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

Gene regulatory elements determine efficacy of BCMA-targeted CAR-T cell products. (PubMed, J Immunother Cancer) - "The advantage attributed to cilta-cel's dual VHH binder was lost when expressed under MND-WPRE and, conversely, ide-cel's scFv binder achieved better antitumor activity when expressed under EF1α+WPRE than under MND-WPRE The efficacy difference between our CAR constructs in xenograft models therefore tracked with the choice of regulatory elements driving CAR expression independently of the binder. It may be better to choose gene regulatory elements based on the CAR-T cell function they confer rather than on expression strength alone."

IO biomarker • Journal • Gene Therapies • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology • Sarcoma • Solid Tumor • CD69 • NFATC1

Phase II trial of belantamab mafodotin, carfilzomib, pomalidomide, and dexamethasone in multiple myeloma following BCMA CAR T-cell therapy (ASH 2025) - "Four patients received cilta-cel, five patients receivedinvestigational BCMA CAR T-cell therapies, and two patients received both; all patients responded to eachCAR T administered.The ORR was 9/11 (82%) meeting the statistical threshold for efficacy. Bela-KPd utilizing less frequent dosing of Bela led to a favorable efficacy and safety profile,even among patients with prior BCMA CAR T-cell therapy and carfilzomib and pomalidomiderefractoriness. Bela-KPd is a promising regimen for patients following relapse after BCMA CAR T-celltherapy.Partial funding and study drug were provided by GSK and Amgen (ClinicalTrials.gov identifierNCT05789303)."

CAR T-Cell Therapy • IO biomarker • P2 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Ophthalmology • Thrombocytopenia

Ciltacabtagene autoleucel vs standard of care in patients with functional high-risk multiple myeloma: CARTITUDE-4 subgroup analysis. (ASCO 2024) - P3 | "In CARTITUDE-4, a single ciltacabtagene autoleucel (cilta-cel) infusion significantly improved progression-free survival (PFS) vs established standard of care (SC; hazard ratio [HR], 0.26 [95% CI, 0.18–0.38]; P<.0001) in patients (pts) with lenalidomide (len)-refractory MM after 1–3 prior lines of treatment (tx; LOT). In pts with len-refractory FHR MM after 1 prior LOT, cilta-cel improved outcomes vs SC and had a safety profile consistent with the known mechanism of action of CAR-T tx, suggesting cilta-cel may overcome the poor prognosis associated with FHR MM."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Patient-Reported Outcomes in the Phase 3 CARTITUDE-4 Study of Ciltacabtagene Autoleucel Vs Standard of Care in Patients with Lenalidomide-Refractory Multiple Myeloma after 1–3 Lines of Therapy (ASH 2023) - P3 | "Introduction: The phase 3 CARTITUDE-4 trial (NCT04181827) in patients with multiple myeloma (MM) after 1–3 lines of therapy compared ciltacabtagene autoleucel (cilta-cel) with standard of care (SOC; pomalidomide, bortezomib, and dexamethasone or daratumumab, pomalidomide, and dexamethasone). Patients with lenalidomide-refractory MM who had 1–3 prior lines of therapy demonstrated clinically meaningful improvements in health-related quality of life and meaningful reductions in disease-specific symptoms on multiple PRO endpoints after a single cilta-cel infusion. Improvements in health-related quality of life were numerically greater with cilta-cel than with continuously administered SOC treatments across all scales. With previously reported data showing that cilta-cel significantly improves PFS, response rate, and depth of response, these results strengthen the potential for cilta-cel to be a new SOC for patients with lenalidomide-refractory MM after first relapse."

