Yescarta (axicabtagene ciloleucel) / Cabaret Biotech, National Cancer Institute, Gilead, Fosun Kite - LARVOL DELTA

Diffusion and Launch Sequencing of Cell and Gene Therapies across the USA, Europe, Canada and Australia (ISPOR 2025) - "Only four products had positive HTA recommendations in all screened markets: Zolgensma, Luxturna, and Yescarta and Tecartus. Low rates of marketing authorisation and HTA approval have contributed to a fragmented access landscape for CGTs. While large firms may be better equipped to launch these technologies globally, high prices, uncertainties in clinical evidence, and technical complexities in administering therapies present continued barriers to uptake."

Gene therapy • Gene Therapies

Cost-Effectiveness Analysis of Axicabtagene Ciloleucel as a Second-Line Treatment for Diffuse Large B-Cell Lymphoma in China (ISPOR 2025) - "From the Chinese health system perspective, Axi-cel is not cost-effective as second-line therapy for DLBCL. While considering the productivity value of gene therapy drugs, from the societal perspective, the economic evaluation of Axi-cel has shown a positive result. The result suggests that access to innovative high-value medicine, represented by gene therapies, should consider a broader range of value dimensions."

Clinical • Cost effectiveness • HEOR • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Gene Therapies • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

An Economic Model to Estimate Costs of Adverse Events in Patients Treated With Lisocabtagene Maraleucel (liso-cel), Axicabtagene Ciloleucel (axi-cel), or Tisagenlecleucel (tisa-cel) for Relapsed/Refractory Follicular Lymphoma (ISPOR 2025) - P2 | "The estimated total weighted average AE cost (CRS, NEs, prolonged cytopenia, serious infections) was 51% lower with liso-cel versus axi-cel and 26% lower versus tisa-cel, mostly owing to lower rates of prolonged cytopenia and serious infections with liso-cel. This highlights the economic importance of differentiated safety profiles between CAR T cell therapies for treatment of R/R FL."

Adverse events • Clinical • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Oncology

Unmet Needs and Evidence Gaps Among Patients with DLBCL treated with CAR-T Therapy: A Systematic Literature Review (ISPOR 2025) - "Complete response rates were generally higher for axicabtagene ciloleucel (40-58%) than tisagenlecleucel (25-38%) or lisocabtagene maraleucel (15%). In this SLR, formal comparisons across CAR-T therapies and in different settings (i.e., inpatient vs. outpatient) in DLBCL are scarce. More research is needed to identify the most appropriate bridging therapy and treatments post-CAR-T failure to optimize outcomes for patients with different clinical profiles."

Clinical • Review • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Health-Related Quality of Life (HRQoL) of Large B-cell Lymphoma (LBCL) and Follicular Lymphoma (FL) Patients Treated with Axicabtagene Ciloleucel (Axi-cel) in Clinical Trials and the Real-World: A Targeted Literature Review (ISPOR 2025) - "Studies identified highlight the overall improved HRQoL of patients treated with axi-cel. Patients experienced substantial and generally quick recovery in functionality and symptoms across a breadth of HRQoL measures, emphasizing axi-cel's benefits beyond clinical efficacy."

Clinical • HEOR • Real-world • Real-world evidence • Review • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Analysis of Primary Causes of Delay in HTA/Reimbursement Decisions in the USA (2020-2024) (ISPOR 2025) - "Primary causes included incomplete or inconsistent submissions (e.g., Yescarta) and misalignment between sponsors and payers (e.g., Zolgensma)...Delays were driven by evidence complexity (e.g., Aduhelm), cost-effectiveness disagreements (e.g., Kymriah), and the requirement for real-world evidence (e.g., Luxturna)... Delays in HTA/reimbursement decisions in the USA during 2020-2024 were predominantly caused by incomplete submissions, disagreements over cost-effectiveness, and prolonged negotiations for high-cost therapies. Addressing these challenges, such as improving submission quality and aligning payer-sponsor expectations, could reduce delays and improve patient access."

Reimbursement • US reimbursement • Gene Therapies

The Evolving Role of Real-World Evidence in US Reimbursement Approvals: Trends and Case Studies (2020-2024) (ISPOR 2025) - "Example: Yescarta (Gilead Sciences) - Medicare reimbursement was supported by RWE demonstrating long-term efficacy in CAR-T therapy, contributing to $1 billion in annual revenue...Example: Ozempic (Novo Nordisk) - Cardiovascular outcome data underpinned reimbursement by private insurers, generating $4.4 billion revenue...Example: Aduhelm (Eisai/Biogen) - RWE enabled Medicare's conditional approval under a coverage-with-evidence-development framework, contributing to $1 billion revenue... The proportion of US reimbursement approvals influenced by RWE increased from 15% in 2020 to 55% in 2024, reflecting a paradigm shift in payer's value assessment. Implications: These findings highlight RWE's transformative potential in shaping reimbursement strategies, providing actionable insights to align on value-based healthcare objectives"

Case study • Clinical • HEOR • Real-world • Real-world evidence • Reimbursement • US reimbursement • Cardiovascular

Real-world Infusion and Post-Infusion Health Care Resource Use (HCRU) and Costs for CAR T Cell Treatment in Large B-Cell Lymphoma (LBCL): a Comparative Study of Liso-cel Versus Axi-cel (ISPOR 2025) - "Liso-cel infusion and 90-day follow-up costs were significantly lower than axi-cel. Results were robust to alternative cost inputs."

CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

A Systematic Review on Economic Evaluations of Comparisons Between CAR-T Therapies in Relapsed or Refractory Diffuse Large B-Cell Lymphoma (ISPOR 2025) - "Interventions assessed included axicabtagene ciloleucel (axi-cel; n=5), tisagenlecleucel (tisa-cel; n=4), and lisocabtagene maraleucel (liso-cel n=3). Taken together, our results suggest that axi-cel may be the most cost-effective CAR-T therapy for r/r DLBCL. More direct head-to-head comparisons of these therapies is required to inform both future economic evaluation studies and pricing adjustments of these therapies."

HEOR • Review • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Navigating Uncertainty Within a Re-evaluation Process: Epidemiological Approach vs Real-World Data in a Budget Impact Analysis for CAR T-cell Therapies in Quebec (ISPOR 2025) - "This case study examines the methodology used by INESSS for two CAR T-cell therapies (Kymriah and Yescarta) and the challenges faced when re-evaluating their budget impact analysis (BIA).Description: A reanalysis of the initial BIA, conducted in 2019 using an epidemiological approach, was performed. However, this approach is subject to uncertainty and partly based on assumptions derived from clinicians' input. A retrospective analysis using RWD provides more accurate estimates and should be favored in a re-evaluation context whenever possible."

CAR T-Cell Therapy • Clinical • HEOR • Real-world • Real-world evidence

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

The Improving Outcomes in Relapsed-Refractory Diffuse Large B Cell Lymphoma: The Role of CAR T-Cell Therapy. (PubMed, Curr Treat Options Oncol) - "In heavily pretreated patients, who have dismal outcomes with conventional therapy, all three approved products-tisangenlecleucel (tisa-cel), axicabtagene ciloleucel (axi-cel), and lisocabtagene maraleucel (liso-cel) have shown durable, unprecedented complete responses with the potential for cure. However, the barriers can be overcome, and CAR T therapy has the potential to become the standard of care in relapsed/refractory DLBCL. Furthermore, with advances in the scientific engineering of CAR products and the understanding of novel treatment modalities currently being tested in clinical trials, we believe that targeted cellular therapy will become the future of relapsed/refractory DLBCL treatment."

Journal • Review • B Cell Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Cytokine release syndrome and neurotoxicity following CD19 CAR-T in B-cell lymphoma. (PubMed, Transplant Cell Ther) - "High grades of CRS improved over time likely related to earlier intervention, development of ICANS is intrinsically related with CRS. These findings underscore the need for effective strategies to mitigate these toxicities and improve CAR-T safety."

Journal • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Long-term Dynamics and Integration Site Analysis of CAR-T Cell Therapy in Relapsed/Refractory Lymphoma and Multiple Myeloma: A Retrospective Study (ASGCT 2025) - "CAR-T products used included relma-cel (n=5), axi-cel (n=1), humanized CD19 CAR-T (n=2), BCMA single-target (n=5), BCMA/CS1 dual-target (n=4), and BCMA/CD38 dual-target (n=1). Among the 8 patients with relapsed/refractory lymphoma, all currently remain in complete remission. Of the 10 patients with multiple myeloma, 7 are in complete remission, while 3 have relapsed. Digital droplet PCR (ddPCR) monitoring showed that the levels of CAR-T cells in the body did not significantly differ based on the type of CAR-T product infused."

CAR T-Cell Therapy • Retrospective data • Hematological Disorders • Hematological Malignancies • Lymphoma • Multiple Myeloma • Oncology • CD38 • RPTOR • TET2

Does the Occurrence of ICANS After CAR-T Therapy Increase the Risk of Late Neurological Complications: A Real-World Data Analysis (ASGCT 2025) - "A total of 4,700 patients in this dataset received one of the US FDA-approved CAR-T therapies, including axicabtagene ciloleucel, tisagenlecleucel, lisocabtagene maraleucel, brexucabtagene autoleucel, and idecabtagene vicleucel. Future studies should consider potential confounding factors including age, prior cancer treatment, and underlying cancer type which could impact the risk of developing neurodegenerative disorders after CAR-T. Disease Focus of Abstract:Central Nervous System Disorders"

Clinical • Real-world • Real-world evidence • CNS Disorders • Movement Disorders • Oncology • Parkinson's Disease

