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

Five-Year Follow-Up Analysis of ZUMA-5: Axicabtagene Ciloleucel in Relapsed/Refractory Indolent Non-Hodgkin Lymphoma. (PubMed, J Clin Oncol) - "Durable response and prolonged survival in FL were associated with robust early CAR T-cell expansion and naïve product phenotype. These findings confirm sustained responses and manageable safety with axi-cel in the long term among patients with R/R iNHL and its potential as a curative therapy in FL."

Journal • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Lymphoma • Marginal Zone Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

CAR T-cell therapy in secondary CNS lymphomas: A real-world study from the descar-t registry (ASH 2025) - P | "At the timeof CAR T-cell infusion, 109/195 (56%) patients were in complete (CR) or partial response (PR), and 84 (43%)had stable (SD) or progressive disease (PD) (missing data: 1%).One hundred thirty-eight (71%) patients received axi-cel, 26 (13%) tisa-cel, and 31 (16%) liso-cel. Efficacy and toxicity data, particularlywith respect to neurotoxicity, were consistent with those observed in systemic DLBCL. Further studies areneeded to support these results over the long term and to determine the optimal place of CAR T-cellswithin the therapeutic options of CNS lymphomas."

CAR T-Cell Therapy • Clinical • Real-world • Real-world evidence • B Cell Lymphoma • CNS Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma

A PILOT STUDY OF AXICABTAGENE CILOLEUCEL FOR THE TREATMENT OF RELAPSED/REFRACTORY PRIMARY AND SECONDARY CENTRAL NERVOUS SYSTEM LYMPHOMA (ICML 2025) - "Axi-cel has an acceptable safety profile in PCNSL and SCNSL with no apparent increased risk of ICANS or cerebral edema. Axi-cel is also effective for the treatment of CNSL (including in PCNSL) with a high CR rate that is more durable than available therapies. Extensive correlative studies offer unique insights into the CNS microenvironment and mechanisms of CAR T-cell therapy resistance and ICANS, identifying targets that will be explored to inform future CAR constructs/combinatorial strategies."

Clinical • B Cell Lymphoma • CNS Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Leukemia • Lymphoma • Myelodysplastic Syndrome • Oncology • Primary Central Nervous System Lymphoma • Secondary Central Nervous System Lymphoma • TCF7

Host immune biomarkers associated with infection risk after CAR T-cell therapy. (PubMed, J Infect) - "Longitudinal immune profiling identified distinct immunological signatures linked to infection risk and CAR-T-related toxicities. These findings suggest a role for immune monitoring in improving risk stratification and guiding supportive care after CAR-T therapy."

Biomarker • IO biomarker • Journal • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Infectious Disease • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL12A • RNASE1 • TNFA

HO161: HOVON 161: A phase II non-inferiority study comparing point-of-care produced CAR T-cell to commercial CAR T-cells in patients with relapsed/refractory Non-Hodgkin Lymphoma (clinicaltrialsregister.eu) - P1/2 | N=340 | Active, not recruiting | Sponsor: Universitair Medisch Centrum Groningen | Recruiting ➔ Active, not recruiting

Enrollment closed • Head-to-Head • B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • BCL2 • BCL6

Second-line axicabtagene ciloleucel in large B-cell lymphoma ineligible for transplantation: ALYCANTE final analysis. (PubMed, Hemasphere) - No abstract available

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

Acalabrutinib in Combination with Anti-CD19 Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory B-Cell Lymphoma: A Phase I/II Study of Safety, Efficacy and Immune Correlative Analysis (ASH 2023) - P1/2 | "BTK inhibitors, ibrutinib and acalabrutinib are immunomodulatory and may enhance CAR-T expansion, engraftment and tumor clearance while decreasing the frequency and severity of CRS in chronic lymphocytic leukemia (Qin, et al...Three (20%) patients had grade 3 ICANS which resolved with dexamethasone and anakinra or tocilizumab...Conclusions Acalabrutinib successfully bridged most patients in this trial when given concurrently with axi-cel and safely maintained high CR rates. CRP and ferritin levels were typically only modestly elevated after cell infusion. Severe CRS was not observed and high-grade ICANS was uncommon."

