multiple myeloma developed neuropsychiatric symptoms and parkinsonism on day 20 post-infusion of ciltacabtagene autoleucel... Anti-BCMA CAR T-cell therapy-related neurotoxicity, particularly MNTs, poses a unique clinical challenge with parkinsonism-like features and cognitive decline. Brain FDG-PET may play a critical role in the detection by revealing glucose metabolic changes, even when conventional imaging is normal. Patterns of cortical and basal ganglia glucose metabolism may provide valuable insights into the pathophysiology of MNTs and guide clinical management."

CAR T-Cell Therapy • FDG PET • IO biomarker • CNS Disorders • Cognitive Disorders • Hematological Malignancies • Movement Disorders • Multiple Myeloma • Oncology • Parkinson's Disease • Psychiatry

DIAGNOSIS, PREDICTORS AND OUTCOMES FOR IMMUNE EFFECTOR CELL ASSOCIATED ENTEROCOLITIS IN MULTIPLE MYELOMA PATIENTS RECEIVING CILTA-CEL (EHA 2025) - "Three pts (2/2 who received Vedolizumab, 1/3 who received Infliximab) achieved a durable response (≤ grade 1 diarrhea and not requiring TPN for >1 mo) within 5-16 mo; of these, one continues biologic therapy. One biologic-refractory pt was subsequently diagnosed with an enteropathic T-cell lymphoproliferative disorder (LPD) with a DNMT3A mutation and received cyclosporin, ruxolitinib and Upadacitinib sequentially with no durable response. One pt was treated with 2L high dose cyclophosphamide with no response after 1 mo... IEC-EC is associated with high morbidity and mortality. alkylator-based bridging, high-risk CAR-HEMATOTOX,peak ALC and delayed neurotoxicity, may be associated with increased risk of IEC-EC. Work up for IEC-EC should occur for any cases with ≥grade 2 diarrhea with stool analysis, imaging, ruling out infections, early EGD/colonscopy + biopsy and work-up for T-cell LPD."

Biomarker • Clinical • IO biomarker • CNS Disorders • Gastrointestinal Disorder • Hematological Malignancies • Infectious Disease • Movement Disorders • Multiple Myeloma • Oncology • Parkinson's Disease • DNMT3A