Clinical • P3 data • Patient reported outcomes • Fatigue • Hematological Malignancies • Multiple Myeloma • Oncology

Long-term progression-free survival benefit with ciltacabtagene autoleucel in standard-risk relapsed / refractory multiple myeloma (ASH 2025) - P1/2, P3 | "Introduction: The CARTITUDE-4 study (NCT04181827), which enrolled patients with lenalidomide-refractory multiple myeloma (MM) after 1–3 prior lines of therapy (pLOT), demonstrated a significantbenefit of ciltacabtagene autoleucel (cilta-cel) over established triplet regimens...Here, we report outcomes inpatients with standard-risk cytogenetics from the intent-to-treat and as-treated populations inCARTITUDE-4. In CARTITUDE-4, patients randomized to the cilta-cel arm underwent apheresis and bridgingtreatment with either pomalidomide, bortezomib, and dexamethasone (PVd) or daratumumab,pomalidomide, and dexamethasone (DPd), followed by lymphodepletion therapy with cyclophosphamideand fludarabine, and then a single cilta-cel infusion... The PFS rate at 2.5 years for patients with standard-risk RRMM was higher in CARTITUDE-4compared with CARTITUDE-1, supporting the use of cilta-cel as early as second line in the treatmentcourse. In CARTITUDE-4 (as-treated..."

Hematological Malignancies • Multiple Myeloma

Ciltacabtagene Autoleucel (Cilta-cel) Vs Standard of Care (SoC) in Patients with Lenalidomide (Len)-Refractory Multiple Myeloma (MM) after 1–3 Lines of Therapy: Minimal Residual Disease (MRD) Negativity in the Phase 3 Cartitude-4 Trial (ASH 2024) - P3 | "Pts were assigned 1 : 1 to cilta-cel or SoC (pomalidomide, bortezomib, and dexamethasone [PVd]/daratumumab, pomalidomide, and dexamethasone [DPd]). These data further underscore the benefit of cilta-cel, which led to significant >3-fold increases vs SoC in rates of MRD-negative ≥CR at any time and at mo 12, and sustained MRD negativity. Our MRD data demonstrate higher rates of deep and sustained MRD negativity achieved with cilta-cel vs SoC in tx of len-refractory MM as early as first relapse."

Clinical • Minimal residual disease • P3 data • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology

[PRE-RECORD] Updated Results of Cartitude-2: Ciltacabtagene Autoleucel (cilta-cel), a B-Cell Maturation Antigen (BCMA)–Directed Chimeric Antigen Receptor T Cell (CAR-T) Therapy, in Lenalidomide-Refractory Patients with Progressive Multiple Myeloma (MM) after 1–3 Prior Lines of Therapy (TCT-ASTCT-CIBMTR 2022) - P2 | "A single cilta-cel infusion (target dose 0.75×10 6 CAR+ viable T cells/kg) was given 5–7 d after start of lymphodepletion (cyclophosphamide [300 mg/m 2 ] and fludarabine [30 mg/m 2 ] for 3 d)...All pts were exposed to a PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab... A single cilta-cel infusion led to early and deep responses in pts with MM who had 1–3 prior LOT and were lenalidomide-refractory. No movement and neurocognitive TEAEs occurred, suggesting success of monitoring and pt management strategies implemented across phase 2/3 studies in the CARTITUDE program."

CAR T-Cell Therapy • Clinical • Anemia • CNS Disorders • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukopenia • Multiple Myeloma • Neutropenia • Novel Coronavirus Disease • Oncology • Thrombocytopenia

Pharmacokinetic and correlative analysis of ciltacabtagene autoleucel in patients with lenalidomide-refractory multiple myeloma in the CARTITUDE-4 trial (IMW 2023) - P3 | "Pts randomized to cilta-cel underwent apheresis, received physician's choice of pomalidomide-based bridging treatment, and then 1 cilta-cel infusion (target dose 0.75×10⁶ CAR+ viable T cells/kg) 5–7 d after lymphodepletion. CAR transgene and cellular levels in CARTITUDE-4 were concordant with observations in CARTITUDE-1 and showed similar expansion and persistence profiles. Based on the samples available at data cut-off, sBCMA levels and proportion of BCMA+ MM cells return to levels at or above baseline at time of relapse, without reappearance or re-expansion of CD3+CAR+ cells in blood. Study follow-up is ongoing, and more samples may be available with additional follow-up."

