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ZUMA-24: A PHASE 2, OPEN-LABEL STUDY OF AXICABTAGENE CILOLEUCEL IN PATIENTS WITH RELAPSED/REFRACTORY LARGE B-CELL LYMPHOMA GIVEN OUTPATIENT WITH CORTICOSTEROIDS B Introduction: b Axicabtagene ciloleucel (Axi-cel) is an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy approved for the treatment of adults with relapsed or refractory ( I R i / I R i ) large B-cell lymphoma (LBCL) after >=2 lines of systemic therapy and for I R i / I R i LBCL within 12 months of first-line chemoimmunotherapy. Key exclusion criteria include >1 prior line of therapy for LBCL, prior stem cell transplant, and prior anti-CD19 or CAR T-cell therapy. [Extracted from the article]

We performed a Phase I and pharmacokinetic study of once-daily, intravenously administered busulfan in the setting of a reduced-intensity preparative regimen and matched sibling donor allogeneic stem cell transplantation for treatment of metastatic renal cell carcinoma. Seven male patients with metastatic renal cell carcinoma received intravenously administered busulfan at 3.2 mg/kg once daily on day -10 and day -9, fludarabine at 30 mg/m2 on day -7 through day -2, and equine antithymocyte globulin at 15 mg/kg per day on day -5 through day -2. The mean area under the plasma concentration-time curve (AUC) and the half-life of the first dose of intravenously administered busulfan were 6,253 microM x minute (range, 5,036-7,482 microM x minute) and 3.37 hours (range, 2.54-4.00 hours), respectively. The AUC was higher than predicted from extrapolation of AUC data for the same total dose of intravenously administered busulfan divided into four doses daily. Patients experienced greater than expected regimen-related toxicity for a reduced-intensity preparative regimen, and the study was stopped. In conclusion, this preparative regimen was associated with unacceptable regimen-related toxicity among patients with metastatic renal cell carcinoma. [ABSTRACT FROM AUTHOR]

Abstract: We analyzed access barriers to anti-CD19+ chimeric antigen receptor T cells (CARTs) for non-Hodgkin lymphoma (NHL) within a community-based transplant and cell therapy network registry. A total of 357 intended recipients for approved anti-CD19+ CARTs were identified between 2018 to 2022. The median age at referral was 61 years; referral years were 2018 (4%), 2019 (14%), 2020 (18%), 2021 (26%), and 2022 (38%). Diagnoses included diffuse large B cell (69%), follicular (13%), follicular/large (7%), mantle cell (4%), or other (7%). Axicabtagene ciloleucel (62%), tisagenlecleucel (16%), brexucabtagene autoleucel (13%), and lisocabtagene maraleucel (9 %) were infused into 182 patients. The median durations between referral to consultation, consultation to apheresis, and collection to infusion were 11, 107, and 32 days, respectively. The median duration from consultation to CART infusion declined steadily from 207 days in 2019 to 108 days in 2022 (P < .0001). A total of 124 patients (41%) did not receive CART, mostly for disease progression (34%) or poor health (15%). Multivariable logistic regression showed no significant differences in demographic, financial, or social determinants compared with those receiving CART. Notably, the proportion of ineligible patients declined from 53% in 2018-2020 to 34% by 2021-2022 (P = .001). In conclusion, 41% of community patients were unable to access timely CART therapy, mostly due to attrition from disease-related causes, and the overall time to infusion exceeded 4 months. Time to infusion and the proportion receiving CARTs improved over time. Reducing time to apheresis, early referral, and attention to salvage/bridging strategies are necessary., (© 2025 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: FT596 is an induced pluripotent stem-cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cell therapy with three antitumour modalities: a CD19 CAR; a high-affinity, non-cleavable CD16 Fc receptor; and interleukin-15-interleukin-15 receptor fusion. In this study, we aimed to determine the recommended phase 2 dose (RP2D) and evaluate the safety and tolerability of FT596 as monotherapy and in combination with rituximab. We also aimed to evaluate the antitumour activity and characterise the pharmacokinetics of FT596 as monotherapy and in combination with rituximab., Methods: In this phase 1, first-in-human trial, we evaluated FT596 in patients with relapsed or refractory B-cell