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

Hedge Fund Point72 Targets J&J Cancer Drug (Law Street Media) - "According to a new PoliScio Analytics analysis of early 2025 Freedom of Information Act requests, investment firm Point72 has launched a significant FOIA-driven investigation into Johnson & Johnson’s popular cancer drug Carvykti. According to Johnson & Johnson’s SEC filings and press releases, Carvykti has contributed significantly to the company’s recent financial performance and has benefitted hundreds of multiple myeloma patients. However, since the drug’s approval in 2022, the Food and Drug Administration’s adverse event reports attribute 159 deaths and 1,112 other serious cases to use of the drug. Hedge fund Point72, a leading alternative investment firm employing long/short equity and quantitative strategies, is seeking additional detail about those adverse event reports."

Commercial • Multiple Myeloma

Incidence and clinical predictors of cranial nerve palsies (CNPs) post ciltacabtagene-autoleucel (cilta-cel) in patients with relapsed or refractory multiple myeloma (RRMM). (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Comparative assessment of colitis-related adverse events in multiple myeloma patients treated with teclistamab, ciltacabtagene, and idecabtagene: Incidence, outcomes, and risk assessment. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Adverse events • Clinical • Gastroenterology • Gastrointestinal Disorder • Hematological Malignancies • Immunology • Multiple Myeloma • Oncology

Real world adverse events of ciltacabtagene autoleucel, a B-cell maturation antigen-directed chimeric antigen receptor T-cell therapy. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Adverse events • CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • Hematological Disorders • Hematological Malignancies • Oncology • Plasmacytoma

Comparative efficacy of idecabtagene vicleucel and ciltacabtagene autoleucel in relapsed/refractory multiple myeloma: Real-world analysis of overall survival and time to next treatment. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Real-world • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology

Investigating the association between peak post-infusion absolute lymphocyte count (ALC) and delayed toxicity in myeloma (MM) patients (pts) receiving cilta-cel. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Ciltacabtagene autoleucel (cilta-cel) vs standard of care (SOC) in patients (pts) with relapsed/refractory multiple myeloma (MM): CARTITUDE-4 survival subgroup analyses. (ASCO 2025) - P3 | "Clinical Trial Registration Number: NCT04181827 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Long-term (≥5 year) remission and survival after treatment with ciltacabtagene autoleucel (cilta-cel) in CARTITUDE-1 patients (pts) with relapsed/refractory multiple myeloma (RRMM). (ASCO 2025) - P1/2, P4 | "Clinical Trial Registration Number: NCT03548207, NCT05201781 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Overall Survival With Ciltacabtagene Autoleucel Versus Standard of Care in Lenalidomide-Refractory Multiple Myeloma: CARTITUDE-4 Update (BSH 2025) - No abstract available

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Cilta-Cel Emerges as a SOC in Lenalidomide-Refractory Multiple Myeloma (OncLive) - P3 | N=419 | CARTITUDE-4 (NCT04181827) | Sponsor: Janssen Research & Development, LLC | "During the 51st Annual EBMT Meeting, Mateos presented updated data from the phase 3 CARTITUDE-4 trial...which compared cilta-cel with SOC therapies in patients with lenalidomide-refractory multiple myeloma who received 1 to 3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD).1 At a median follow-up of 33.6 months (range, 0.1-45.0), patients who received the CAR T-cell therapy (n = 208) experienced a 45% reduction in the risk of death compared with those who received SOC agents (n = 211; HR, 0.55; 95% CI, 0.39-0.79; P = .0009). The 30-month overall survival (OS) rates were 76.4% and 63.8%, respectively....At this follow-up, no new safety signals were reported."

P3 data • Multiple Myeloma

CAR-T for multiple myeloma: practice pearls. (PubMed, Bone Marrow Transplant) - "The CAR-T cell products ciltacabtagene autoleucel and idecabtagene vicleucel have transformed the management of patients with multiple myeloma. Here, we present a practical guide highlighting clinical pearls on the incorporation of CAR-T into clinical practice. Topics addressed include expected outcomes, recommendations for referral timing, bridging therapy, treatment complications, therapeutic sequencing, and management of relapse."