CAR T-Cell Therapy • Clinical • Combination therapy • IO biomarker • P1/2 data • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • IL6 • MYC

NKTR-255 Enhances Complete Response Following CD19 CAR-T in Patients with Relapsed/Refractory Large B-cell Lymphoma. (PubMed, Blood Adv) - P2/3 | "In this phase 2, randomized, double-blind, placebo-controlled, multicenter study of NKTR-255 versus placebo following CD19 CAR T-cell therapy, eligible patients with R/R LBCL were treated with one of two FDA-approved CAR T-cell products, axicabtagene ciloleucel (axi-cel) or lisocabtagene maraleucel (liso-cel). NKTR-255 was well-tolerated, safe, and augmented CR6 for LBCL patients. Based on the findings, additional confirmatory studies with NKTR-255 as adjuvant treatment to CAR T-cell, including other cellular therapies, are warranted (ClinicalTrials.gov number NCT05664217)."

Clinical • Journal • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD8

Outcome of large B-cell lymphoma patients treated with tafasitamab plus lenalidomide either before or after CAR-T-cells. (PubMed, Blood Adv) - "We analyzed large B-cell lymphoma patients in the DESCAR-T registry treated with axi-cel or tisa-cel in ≥3rd line (L3+) and TAFA-LEN before (n=15, 'TL-pre-CAR-T' set) or directly after (n=52, 'TL-post-CAR-T' set) CAR T-cell. The bORR, bCRR, 6-month PFS and OS rates after CAR T-cell infusion were 45.5%, 36.4%, 20.1% and 58.2%, respectively. Neither TAFA-LEN nor comparative salvage treatments improved outcomes of patients who relapsed after CAR T-cell."

CAR T-Cell Therapy • Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Reusable Pipeline for Converting Real-World Lymphoma Registry Data to CDISC Standards: Implementation and Validation Using Lymphoma Epidemiology of Outcomes Consortium for Real World Evidence. (PubMed, JCO Clin Cancer Inform) - "This work demonstrates a practical, reusable pipeline for CDISC-standardized RWD in lymphoma."

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

A Real-World Study of the Effectiveness and Safety of Post-Tafasitamab Chimeric Antigen Receptor T-Cell Therapy in Relapsed/Refractory Diffuse Large B-Cell Lymphoma (SOHO 2026) - " This retrospective, US and EU physician-abstracted medical chart review study collected data for adults with R/R DLBCL who received tafasitamab (±lenalidomide) and subsequent CAR-T in second-line (2L), 3L, or 4L...CAR-T therapies administered were axicabtagene ciloleucel (65.1%), followed by lisocabtagene maraleucel (21.9%) and tisagenlecleucel (13.0%)... This large, real-world study indicates that prior exposure to tafasitamab does not appear to compromise the effectiveness or safety of subsequent CAR-T therapy in patients with R/R DLBCL. These real-world study findings support the sequencing strategy of tafasitamab followed by CAR-T. Funding: This study was funded by Incyte Corporation."

CAR T-Cell Therapy • Clinical • IO biomarker • Real-world • Real-world evidence • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19

A Phase 2 Study of Nivolumab for Relapsed/Refractory Multiple Myeloma or Non-Hodgkin Lymphoma Following CAR-T Therapy (ASH 2023) - P2 | "In a recent multicenter NHL cohort (Major Blood Advances 2023), responses were similarly low with both pembrolizumab and nivolumab (nivo)...In NHL, the responding patient – who had had a DS4 response at Day +30 then a DS5 response at Day +60 following axi-cel before starting nivo one month later – achieved a complete response (DS3) including resolution of hepatic and splenic lymphomatous lesions...Two irAEs (one Gr2 pneumonitis, one Gr2 rash) occurred, both in non-responders, and both resolved with brief courses of prednisone... We found that responses to PD-1 blockade following CAR-T failure are uncommon, confirming prior studies in NHL which demonstrate poor activity in this setting. Our 18% ORR with post-CAR-T nivo in R/R MM (2/11 pts) is notably higher than the 4% ORR (1/27 pts) reported with nivo monotherapy in R/R MM (Lesokhin JCO 2016), although conclusions are difficult to draw with small n. Day +28 responses following a single dose of nivo 480mg were..."