lymphoma at nine sites in the USA. Patients who had received at least one previous systemic therapy and had no curative treatment options were eligible for inclusion. FT596 was administered after conditioning chemotherapy without rituximab (regimen A) or combined with rituximab (regimen B). The study consisted of a dose-escalation phase using a 3 + 3 design, with dose escalation commencing at 3 × 10 7 viable cells as a single dose on day 1 and done independently for individual regimens. A treatment cycle consisted of conditioning chemotherapy with cyclophosphamide (500 mg/m 2 ) and fludarabine (30 mg/m 2 ) intravenously on days -5 to -3, followed by FT596 administered at various doses and schedules, without (regimen A) or with (regimen B) a single dose of rituximab (375 mg/m 2 ) intravenously on day -4. Supportive care was determined by the treating investigator. Patients were observed for dose-limiting adverse events for 28 days. Patients who tolerated therapy and derived clinical benefit could receive subsequent cycles of study treatment, with modification of conditioning chemotherapy dose if clinically indicated. The dose-expansion phase evaluated additional patients at selected doses and dosing schedules that had been found to be tolerable. The primary endpoints of the study were the incidence and nature of dose-limiting toxicities within each dose-escalation cohort to determine the maximum tolerated dose or maximum assessed dose to establish the RP2D and the incidence, nature, and severity of adverse events, with severity determined according to National Cancer Institute Common Toxicity Criteria and Adverse Events version 5·0. The trial was registered with ClinicalTrials.gov, NCT04245722., Findings: Between March 19, 2020, and Jan 12, 2023, 86 patients with B-cell lymphoma received FT596 on regimen A (n=18) or regimen B (n=68). 22 (26%) of 86 patients were female and 72 (84%) of 86 patients were White. Patients had received a median of four previous lines of therapy (range 1-11) and 33 (38%) of 86 patients had received previous CAR T-cell therapy. The maximum tolerated dose was not reached. Cytokine release syndrome was reported in one (6%) of 18 patients (maximum grade 1) on regimen A and nine (13%) of 68 patients on regimen B (six with maximum grade 1 and three with grade 2). Neurotoxicity was not observed., Interpretation: FT596 was well tolerated as monotherapy or with rituximab and induced deep and durable responses in patients with indolent and aggressive lymphomas and the RP2D was preliminarily identified to be 1·8 × 10 9 cells for three doses per cycle. This study supports that cell therapy using iPSC-derived, gene-modified NK cells is a potent platform for cancer treatment and suggests that such a platform might address limitations of currently available immune cell therapies, including manufacturing time, heterogeneity, access, and cost., Funding: Fate Therapeutics., Competing Interests: Declaration of interests AG received consulting fees from Amgen, Atara, Bristol Myers Squibb, CRISPR Therapeutics, Kite, and Wugen, and received research funding from Amgen, Genentech, Securabio, and Kite. VB received research funding from Incyte, Citius, and Gamida Cell. KP received consulting fees from Adaptive, ADC Therapeutics, AstraZeneca, BeiGene, Bristol Myers Squibb, Caribou Therapeutics, Fate Therapeutics, Genentech-Roche, Janssen-Pharmacyclics, Kite, Lilly-Loxo, Merck, Morphosys, Sana, and Xencor, and received honoraria from AstraZeneca and Kite. JHP received consulting fees from Pfizer, Takeda, Galapagos, In8Bio, Adaptive Biotechnologies, Caribou Biosciences, Synthekine, Amgen, Novartis, Bristol Myers Squibb, Kite Pharma, Kura Oncology, Servier, Autolus, Curocell, Minerva, Sobi, Be Bio, Beigene, and GC Cell, participated in advisory boards for Affyimmune, Bright Pharmaceuticals, Allogene, and Artiva Biotherapeutics, and holds stock in Curocell. IF received consulting fees from AbbVie, BeiGene, Genentech, Genmab, Kite, and Vencerx, and served on an advisory committee at Vincerx. CB served as an unpaid board member for the Foundation of Accreditation of Cellular Therapy. PAR received consulting fees from AbbVie, Bristol Myers Squibb, Janssen, Novartis, BeiGene, Kite-Gilead, Intellia Therapeutics, Sana Biotechnology, CVS Caremark, Genmab, Pharmacyclics, Genentech-Roche, ADC Therapeutics, Nektar Therapeutics, and Nurix Therapeutics, and received travel support from Nektar Therapeutics