Clinical • IO biomarker • PK/PD data • Hematological Malignancies • Multiple Myeloma • Oncology

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

Long-Term (=5-Year) Remission and Survival with Ciltacabtagene Autoleucel (Cilta-Cel) in Relapsed/Refractory Multiple Myeloma (RRMM) with 1-3 Prior Lines of Therapy: CARTITUDE 2 Cohort a (IMS 2026) - P2, P4 | "Introduction: CARTITUDE‑1 demonstrated that a single cilta‑cel infusion can achieve deep and durable responses in heavily pretreated RRMM, with 33% of patients (pt) alive and progression-free at 5 years, suggesting curative potential. Half (10/20 [50.0%]) of the pts treated with a single cilta‑cel infusion in earlier-line RRMM (CARTITUDE-2 cohort A; 1-3 prior lines of therapy and lenalidomide-refractory) had sustained remissions of ≥5 years. These results build on the long-term outcomes from CARTITUDE‑1 and suggest that earlier use of cilta‑cel may be associated with a higher likelihood of achieving 5-year remissions."

CAR T-Cell Therapy • Clinical • Acute Myelogenous Leukemia • Breast Cancer • Hematological Malignancies • Infectious Disease • Leukemia • Multiple Myeloma • Pneumonia • Respiratory Diseases • Septic Shock • Solid Tumor • CD4

Cost-Effectiveness of Cilta-cel in Lenalidomide-Refractory Multiple Myeloma: An Analysis of the CARTITUDE-4 Trial. (PubMed, Value Health) - "Relative to standard therapy, cilta-cel is projected to exhibit an economic absolute cost-effectiveness advantage in the treatment of lenalidomide-refractory multiple myeloma."

HEOR • Journal • Hematological Malignancies • Multiple Myeloma • Oncology

First phase 3 results from CARTITUDE-4: Cilta-cel versus standard of care (PVd or DPd) in lenalidomide-refractory multiple myeloma. (ASCO 2023) - P3 | "Background: CARTITUDE-4 is a global, phase 3, randomized, controlled trial (NCT04181827) of ciltacabtagene autoleucel (cilta-cel), a dual-binding, BCMA-targeting CAR-T cell therapy, vs standard of care (SOC; pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]) in lenalidomide (len)-refractory patients (pts). A single cilta-cel infusion significantly improved PFS vs SOC in len-refractory pts with 1–3 prior LOT, with a favorable benefit/risk profile across pt populations. The 74% reduction in progression/death and high rates of CR and MRD negativity highlight the potential for cilta-cel to become a key therapy for pts with MM after first relapse. Clinical trial information: NCT04181827."

Late-breaking abstract • P3 data • Hematological Disorders • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Oncology

Effectiveness of bridging therapy corresponds to improved outcomes after ciltacabtagene autoleucel: Phase 3 CARTITUDE-4 study of patients with relapsed, lenalidomide-refractory multiple myeloma (ASH 2025) - "Patients in the cilta-cel arm underwent apheresis, received at least 1 cycle of bridging therapy(investigator's choice) with either pomalidomide, bortezomib, and dexamethasone (PVd) ordaratumumab, pomalidomide, and dexamethasone (DPd), lymphodepletion (cyclophosphamide andfludarabine), and then a single cilta-cel infusion 5–7 days after the start of lymphodepletion. In patients from CARTITUDE-4, better response to bridging therapy correlated with longerPFS and OS. No MNTs were observed in patients who achieved PR or greater following bridging therapy.Patients with poorer responses to bridging therapy were more likely to develop fatal infections,prolonged thrombocytopenia and neutropenia, and had higher rates of non-relapse mortality followingcilta-cel infusion. These data emphasize the importance of optimizing bridging therapy for diseasecontrol prior to receiving cilta-cel."