IO biomarker • P2 data • Anemia • Cardiovascular • Hematological Disorders • Hematological Malignancies • Infectious Disease • Lymphoma • Multiple Myeloma • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Plasmacytoma • Pneumonia • Septic Shock • PD-L1

A phase 1b trial of the EZH2 inhibitor tazemetostat combined with CAR T cell therapy in B cell lymphomas (ASH 2025) - "4 patients had TP53 mutation or deletion(31%), and of the 7 DLBCL patients, 4 had high-grade myc translocation (57%) and 3 were transformedfrom indolent lymphomas (43%).Following tazemetostat pre-treatment and bridging, 5 patients received axi-cel (38%), 5 liso-cel (38%), 2tisa-cel (15%), and 1 brexu-cel (8%). Addition of the EZH2 inhibitor tazemetostat to the CAR T pre-collection, bridging, and post-infusion periods is feasible, and without early evidence of adverse impact on safety. Initial efficacy data isencouraging but requires additional patients and follow up. Preliminary correlative findings suggest apositive impact of tazemetostat oral administration on the endogenous immune system, tumormicroenvironment, and T cell product in patients."

CAR T-Cell Therapy • IO biomarker • P1 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hemophagocytic lymphohistiocytosis • Indolent Lymphoma • Infectious Disease • Lymphoma • Mantle Cell Lymphoma • Neutropenia • Non-Hodgkin’s Lymphoma • Thrombocytopenia • CD4 • CD8 • MYC • TP53

Itacitinib Pre-modulation in DLBCL Receiving CAR T Cell Therapy (clinicaltrials.gov) - P2 | N=27 | Recruiting | Sponsor: H. Lee Moffitt Cancer Center and Research Institute | Trial primary completion date: Jun 2026 ➔ Feb 2027

Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CRP • JAK1

Comparative Efficacy and Safety of Approved Therapies in ≥3L Relapsed/Refractory Large B-Cell Lymphoma: A Bayesian Network Meta-Analysis (SOHO 2026) - "Background: Multiple novel agents are approved for ≥3L relapsed/refractory large B-cell lymphoma, including chimeric antigen receptor T-cell (CAR-T) products (axicabtagene ciloleucel [axi-cel], lisocabtagene maraleucel [liso-cel], tisagenlecleucel [tisacel]), bispecific antibodies (epcoritamab, glofitamab, mosunetuzumab), antibody-drug conjugates (polatuzumab vedotin + bendamustine, rituximab [pola-BR], loncastuximab tesirine), and others (tafasitamab + lenalidomide, selinexor). CAR-T therapies ranked highest for CR rate but with greater toxicity and selection bias. Among bispecific antibodies, epcoritamab ranked among the most favorable for combined efficacy and safety (SUCRA, 58.3% vs 56.1% for glofitamab and 47.8% for mosunetuzumab). Given the near-disconnected, star-topology network and predominantly single-arm data, results carry very low certainty per CINeMA and should be interpreted cautiously."

Retrospective data • B Cell Lymphoma • Hematological Malignancies • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Real-World Comparison of Axi-Cel and Liso-Cel in Richter Transformation (SOHO 2026) - "We compared the efficacy and safety of axicabtagene ciloleucel (axi-cel) and lisocabtagene maraleucel (lisocel) in patients with RT...Propensity score matching (1:1) was performed for age, sex, race, prior chemotherapy exposure, and prior treatment with BTK inhibitors and venetoclax... In this real-world RT cohort, axi-cel and liso-cel demonstrated comparable survival outcomes, hospice utilization, and toxicity profiles. These findings provide comparative evidence supporting the clinical utility of both products in this high-risk disease setting. CAR-T: chimeric antigen receptor T-cell, CD: cluster of differentiation, CI: confidence interval, CLL: chronic lymphocytic leukemia, CRS: cytokine release syndrome, DLBCL: diffuse large B-cell lymphoma, HR: hazard ratio, ICD-10: International Classification of Diseases, Tenth Revision, RT: Richter transformation."