and Adaptive Biotechnologies. CSD received consulting fees from Merck and Bristol Myers Squibb, and participated in advisory boards for Merck, Bristol Myers Squibb, and Cargo Therapeutics. CW, CB, LW, DP, JG, MD, BV, and RLE are employees of and hold stock in Fate Therapeutics. PS is a consultant for Roche-Genentech, AbbVie-Genmab, Ipsen, Kite-Gilead, Hutchison MediPharma, AstraZeneca-Acerta, ADC Therapeutics, Sobi, and TG Therapeutics; he has received research funds from Sobi, AstraZeneca-Acerta, ALX Oncology, and ADC Therapeutics., (Copyright © 2025 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Abstract: Lisocabtagene maraleucel (liso-cel) is an autologous, CD19-directed, 4-1BB chimeric antigen receptor (CAR) T-cell product approved for relapsed/refractory (R/R) large B-cell lymphoma (LBCL). We present the OUTREACH primary analysis, evaluating the safety and efficacy of outpatient monitoring after liso-cel treatment at community sites in the United States. Adults with R/R LBCL after ≥2 prior lines of therapy received liso-cel. Outpatient vs inpatient monitoring was per investigator discretion. The primary end points were incidences of grade ≥3 cytokine release syndrome (CRS), neurological events (NEs), prolonged cytopenia, and infections. Efficacy was a secondary end point. Eighty-two patients received liso-cel (outpatient monitored, 70%; inpatient monitored, 30%). The median follow-up was 10.6 months (range, 1.0-24.5). In outpatients and inpatients, grade ≥3 CRS occurred in 0% and 0%, NEs in 12% and 4%, infections in 12% and 8%, and prolonged cytopenia in 33% and 32%, respectively. Among outpatients, 25% were never hospitalized after infusion, and 32% were hospitalized ≤72 hours after the day of infusion; the median time to hospitalization was 5.0 days (range, 2-310). The median initial hospitalization duration after liso-cel was 6.0 days (range, 1-28) for outpatients and 15.0 days (range, 3-31) for inpatients. Objective response rate was 80%, complete response rate was 54%, and the median duration of response was 14.75 months (95% confidence interval, 5.0 to not reached). OUTREACH is, to our knowledge, the first and largest study to prospectively assess CAR T-cell therapy with outpatient monitoring in community-based medical centers. Liso-cel demonstrated meaningful efficacy with favorable safety in patients with R/R LBCL. Data support the feasibility of liso-cel administration at community sites with outpatient monitoring. This trial was registered at www.ClinicalTrials.gov as #NCT03744676., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Abstract: Immune effector cells (IECs) include a broad range of immune cells capable of modulating several disease states, including malignant and nonmalignant conditions. The growth in the use of IECs as both investigational and commercially available products requires medical institutions to develop workflows/processes to safely implement and deliver transformative therapy. Adding to the complexity of this therapy are the variety of targets, diseases, sources, and unique toxicities that a patient experiences following IEC therapy. For over 25 years, the Foundation for the Accreditation of Cellular Therapy (FACT) has established a standard for the use of cellular therapy, initially with hematopoietic cell transplantation (HCT), and more recently, with the development of standards to encompass IEC products such as chimeric antigen receptor (CAR)-T cells. To date, IEC therapy has challenged the bandwidth and infrastructure of the institutions offering this therapy. To address these challenges, FACT has established a programmatic framework to improve the delivery of IEC therapy. In this study, we outline the current state of IEC program development, accreditation, and solutions to the challenges that programs face as they expand their application to novel IEC therapy., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Relapse after CD19-directed chimeric antigen receptor T-cell (CAR-T) therapy for large B-cell lymphoma (LBCL) is commonly ascribed to antigen loss or CAR-T exhaustion. Multiantigen targeting and programmed cell death protein-1 blockade are rational approaches to prevent relapse. Here, we test CD19/22 dual-targeting CAR-T (AUTO3) plus pembrolizumab in relapsed/refractory LBCL (NCT03289455). End points include toxicity (primary) and response rates (secondary). Fifty-two patients received AUTO3 and 48/52 received pembrolizumab. Median