Journal • Review • Hematological Malignancies • Multiple Myeloma • Oncology

Long-term Effects of Ciltacabtagene Autoleucel on Patient-Reported Outcomes and Time to Next Anti-myeloma Therapy vs Standard of Care in the CARTITUDE-4 Trial of Patients With Lenalidomide-Refractory Multiple Myeloma (ONS 2025) - "At the MFU of 34 months, cilta-cel was associated with significantly longer TTW of symptoms and impact on MySIm-Q versus SOC (Figure). By 30 months after randomization, 77% and 83% of cilta-cel–treated patients had not experienced worsening of symptoms or functional impacts, respectively, compared to 63% and 69% of the SOC group. Improvements from baseline in MySIm-Q symptom and impact scores were greater with cilta-cel versus SOC."

Clinical • Patient reported outcomes • Hematological Malignancies • Multiple Myeloma • Oncology

Effectiveness of Bridging Therapy Corresponds to Improved Outcomes After Receiving CAR-T Therapy: Phase 3 CARTITUDE-4 Study of Patients With Relapsed, Lenalidomide-Refractory Multiple Myeloma (ONS 2025) - P3 | "Bridging therapy included physician's choice of either daratumumab, pomalidomide, and dexamethasone (DPd) or pomalidomide, bortezomib, and dexamethasone (PVd). Of 176 patients who received cilta-cel as study treatment, 158 received DPd and 18 received PVd as bridging therapy. Most patients had ≥25% reduction in tumor burden in response to bridging therapy (Figure). At the 15.9-month median follow-up, median PFS (95% confidence interval) was not reached (not estimable [NE]-NE) in the ≥25% decrease group and 19.2 months (15.8 months-NE) in the <25% decrease group."

Clinical • IO biomarker • P3 data • Hematological Malignancies • Multiple Myeloma • Oncology

Incidence of Infection and Immune Recovery in the CARTITUDE-4 Trial of Ciltacabtagene Autoleucel Versus Standard of Care for Treatment of Multiple Myeloma (ONS 2025) - P3 | "Significance & Background: Ciltacabtagene autoleucel (cilta-cel) significantly improved progression-free survival versus standard of care (SOC; hazard ratio [HR], 0.26; P<0.0001) in patients with lenalidomide-refractory multiple myeloma (MM) after 1-3 prior lines of therapy in the phase 3 CARTITUDE-4 trial (NCT04181827) at the 15.9-month median follow-up (MFU)...Interventions: Patients were randomized to a single infusion of cilta-cel or SOC (daratumumab-pomalidomide-dexamethasone/pomalidomide-bortezomib-dexamethasone)... Overall, 128 of 208 cilta-cel–treated patients (61.5%) and 157 of 208 SOC-treated patients (75.5%) had treatment-emergent (TE) infections of any grade; grade ≥3 TE infections occurred in 57 patients (27.4%) and 56 patients (26.9%) in the cilta-cel versus SOC groups, respectively. Rates of grade ≥3 TE infections in the cilta-cel group were highest within the first 6 months and decreased thereafter (Figure). TE fatal infections occurred in 9..."

Hematological Malignancies • Multiple Myeloma • Oncology

Long-term Efficacy and Safety of Ciltacabtagene Autoleucel Versus Standard of Care for Treatment of Lenalidomide-Refractory Multiple Myeloma in the CARTITUDE-4 Trial (ONS 2025) - P3 | "Interventions: Patients in CARTITUDE-4 were randomly assigned to a single infusion of cilta-cel or SOC (pomalidomide-bortezomib-dexamethasone [PVd]/daratumumab-pomalidomide-dexamethasone [DPd]). Overall, 419 patients were randomized (intent-to-treat population; cilta-cel, n=208; SOC, n=211). Median OS was not reached (NR) with cilta-cel or SOC (HR, 0.55 [protocol-specified weighted analysis]; 95% confidence interval, 0.39-0.79; P=0.0009); 30-month OS rates were 76% and 64%, respectively (Table). OS benefit was generally maintained across prespecified subgroups (eg, 1 vs 2-3 prior lines of therapy, cytogenetic high-risk disease, refractory status)."

Clinical • Hematological Malignancies • Multiple Myeloma • Oncology

Absolute lymphocyte count after CAR-T therapy has different kinetics and predicts better outcomes in B-cell malignancies (AACR 2025) - "Introduction: Chimeric antigen receptor (CAR) T-cell therapy targeting CD19 and BCMA antigens are now a valuable option for patients with relapsed or refractory (R/R) B-Cell malignancies Commercially available products consist of an antigen binding domain against CD19 or BCMA and one of two main co-stimulatory molecules, CD28 (Axi-Cel , Brexu-Cel ) and 41-BB (Tisa-Cel, Liso-Cel, Cilta-cel, and Ide-cel). ALCmax was associated with better PFS in DLBCL patients treated with both types of CD19 products and in MM patients treated with BCMA-41-BB CAR-T products. This data suggests that ALCmax is a good marker for response to CAR-T therapy and encourages better understanding of the factors influencing ALC levels between the CAR-T products and disease subtypes."