Clinical • P3 data • Hematological Malignancies • Infectious Disease • Multiple Myeloma • Neutropenia • Thrombocytopenia

Dasatinib and Quercetin in Patients with Relapsed, Refractory Multiple Myeloma Receiving CAR-T Therapy: First Report from the Safety Run-in of the Phase II DART Trial (IMS 2026) - P2 | "In the safety run-in of the DART trial, D+Q with cilta-cel was feasible and showed a safety profile consistent with cilta-cel alone, and no new signals associated with D+Q. Updated clinical and correlative results including additional TIS analysis in bone marrow biopsy will be reported."

CAR T-Cell Therapy • Clinical • P2 data • Cardiovascular • Hematological Malignancies • Hypertension • Infectious Disease • Multiple Myeloma • Neutropenia • Pneumonia • Respiratory Diseases • B3GAT1 • CD14 • KLRG1

First Results of a Noninterventional, Prospective, Postauthorization Safety Study (PASS) of Ciltacabtagene Autoleucel (Cilta-Cel) in Patients (Pts) with Relapsed/Refractory Multiple Myeloma (RRMM) (IMS 2026) - "80 (75.5%) pts had bridging therapy (BT; mBT 6.4 wk); common BT agents were dexamethasone (67.5%), carfilzomib (42.5%), daratumumab (33.8%), talquetamab (26.3%), and pomalidomide (21.3%). Initial results of this RW PASS demonstrate cilta-cel outcomes in Europe and Brazil were comparable with clinical trial result s. Safety was consistent with known cilta-cel safety profile. Half of pts received cilta-cel after 1–2 pLOT, supporting using cilta-cel as standard of care for RRMM in early LOT. Acknowledgments: This study was funded by Johnson & Johnson, and Legend Biotech USA Inc."

Clinical • CNS Disorders • Gastric Cancer • Genetic Disorders • Hematological Malignancies • Infectious Disease • Movement Disorders • Multiple Myeloma • Neutropenia • Non-melanoma Skin Cancer • Parkinson's Disease • Skin Cancer • Solid Tumor

Single-Cell Phylogenetic Dynamics During Immunotherapy and at Minimal Residual Disease Timepoints in Multiple Myeloma (IMS 2026) - "To identify these cells, we used longitudinal single-cell whole-genome sequencing (scWGS) to characterize tumor cells, including rare MRD cells, from patients treated with quadruplet therapy (Daratumumab, Lenalidomide, Bortezomib, Dexamethasone; DRVd), anti-BCMA-directed T-cell-redirecting therapy (Teclistamab), or anti-BCMA CAR-T cell therapy (Cilta-cel). Longitudinal scWGS reveals that persistent tumor cells during immunotherapy and at MRD timepoints arise from genomically mature residual clones that continue to evolve under therapeutic pressure. scWGS enables detection of resistant subclones and target-antigen alterations below the sensitivity of bulk sequencing, providing insight into mechanisms of resistance and relapse evolution in MM."

IO biomarker • Minimal residual disease • Residual disease • Hematological Malignancies • Multiple Myeloma • Plasmacytoma • CD38 • SDC1 • TNFRSF17 • TP53

Quality-adjusted survival analysis of neurologic events with ciltacabtagene autoleucel (Cilta-cel) vs standard of care (SOC) in patients (Pts) with lenalidomide-refractory multiple myeloma (MM) who received 1–3 prior lines of therapy (LOT): Cartitude-4 trial population (Pop) (ASH 2025) - P3 | "Given that neurologic AEs, though infrequent, are a recognized consideration with CAR-T therapies suchas cilta-cel, this focused Q-TWiST analysis evaluated the specific impact of these events on quality-adjusted survival. In both base case and sensitivity scenarios, pts treated with cilta-cel experiencedstatistically significant and clinically meaningful gains in quality-adjusted survival vs SOC, with gainsexceeding the 10–15% threshold generally considered important in oncology. In the ITT pop, a significantimprovement was observed in time without neurologic AEs for cilta-cel vs SOC."