age was 59 years (range, 27-83), 46/52 had stage III/ IV disease and median follow-up was 21.6 months. AUTO3 was safe; grade 1-2 and grade 3 cytokine release syndrome affected 18/52 (34.6%) and 1/52 (1.9%) patients, neurotoxicity arose in 4 patients (2/4, grade 3-4), and hemophagocytic lymphohistiocytosis affected 2 patients. Outpatient administration was tested in 20 patients, saving a median of 14 hospital days per patient. Overall response rates were 66% (48.9%, complete response [CR]; 17%, partial response). Median duration of remission (DOR) for CR patients was not reached and for all responding patients was 8.3 months (95% confidence interval [CI]: 3.0-not evaluable). 54.4% (CI: 32.8-71.7) of CR patients and 42.6% of all responding patients were projected to remain progression-free at ≥12 months. AUTO3 ± pembrolizumab for relapsed/refractory LBCL was safe and delivered durable remissions in 54.4% of complete responders, associated with robust CAR-T expansion. Neither dual-targeting CAR-T nor pembrolizumab prevented relapse in a significant proportion of patients, and future developments include next-generation-AUTO3, engineered for superior expansion in vivo, and selection of CAR binders active at low antigen densities., (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Introduction: Cytokine release syndrome is a life-threatening hyper-inflammatory state induced by immune effector cell therapy. Anti-interleukin 6-(IL-6) therapy, such as tocilizumab, is the standard treatment for cytokine release syndrome since it reverses symptoms without compromising immune effector cell therapy efficacy. Glucocorticoids are reserved for refractory or severe cytokine release syndrome due to concern for attenuating antitumor activity. Optimizing the timing of tocilizumab could avoid glucocorticoid use and improve outcomes. This study assesses tocilizumab timing on patient outcomes and healthcare resource utilization., Methods: This is a retrospective single-institution analysis of 28 patients who received tocilizumab for cytokine release syndrome secondary to immune effector cell therapy. Patients were categorized into two groups: Early Tocilizumab (within 24 h) or Late Tocilizumab groups (more than 24 h) from fever onset. The composite primary endpoint was glucocorticoid use, intensive care unit admission, or inpatient mortality. Secondary outcomes include comparing the various presentations of cytokine release syndrome, need for vasopressors, length of stay, rates of neurotoxicity, and C-reactive protein and ferritin trends., Results: The Early Tocilizumab group presented with more rapid fever onset (35 vs.113 h, P  = 0.017) and higher maximum cytokine release syndrome grade (Median, Grade 2 vs. Grade 1, P  = 0.025). Additionally, the Early Tocilizumab group required more doses of tocilizumab (Median, 2 vs. 1, P  = 0.037). Despite the difference in cytokine release syndrome presentation, the primary composite endpoint was not statistically different between groups., Conclusion: Earlier onset of fever appears to be associated with more severe, progressive cytokine release syndrome requiring multiple doses of anti-interleukin-6 therapy. Prompt and aggressive tocilizumab treatment could be protective against the negative consequences of cytokine release syndrome.

Adoptive cellular therapies have revolutionized the management of hematologic malignancies, particularly lymphoma and multiple myeloma. These therapies targeting disease-specific antigens, such as CD19 in lymphoma and B cell maturation antigen in multiple myeloma, are efficacious and well-tolerated compared with conventional chemotherapies. Unfortunately, their potential remains unrealized in acute myeloid leukemia (AML). This is because most targetable antigens on AML cells are also expressed on healthy myeloid hematopoietic stem cells (HSC). Therefore, targeting them results in severe myeloablative effects and pancytopenia. Several strategies have been devised to overcome this barrier, including identifying AML-specific antigens, limiting CAR-T cell persistence to prevent prolonged myeloablation, and creating AML-specific antigens through manipulating HSCs prior to allogenic transplant. In this review, we discuss these strategies and the ongoing clinical trials on adoptive cellular therapies in AML, limiting our focus to chimeric antigen receptor-T cells (CAR-T) and chimeric antigen receptor-natural killer cells (CAR-NK).