Clinical • Real-world • Real-world evidence • B Cell Lymphoma • Chronic Lymphocytic Leukemia • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Richter's Syndrome • Small Lymphocytic Lymphoma

Itacitinib for the Prevention of Immune Effector Cell Therapy–Associated Cytokine Release Syndrome: Results from the Phase 2 Incb 39110-211 Placebo-Controlled Randomized Cohort (ASH 2023) - P2 | "Protocol did not allow tocilizumab for treatment of grade 1 CRS unless CRS did not improve after 72 hours of supportive treatment. Results from the randomized, placebo-controlled portion of Study INCB 39110-211 have shown prophylaxis treatment with itacitinib 200 mg bid to be well tolerated and resulted in a lower rate and grade of CRS and ICANS after lymphoma treatment with axicabtagene ciloleucel. Incidence of grade 3/4 neutropenia and thrombocytopenia not resolved at Day 28 was higher with itacitinib vs placebo. Rates of severe infections were comparable in both arms."

Clinical • Cytokine release syndrome • IO biomarker • P2 data • B Cell Lymphoma • Follicular Lymphoma • Hematological Disorders • Hematological Malignancies • Hypotension • Infectious Disease • Inflammation • Large B Cell Lymphoma • Lymphoma • Nephrology • Neutropenia • Non-Hodgkin’s Lymphoma • Oncology • Septic Shock • Thrombocytopenia

Antigen Escape in Relapsed/Refractory Large B-Cell Lymphoma: A Case Series of CD20 Expression Loss After CD20-Directed Therapy (SOHO 2026) - "Context: CD20-directed therapy remains foundational in the management of LBCL, yet relapsed disease may emerge with loss of CD20 expression, limiting the utility of rituximab- or obinutuzumab-based regimens or bispecific antibodies...All patients had received prior CD20-directed therapy, most commonly rituximab-containing regimens, including R-CHOP, REPOCH, R-GemOx, R-ICE, rituximab-lenalidomide, or bendamustine-rituximab. Several also received contemporary salvage approaches, including polatuzumab-based therapy, epcoritamab, tafasitamab-lenalidomide, radiation, lymphodepleting chemotherapy, and CAR-T therapy with axicabtagene ciloleucel or tisagenlecleucel... CD20-negative conversion is a clinically consequential pattern of relapse in heavily pretreated LBCL. This series highlights the importance of repeat biopsy at progression to reassess targetable antigen expression and avoid ineffective recycling of CD20-directed therapy. Antigen reassessment should inform..."

Clinical • IO biomarker • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • CD19 • CD20 • CD22

Phase II Trial of Axicabagene Ciloleucel and Glofitamab As Second-Line Therapy for Patients with Relapsed or Refractory Large B-Cell Lymphoma (ASH 2024) - P2 | "Standard lymphodepleting chemotherapy with fludarabine 30mg/m2 and cyclophosphamide 500mg/m2 will be given, followed by Axi-cel infusion. Glofitamab step-up dosing will be repeated in cycle 3 without re-treatment with obinutuzumab...The sample size of 40 patients will allow for 80% power at the significance level of 0.05 to determine if the historical response rate of 0.65 is different from the projected experimental response rate of 0.825. Exploratory analyses are planned to evaluate the tumor profile and antigen density, single cell multiome sequencing and whole exome sequencing, ctDNA kinetics, and immune cell fitness."

Clinical • P2 data • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Immunology • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology

Devimistat Results in a Low Complete Remission Rate in Heavily Pre-Treated Burkitt Lymphoma (ASH 2024) - P2 | "The first CR patient was 40 years old, HIV positive with a viral load of 23 copies/mL, and 4 previous lines of therapy (CODOX-M/R-IVAC, R-ICE, pembrolizumab+acalabrutinib, R-methotrexate cytarabine) before receiving 11 cycles of devimistat...The second CR patient was 21 years old, HIV negative, received 6 previous lines of therapy (R-CHOP, DA-R-EPOCH, R-HCVAD/R-MA and IT MTX, R-Hyper cyclophosphamide, axi-cel, allogeneic SCT)...(Manji, ASH,2021) Despite few treatment options, it was difficult to enroll pts who were often ineligible due to poor performance status, CNS disease or logistical constraints, leading to study closure. Considering the dismal prognosis with the current standard of care, efforts should be made to improve the outcome of those with high-risk BL with their first line of therapy."