Clinical • CNS Disorders • Hematological Malignancies • Inflammation • Mental Retardation • Multiple Myeloma

Ciltacabtagene Autoleucel (Cilta-cel) Vs Standard of Care (SoC) in Patients with Lenalidomide (Len)-Refractory Multiple Myeloma (MM) after 1–3 Lines of Therapy: Minimal Residual Disease (MRD) Negativity in the Phase 3 Cartitude-4 Trial (TCT-ASTCT-CIBMTR 2025) - P3 | " Pts were assigned to cilta-cel or SoC (pomalidomide, bortezomib, dexamethasone [PVd]/daratumumab, pomalidomide, dexamethasone [DPd]). At 33.6-mo MFU in CARTITUDE-4, cilta-cel vs SoC significantly increased overall MRD-negativity rates, with pts achieving MRD negativity rapidly post cilta-cel. These data underscore the benefit of cilta-cel, which led to significant increases vs SoC in rates of MRD-negative ≥CR and sustained MRD negativity and demonstrate higher rates of deep and sustained MRD negativity achieved with cilta-cel vs SoC in tx of len-refractory MM as early as first relapse."

Clinical • Minimal residual disease • P3 data • Residual disease • Hematological Malignancies • Multiple Myeloma • Oncology

Could Less Be More? Reconsidering Immunosuppressive Escalation in Refractory Immune Effector Cell-Associated Enterocolitis Complicated by Recurrent C. difficile Infection (ACG 2026) - "Case Description/ A 73-year-old male with multiple myeloma (MM) refractory to several lines of therapy underwent CAR-T infusion with ciltacabtagene autoleucel, developing biopsy-proven disease progression with infiltrative extramedullary disease of the GI tract...difficile PCR returned positive with negative toxin, creating diagnostic uncertainty in the setting of suspected IEC-AE; fidaxomicin was initiated...Diarrhea worsened despite two doses each of cyclophosphamide and vedolizumab...Concurrently, vancomycin was initiated for repeat C. difficile infection and valganciclovir for cytomegalovirus viremia. Ruxolitinib was given for refractory IEC-AE alongside fludarabine for the recurrent and progressive MM involving the GI tract...(A) Upper endoscopy demonstrating diffuse nodular mucosa involving the duodenal bulb and 1st and 2nd portions of the duodenum. (B) Colonoscopy showing grossly normal ascending, transverse, and descending colon despite biopsy-confirmed IEC-AE."

Cytomegalovirus Infection • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Immunology • Infectious Disease • Inflammatory Bowel Disease • Multiple Myeloma

Overall Survival (OS) With Ciltacabtagene Autoleucel (Cilta-cel) Versus Standard of Care (SoC) in Lenalidomide (Len)-Refractory Multiple Myeloma (MM): Phase 3 CARTITUDE-4 Study Update (IMW 2024) - " Pts were randomized to cilta-cel or SoC (pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]). At ~3 years of follow-up, cilta-cel significantly extended OS, reducing the risk of death vs SoC by 45%, and significantly improved quality-of-life measures vs SoC. Collectively, these data continue to support the overall benefit-risk profile of cilta-cel vs SoC in pts with len-refractory MM as early as after first relapse."

Clinical • Late-breaking abstract • P3 data • Acute Myelogenous Leukemia • Epstein-Barr Virus Infections • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Dasatinib for Cranial Nerve Palsy Following Cilta-Cel (IMS 2026) - "Dasatinib represents a potentially novel therapeutic option for the management of certain CAR-T related toxicities. We treated 8 patients who experienced Cilta-cel related CNPs with a Dasatinib containing approach. The timing of initial improvement observed gives potential support for dasatinib having CAR T activity modifying effect while high rate of recurrence after initial improvement indicates that dasatinib related modification appeared short lived."