Background: ADP-A2M10 specific peptide enhanced affinity receptor (SPEAR) T cells (ADP-A2M10) are genetically engineered autologous T cells that express a high-affinity melanoma-associated antigen A10 (MAGE-A10)-specific T-cell receptor (TCR) targeting MAGE-A10 + tumors in the context of human leukocyte antigen (HLA)-A*02. ADP-0022-003 was a phase I dose-escalation trial that aimed to evaluate the safety and antitumor activity of ADP-A2M10 in non-small cell lung cancer (NSCLC) (NCT02592577)., Methods: Eligible patients were HLA-A*02 positive with advanced NSCLC expressing MAGE-A10. Patients underwent apheresis; T cells were isolated, transduced with a lentiviral vector containing the TCR targeting MAGE-A10, and expanded. Patients underwent lymphodepletion with varying doses/schedules of fludarabine and cyclophosphamide prior to receiving ADP-A2M10. ADP-A2M10 were administered at 0.08-0.12×10 9 (dose group 1), 0.5-1.2×10 9 (dose group 2), and 1.2-15×10 9 (dose group 3/expansion) transduced cells., Results: Eleven patients (male, n=6; female, n=5) with NSCLC (adenocarcinoma, n=8; squamous cell carcinoma, n=3) were treated. Five, three, and three patients received cells in dose group 1, dose group 2, and dose group 3/expansion, respectively. The most frequently reported grade ≥3 adverse events were lymphopenia (n=11), leukopenia (n=10), neutropenia (n=8), anemia (n=6), thrombocytopenia (n=5), and hyponatremia (n=5). Three patients presented with cytokine release syndrome (grades 1, 2, and 4, respectively). One patient received the highest dose of lymphodepletion (fludarabine 30 mg/m 2 on days -5 to -2 and cyclophosphamide 1800 mg/m 2 on days -5 to -4) prior to a second infusion of ADP-A2M10 and had a partial response, subsequently complicated by aplastic anemia and death. Responses included: partial response (after second infusion; one patient), stable disease (four patients), clinical or radiographic progressive disease (five patients), and not evaluable (one patient). ADP-A2M10 were detectable in peripheral blood and in tumor tissue. Peak persistence was higher in patients who received higher doses of ADP-A2M10., Conclusions: ADP-A2M10 demonstrated an acceptable safety profile and no evidence of toxicity related to off-target binding or alloreactivity. There was persistence of ADP-A2M10 in peripheral blood as well as ADP-A2M10 trafficking into the tumor. Given the discovery that MAGE-A10 and MAGE-A4 expression frequently overlap, this clinical program closed as trials with SPEAR T cells targeting MAGE-A4 are ongoing., Competing Interests: Competing interests: AG holds stock options in Adaptimmune. AJO has received research contracts from Alkermes, Antegene, Astellas, Checkmate, Gan & Lee, GlycoNex, InstilBio, Intensity, Istari, Kadmon, Kartos, NeoImmune, NGM, OncoSec, Sound Bio, SpringBank, Takeda; has received payment for advisory board roles from Merck, BMS, Pfizer, Takeda, Sanofi, Eisai. DB, DM, EN, JB, J-MN, JPS, MMP, NH, RB, SF are or were employees of Adaptimmune at the time of the study. GRB has received grants/contracts from Amgen, Bayer, Adaptimmune, Elelixis, Daiichi Sankyo, GlaxoSmithKline, Immatics, Immunocore, Incyte, Kite Pharma, Macrogenics, Torque, AstraZeneca, Bristol-Myers Squibb, Celgene, Genentech, MedImmune, Merck, Novartis, Roche, Xcovery, Tmunity Therapeutics, Regeneron, Beigene, Repertoire Immune Medicines, Verastem; consulting fees from Abbvie, Adicet, Amgen, Ariad, Bayer, Clovis Oncology, AstraZeneca, Bristol-Myers Squibb, Celgene, Daiichi Sankyo, Instil Bio, Genentech, Gilead, Lilly, Janssen, MedImmune, Merck, Novartis, Roche, Tyme Oncology, Xcovery, Virogin Biotech, Maverick Therapeutics; has participated on a Data Safety Monitoring Board or Advisory Board for Virogen Biotech, Maverick Therapeutics; holds stock or stock options in Virogin Biotech; and has other financial or non-financial interests in Johnson & Johnson/Janssen (immediate family member employed). JG has been a compensated consultant or received honoraria from Bristol-Myers Squibb, Genentech, Ariad/Takeda, Loxo, Pfizer, Incyte, Novartis, Merck, Agios, Amgen, Jounce, Karyopharm, GlydeBio, Mirati, AstraZeneca, Regeneron, Oncorus, Helsinn, Array, and Clovis Oncology; has been an employee (immediate family member) with equity in Ironwood Pharmaceuticals; has received research funding from Novartis, Genentech/Roche, and Ariad/Takeda; has received institutional research support from Tesaro, Moderna, Blueprint, Scholar Rock, BMS, Array, Adaptimmune, Novartis, Genentech/Roche, Alexo and Merck. JVH has received grants/contracts from AstraZeneca, GlaxoSmithKline and Spectrum; holds royalty/licenses in Spectrum; has received consulting fees from AstraZeneca, Boehringer-Ingelheim, Catalyst, Genentech, GlaxoSmithKline, Guardant Health, Foundation medicine, Hengrui Therapeutics, Eli Lilly, Novartis, Spectrum, EMD Serono, Sanofi, Takeda, Mirati Therapeutics, BMS, BrightPath Biotherapeutics, Janssen Global Services, Nexus Health Systems, EMD Serono, Pneuma Respiratory, Kairos Venture Investments, Roche, Leads Biolabs, RefleXion; has received honoraria from Medlinker, Peerview, Nexus Health Medicine, Targeted Oncology, MJH Events; has received support for attending meetings from IASLC Targeted Therapies, IASLC World Conference on Lung Cancer; has been in a leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid for Mechanisms of Cancer Therapeutics-1 (MCT1) (Study Section – Chair). MJ has received research funding from AbbVie, Acerta, Adaptimmune, Apexigen, Array BioPharma, AstraZeneca, Atreca, BeiGene, Boehringer Ingelheim, Checkpoint Therapeutics, Corvus Pharmaceuticals, CytomX, Daiichi Sankyo, Dynavax, Lilly, EMD Serono, Genentech/Roche, Genmab, Genocea Biosciences, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Hengrui Therapeutics, Immunocore, Incyte, Janssen, Jounce Therapeutics, Kadmon Pharmaceuticals, Loxo Oncology, Lycera, Merck, Mirati Therapeutics, Neovia Oncology, Novartis, OncoMed Pharmaceuticals, Pfizer, Regeneron Pharmaceuticals, Sanofi, Seven and Eight Biopharmaceuticals, Shattuck Labs, Stem CentRx, Syndax Pharmaceuticals, Takeda Pharmaceuticals, Tarveda, University of Michigan, WindMIL, TCR2 Therapeutics, Arcus Biosciences, Ribon Therapeutics, Amgen; has held a consulting/advisory role (spouse) for Astellas, Otsuka Pharmaceuticals; has held a consulting/advisory role (self) for AbbVie, Achilles Therapeutics, AstraZeneca, Atreca, Boehringer Ingelheim, Calithera Biosciences, Genentech, GlaxoSmithKline, Gritstone Oncology, Guardant Health, Incyte, Janssen, Lilly, Loxo Oncology, Merck, Mirati Therapeutics, Novartis, Pfizer, Ribon Therapeutics, Sanofi, Association of Community Cancer Center; has received food/beverage/travel expenses from Abbvie, Astellas, AstraZeneca, Boehringer Ingelheim, Clovis, Daiichi Sankyo, EMD Serono, Bristol Myers Squibb, Exelixis, Genentech/Roche, Incyte, Merck, Pfizer, Sysmex Inostics, Vapotherm, Janssen, Lilly, Novartis, Sanofi. MJE has received research funding from GlaxoSmithKline, Mersana, Amgen, Windmil, Nektar, Apexigen, Adaptimmune; has received consulting fees from Kanaph, Flame; has received honoraria from Sanofi; has been a member of DSMB for AstraZeneca, Seattle Genetics, GlaxoSmithKline, Takeda; has been a consultant/on an advisory board for Windmil, Regeneron, Syndax; has been the Chair, Scientific Advisory board for Lung Cancer Foundation of America; has been the Deputy Editor of 'Lung Cancer'; has received stock options from Biomarker strategies; Creatv Biotech. MJF has been a consultant for Arcellx, BMS, Novartis, Kite, Iovance. PMF is an employee of Adaptimmune; holds stock in Adaptimmune and Bristol-Myers Squib; has received compensation for travel and congress meetings. RG has received consulting fees from BMS, Abbvie, Geneplus; has participated on a Data Safety Monitoring Board or Advisory Board for Roche Genentech. SD has been a consultant for Jacobio pharmaceuticals (without financial compensation). TH was an employee of Adaptimmune at the time of the study; has been a consultant for Adaptimmune. VKL has been in a consulting or advisory role for Takeda, Bristol-Myers Squibb, Seattle Genetics; has received research funding from GlaxoSmithKline, Bristol-Myers Squibb, Guardant Health, Takeda. VM has received consulting fees from Roche, Bayer, Pieris, BMS, Janssen and Basilea. BDdS, CB, ZW have nothing to declare., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)