IO biomarker • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Distinct expansion, phenotype, function, and toxicity of cilta-cel vs. ide-cel CAR T cells in the real world (AACR 2025) - "This first report of in-depth, comparative patient biomonitoring following real-world cilta-cel or ide-cel therapy highlights intrinsic biological differences between these BCMA-targeting CAR T products, potentially explaining differences in clinical activity and toxicity. Our findings may guide the optimization of cellular immunotherapy strategies in myeloma patients."

CAR T-Cell Therapy • Clinical • IO biomarker • Real-world • Real-world evidence • Hematological Malignancies • Multiple Myeloma • Oncology • CD27 • CD4

LEGEND BIOTECH ANNOUNCES PRELIMINARY SALES FOR CARVYKTI FOR THE QUARTER ENDED 31 MARCH 2025 (HKEXnews) - "Legend Biotech Corporation...announced that CARVYKTI generated approximately US$369 million in net trade sales during the quarter ended March 31, 2025. This is pursuant to the Collaboration and License Agreement dated December 21, 2017 between Legend Biotech and Janssen Biotech, Inc. ('Janssen'). The net trade sales figure is based on information provided to Legend Biotech by Janssen, and neither Legend Biotech nor the Company have independently verified the accuracy of such sales figure."

Sales • Multiple Myeloma

Economic Impact of Elranatamab for Treatment of Patients with Relapsed or Refractory Multiple Myeloma. (PubMed, Clinicoecon Outcomes Res) - "Total cost of care per month of median PFS over one year was $19,642 with elranatamab, talquetamab ($33,391), teclistamab ($37,791), selinexor plus dexamethasone ($48,784), physician's choice of treatment ($65,886), idecabtagene vicleucel ($78,361), and ciltacabtagene autoleucel ($17,640). Elranatamab for RRMM is projected to result in a minimal to small budget impact over 3 years and good economic value with lower cost of care per month of PFS compared with other available RRMM treatments except for ciltacabtagene autoleucel."

HEOR • Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Current Treatment Strategies for Multiple Myeloma at First Relapse. (PubMed, J Clin Med) - "Cilta-cel, a chimeric antigen receptor T-cell construct, has emerged as the most promising therapeutic option at first relapse, resulting in long-term remissions with a significant treatment-free interval...Triplet regimens based on carfilzomib, pomalidomide or selinexor, remain the cornerstone of treatment at first relapse, whereas the optimal combination is based on refractoriness to prior drugs, especially anti-CD38 monoclonal antibodies and lenalidomide, and patient comorbidities. With the rapidly expanding therapeutic landscape, clinicians face increasing complexity in selecting the most appropriate regimens for individual patients. This review aims to guide clinicians through these evolving options by consolidating evidence-based strategies and highlighting emerging therapies, ensuring a personalized approach to managing first-relapse MM."

Journal • Review • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Multiple Myeloma • Oncology • Transplantation

“Update of sections 4.8, and 5.1 of the SmPC in order to update the list of adverse drug reactions (ADRs), and update clinical efficacy and safety information based on second interim analysis from study 68284528MMY3002 (CARTITUDE-4)…In addition, the MAH took the opportunity to update the list of local representatives in the Package Leaflet” (European Medicines Agency) - Pharmacovigilance Risk Assessment Committee (PRAC) Minutes of meeting on 10 – 13 Feb 2025

PRAC • Hematological Malignancies • Multiple Myeloma • Oncology

ANALYSIS OF MAJOR ADVERSE CARDIAC EVENTS (MACE) AND SURVIVAL OUTCOMES BY CAR-T SUBTYPE: CD-19 VERSUS BCMA DIRECTED THERAPY IN LYMPHOMA AND MULTIPLE MYELOMA PATIENTS (EBMT 2025) - " A single-center retrospective comparative cohort study was performed in R/R MM and B-cell lymphoma patients treated with FDA approved CD19-directed (axicabtagene ciloleucel/lisocabtagene maraleucel) and BCMA-directed CAR-T cells (idecabtagene vicleucel/ciltacabtagene autoleucel). Cardiovascular toxicity as measured by MACE was present in approximately 50% of patients with arrythmias as the most frequent event. Though numerically higher for CD19 CAR-T there was no significant difference between CAR-T cohorts per targeted antigens. Additionally, no difference was found in cardiovascular or all-cause readmissions, CRS incidence, or Tocilizumab utilization.Conversely, BCMA CAR-T therapy demonstrated a higher risk of earlier mortality in comparison to CD19 CAR-T therapy and a more profound decrease of fibrinogen levels during treatment.Further research is warranted to explore the relationship between CAR-T therapy and cardiovascular toxicities including the underlying..."