Clinical • Burkitt Lymphoma • CNS Disorders • Hematological Disorders • Hematological Malignancies • Hepatology • High-grade B-cell lymphoma • Human Immunodeficiency Virus • Infectious Disease • Lymphoma • Neutropenia • Oncology • Thrombocytopenia • CD4

Itacitinib for the Prevention of IEC Therapy-Associated CRS: Results From the Two-Part Phase 2 INCB 39110-211 Study. (PubMed, Blood) - P2 | "Patients in part 1 received once-daily itacitinib 200 mg 3 days before IEC therapy (axicabtagene ciloleucel [axi-cel], brexucabtagene autoleucel, or tisagenlecleucel) through Day 26, with guidelines for use of other CRS/ICANS interventions. Importantly, itacitinib did not impact IEC therapy efficacy (objective response rate at 6 months: 39.1% for itacitinib 200 mg bid vs 26.1% for placebo). Trial registration: clinicaltrials.gov; #NCT04071366."

Journal • P2 data • Hematological Disorders • Hematological Malignancies • Oncology

A patient's experience with follicular lymphoma from diagnosis to cure: the life-changing impact of CAR T-cell therapy. (PubMed, Future Oncol) - P2 | "In 2018, with extensive tumor burden and nearing kidney failure, Laurie enrolled in the ZUMA-5 clinical trial (NCT03105336) and received her seventh and final treatment, a chimeric antigen receptor (CAR) T-cell therapy called axicabtagene ciloleucel (axi-cel)...However, all her side effects from CAR T-cell therapy resolved, and her quality of life returned to her pre-infusion state within 3-4 months. By sharing her experience, Laurie aims to raise awareness for this life-saving and likely curative treatment across multiple audiences that may be impacted by FL, including patients, clinicians, families/caregivers, and advocates."

Journal • Follicular Lymphoma • Hematological Malignancies • Lymphoma • Oncology • Renal Disease

Long-Term Follow-Up Study After Gene-Modified Cell Treatment in Kite Studies (clinicaltrials.gov) - P=N/A | N=1500 | Enrolling by invitation | Sponsor: Kite, A Gilead Company | N=1000 ➔ 1500

Enrollment change • Hematological Malignancies • Immunology • Oncology

A Proof-of-Principle of Split-Course Bridging Radiotherapy (SC-BRT) Prior to CAR T-Cell Therapies for Relapsed or Refractory B-Cell Lymphomas: A Phase 1a Pilot Cohort (ASH 2024) - P1 | "The feasibility outcome was achieved, as all pts successfully received SC-BRT and standard cyclophosphamide/fludarabine LD followed by commercial lisocabtagene maraleucel (n=4) or axicabtagene ciloleucel (n=2)...One patient was treated with steroids and tocilizumab for mild CRS and the patient with grade 5 CRS received steroids, tocilizumab and siltuximab but expired on day +6...This is the first reported delivery of any form of RT following administration of LD chemotherapy potentially opening the door for novel CART conditioning approaches. Given successful completion of Phase 1a, 14 additional patients are now being recruited to the Phase 1b expansion cohort (9 already accrued, data not presented) to confirm safety, assess preliminary outcomes and explore possible immune augmentation."

CAR T-Cell Therapy • P1 data • B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • PTPRC

Tocilizumab Prophylaxis Following Axicabtagene Ciloleucel in Relapsed or Refractory Large B-cell Lymphoma. (PubMed, Transplant Cell Ther) - "Based on these findings, prophylactic tocilizumab is not recommended to prevent CAR T-cell-related adverse events, and beneficial effects of prophylactic levetiracetam remain uncertain in patients with R/R LBCL."

Journal • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • IL6R