Hematological Malignancies • LCK

BCMA CAR-T induces complete and durable remission in refractory plasmablastic lymphoma. (PubMed, J Immunother Cancer) - P1b | "Chimeric antigen receptor T-cell (CAR-T) therapy directed against BCMA has shown efficacy for the treatment of heavily pretreated MM with low rates of grades 3 and 4 cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) in a phase Ib/II trial (A Study of JNJ-68284528, a CAR-T Directed Against BCMA in Participants With Relapsed or Refractory Multiple Myeloma (CARTITUDE-1), NCT03548207)...The patient developed rapidly advancing disease despite withdrawal of immunosuppression, treatment with etoposide, ibrutinib, and daratumumab, prompting consideration of BCMA CAR-T (under emergency investigational new drug (eIND))...BCMA CAR-T expansion was detected in vivo, peaking on day 15. The patient remains in CR for more than a year post CAR-T therapy, supporting consideration of immunotherapy for future patients with refractory PBL, a disease with few treatment options."

Journal • Acute Lymphocytic Leukemia • B Acute Lymphoblastic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • Pediatrics • Transplantation

OVERALL SURVIVAL (OS) WITH CILTACABTAGENE AUTOLEUCEL (CILTA-CEL) VERSUS STANDARD OF CARE (SOC) IN LENALIDOMIDE (LEN)-REFRACTORY MULTIPLE MYELOMA (MM): PHASE 3 CARTITUDE-4 STUDY UPDATE (EBMT 2025) - P3 | " Pts were randomized to cilta-cel or SoC (pomalidomide, bortezomib, and dexamethasone [PVd] or daratumumab, pomalidomide, and dexamethasone [DPd]). At ~3 years of follow-up, cilta-cel significantly extended OS, reducing the risk of death vs SoC by 45%, and significantly improved quality-of-life measures vs SoC. Collectively, these data continue to support the overall benefit-risk profile of cilta-cel vs SoC in pts with len-refractory MM as early as after first relapse. Clinical Trial Registry: https://www.clinicaltrials.gov/study/NCT04181827"

Clinical • P3 data • Acute Myelogenous Leukemia • Epstein-Barr Virus Infections • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Lymphoma • Multiple Myeloma • Myelodysplastic Syndrome • Oncology • Peripheral T-cell Lymphoma • T Cell Non-Hodgkin Lymphoma

Patient-reported outcomes following ciltacabtagene autoleucel or standard of care in patients with lenalidomide-refractory multiple myeloma (CARTITUDE-4): results from a randomised, open-label, phase 3 trial. (PubMed, Lancet Haematol) - P3 | "Health-related QoL improvements and delayed symptom worsening support cilta-cel's clinical efficacy in lenalidomide-refractory disease."

Clinical • Journal • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

Cost-Effective Analysis of Teclistamab and Daratumumab vs Ciltacabtagene Autoleucel in Relapsed Multiple Myeloma (SOHO 2026) - "Despite superior modeled PFS, tec/dara is not cost-effective compared with cilta-cel at current pricing in relapsed/refractory MM. Response-adapted, fixed-duration treatment strategies merit further evaluation to reconcile the regimen's clinical benefit with its cumulative economic burden, particularly as the relapsed/refractory MM landscape evolves toward balancing accessibility of bispecific antibodies against the cost-efficiency of one-time cellular therapies. BCMA: B-cell maturation antigen; CAR-T: chimeric antigen receptor T-cell; CI: confidence interval; HR: hazard ratio; ICER: incremental cost-effectiveness ratio; MM: multiple myeloma; PFS: profession-free survival; QALY: quality-adjusted life-year; WTP: willingness-to-pay."

Cost effectiveness • HEOR • Hematological Malignancies • Multiple Myeloma • Oncology