Adverse events • Clinical • IO biomarker • Acute Coronary Syndrome • B Cell Lymphoma • Cardiovascular • Congestive Heart Failure • Heart Failure • Hematological Malignancies • Lymphoma • Multiple Myeloma • Myocardial Infarction • Non-Hodgkin’s Lymphoma • Oncology • CRP

LYMPHODEPLETION WITH SINGLE AGENT BENDAMUSTINE PRIOR TO CAR T-CELL THERAPY IN PATIENTS WITH IMPAIRED RENAL FUNCTION (EBMT 2025) - "Background: Chimeric antigen receptor T-cell therapy (CART) leads to high rates of remission in patients with aggressive lymphomas (NHL) and multiple myeloma (MM) and is commonly applied following lymphodepletion (LD) with fludarabine and cyclophosphamide... 10 patients (50% female) received bendamustine for LD prior to CART in real-world setting (ciltacabtagene-autoleucel N=7, lisocabtagene maraleucel N=1, brexucabtagene autoleucel N=1, axicabtagene ciloleucel N=1)... In our cohort, 2/7 patients with in-specification CART products showed no expansion of CAR T-cells. In contrast, 3/3 patients with OOS products had sufficient expansion of CAR T-cells and responded to treatment. Further studies are warranted to determine the role bendamustine in LD prior to CART patients with chronic kidney injury."

CAR T-Cell Therapy • Clinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Nephrology • Oncology • Pneumonia • Renal Disease • Respiratory Diseases • IFNG

LYMPHODEPLETION WITH SINGLE AGENT BENDAMUSTINE PRIOR TO CAR T-CELL THERAPY IN PATIENTS WITH IMPAIRED RENAL FUNCTION (EBMT 2025) - "Background: Chimeric antigen receptor T-cell therapy (CART) leads to high rates of remission in patients with aggressive lymphomas (NHL) and multiple myeloma (MM) and is commonly applied following lymphodepletion (LD) with fludarabine and cyclophosphamide... 10 patients (50% female) received bendamustine for LD prior to CART in real-world setting (ciltacabtagene-autoleucel N=7, lisocabtagene maraleucel N=1, brexucabtagene autoleucel N=1, axicabtagene ciloleucel N=1)... In our cohort, 2/7 patients with in-specification CART products showed no expansion of CAR T-cells. In contrast, 3/3 patients with OOS products had sufficient expansion of CAR T-cells and responded to treatment. Further studies are warranted to determine the role bendamustine in LD prior to CART patients with chronic kidney injury."

CAR T-Cell Therapy • Clinical • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Nephrology • Oncology • Pneumonia • Renal Disease • Respiratory Diseases • IFNG

Advancing Equity in CAR T-Cell Therapy: An Analysis of Health Technology Assessments by Canada's Drug Agency and the National Institute for Health and Care Excellence (ISPOR 2025) - "This review examines if and how health technology assessments (HTAs) by Canada's Drug Agency (CDA) and the National Institute for Health and Care Excellence (NICE) consider equity in evaluating CAR T-cell therapies. HTA reports from CDA and NICE for six CAR T-cell therapies (Abecma, Breyanzi, Carvykti, Kymriah, Tecartus, Yescarta) were reviewed by two researchers for equity considerations related to access disparities, capacity, socioeconomic determinants, and related clinical and economic evidence. This review identified that DEI considerations related to CAR T-cell therapy access like patient costs and geographical barriers were not routinely supported by evidence in CDA and NICE submissions. Evidence generation challenges in CAR-T therapy may inadvertently deprioritize equity concerns. Recent commitments to equity from HTA bodies offer opportunities to ensure fair access to novel, high-cost therapies."

CAR T-Cell Therapy • Reimbursement • US reimbursement • Hematological Disorders • Hematological Malignancies • Oncology