Opposing roles of product CD27 and TIGIT expression in outcome to CAR-T cell therapy in R/R LBCL (AACR 2025) - "We leveraged ZUMA-1, -6 and -7 studies of R/R LBCL to discover product features associated with outcome to CAR-T cell therapy [Axicabtagene Ciloleucel (axi-cel)]. We explored ligand-receptor interactions between product cells and the tumor microenvironment, identifying CD27-CD70 and TIGIT-PVR axes as putative mediators of durable response and disease progression, respectively. Cytometry by time of flight (CyTOF) with 34 markers pertinent to T cell phenotyping and activation was performed on CAR-T cell products from ZUMA-1 (3rd line(L) LBCL; n = 57), ZUMA-6 (CAR-T cells + Atezolizumab; 3rd L LBCL; n = 14), and ZUMA-7 (2nd L LBCL; n = 45)... Using orthogonal methods on three clinical studies, we identified product features consistently associated with CAR T-cell efficacy in r/r LBCL, informing design of next-generation products and combinatorial approaches to improve outcome, including product enrichment of CD27+ CD8 T-SCM and TIGIT inhibition."

CAR T-Cell Therapy • IO biomarker • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CCR7 • CD27 • CD70 • CD8 • FAS • ITGB1 • NKG2D • TIGIT

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

Multi-omic characterization of tumor microenvironment evolution in LBCL across treatment lines: Insights from Atlas classification and axicabtagene ciloleucel trials (AACR 2025) - P1/2, P3 | "Recent molecular classifications of LBCL based on genetic factors shown to associate with response to R-CHOP and other chemo-immunotherapy based standard of care regimens have not been shown to associate with response to axi-cel in LBCL. We will present evolutionary changes though lines of therapy to less favorable tumor microenvironments and, through the projection of clinical trial samples, demonstrate that the Atlas is a powerful tool for exploring mechanisms behind treatment response and disease progression. This includes the association of immune cell populations, such as T-cell and macrophage phenotypes and overall immune cell contexture within the TME, and other biomarkers with disease progression and treatment response."

Biomarker • IO biomarker • Tumor microenvironment • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Two-stage CD8+ CAR T-cell differentiation in patients with large B-cell lymphoma (AACR 2025) - " To comprehensively investigate CAR T-cell differentiation in vivo, we performed single-cell, multi-modal, and longitudinal analyses of CD28-costimulated CAR T cells from infusion product and peripheral blood (day 8-28) of seven patients with r/r DLBCL who exhibited a complete response with axicabtagene ciloleucel. Our clonotypic and phenotypic analyses indicate that CD8+ CAR T cells undergo two distinct waves of clonal expansion in vivo... Our findings support a two-stage model for CD8+ CAR T-cell differentiation. Although two-stage differentiation is a novel phenomenon that has not yet been reported in the literature, the individual elements of our model are consistent with current understanding in the field. Importantly, our finding implies that manipulating the phenotypic composition of the infusion product may allow more precise control over in vivo CAR T-cell differentiation for modulating therapeutic efficacy."

CAR T-Cell Therapy • Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • B3GAT1 • CD8 • CX3CR1 • ENTPD1

Gilead Sciences Announces First Quarter 2025 Financial Results (Businesswire) - "Cell Therapy product sales decreased 3% to $464 million in the first quarter 2025 compared to the same period in 2024. Yescarta (axicabtagene ciloleucel) sales increased 2% to $386 million in the first quarter 2025 compared to the same period in 2024, primarily driven by higher average realized price and increased rest of world demand, partially offset by lower demand in the United States. Tecartus (brexucabtagene autoleucel) sales decreased 22% to $78 million in the first quarter 2025 compared to the same period in 2024, primarily reflecting lower demand in the United States."

Sales • Acute Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Mantle Cell Lymphoma

Hematologic toxicities with axicabtagene ciloleucel for B cell lymphomas in a majority minority population. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Matching-adjusted indirect comparison (MAIC) of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) and tisagenlecleucel (tisa-cel) for treatment of third-line or later (3L+) R/R follicular lymphoma (FL): Update with 24 months of liso-cel follow-up (FU). (ASCO 2025) - P2 | "Clinical Trial Registration Number: NCT04245839, NCT03105336, NCT03568461 The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology

Real world and Appalachian comparison of axicabtagene ciloleucel and lisocabtagene maraleucel in relapsed/refractory diffuse large B-cell lymphoma. (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 • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Sex-based differences in complications in patients with diffuse large B cell lymphoma receiving axicabtagene ciloleucel therapy. (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Clinical • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Prognostic value of circulating tumor DNA (ctDNA) detection by PhasED-Seq after axicabtagene ciloleucel (axi-cel) therapy in relapsed/refractory large B-cell lymphoma (LBCL). (ASCO 2025) - "The abstract will be released to the public on May 22, 2025 at 5:00 PM EDT"

Circulating tumor DNA • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology