In this paper, we describe how swift trust in human-robot (HR) teams is developed through the incorporation of surface-level cues and imported information. Surface-level cues are physical ...characteristics whereas imported information serves to shape preconceived notions about the robot itself. A multidimensional continuum is used to explore the effects of varying surface-level cues and imported information on the type of swift trust that may form as a result: high, medium, and low swift trust. Similar surface cues and positive information suggest higher swift trust development, whereas, negative imported information and differing surface cues evoke low swift trust. Surface cues and imported information that are incongruous leads to medium swift trust formation. This paper offers insights into the development of swift trust depending on the specific traits relevant to both the human and robot team members.
With the influx of technology use and human-robot teams, it is important to understand how swift trust is developed within these teams. Given this influx, we plan to study how surface cues (i.e., ...observable characteristics) and imported information (i.e., knowledge from external sources or personal experiences) effect the development of swift trust. We hypothesize that human-like surface level cues and positive imported information will yield higher swift trust. These findings will help the assignment of human robot teams in the future.
In this trial we compared the hypothermia avoidance abilities of the Arctic Sun Temperature Management System (a servo-regulated system that circulates temperature-controlled water through unique ...energy transfer pads adherent to the patient's body) with conventional temperature control methods. Patients undergoing off-pump coronary artery bypass (OPCAB) surgery were randomized to either the Arctic Sun System alone (AS group) or conventional methods (control group; increased room temperature, heated IV fluids, convective forced air warming system) for the prevention of hypothermia (defined by a temperature <36 degrees C). The AS group had nasopharyngeal temperature servo-regulated to a target of 36.8 degrees C. Temperature was recorded throughout the operative period and comparisons were made between groups for both the time and area under the curve (AUC) for a temperature <36 degrees C (AUC<36 degrees C). Twenty-nine patients (AS group = 14, control group = 15) were studied. The AS group had significantly less hypothermia than the control group, both for duration of time <36 degrees C (2.5 0-22 min, median interquartile range AS group versus 118 49-192 min, control group; P = 0.0008) as well as for AUC<36 degrees C (0.3 0-2.2 degrees C x min, AS group versus 17.1 3.6-173.4 degrees C x min, control group; P = 0.002). The Arctic Sun Temperature Management System significantly reduced intraoperative hypothermia during OPCAB surgery. Importantly, this was achieved in the absence of any other temperature modulating techniques, including the use of IV fluid warming or increases in the ambient operating room temperature.
The Arctic Sun Temperature Management System was more effective than conventional methods in preventing hypothermia during off-pump coronary artery bypass graft surgery.
Background:
FDG PET-CT can assess bone, bone marrow and extramedullary disease (EMD) in multiple myeloma (MM), can identify disease missed through patchy marrow infiltration and complement ...established markers of adverse prognosis. The evolving definition of ‘PET-CT high-risk disease’ includes the presence of EMD and paramedullary involvement which are associated with inferior outcome. Other potential factors include SUV max >4.2 at baseline, < complete metabolic response (CMR) after autograft and >3 FDG avid focal lesions (FL).
Methods:
In the CARDAMON study, newly diagnosed MM patients eligible for ASCT received KCd (Carfilzomib, cyclophosphamide and dexamethasone) induction and either KCd consolidation or ASCT, then K maintenance for 18 cycles. In a consenting subgroup of patients, FDG PET-CT was performed at baseline, 14-28 days after completing consolidation or 100 days post-ASCT, and after 6 months maintenance. PET-CT scans were independently reviewed by 2 readers with PET positive lesions defined as uptake within focal lesions (FL) and/or diffuse marrow uptake > liver. A CMR required a Deauville score (DS) of 1-3 in FL and bone marrow.
Results:
Of 31 patients registered to the sub-study, 28 had available PET data and are included in this analysis, 61% male, median age 60 years (range 36-69). 14 patients had standard risk disease, 10 had isolated 1p-/1q+ and 4 had genetically HR disease (t(4;14), t(14;16), t(14;20) or del17p > 50% cells). Revised International Staging System (R-ISS) was I in 5/28, R-ISS II or III in 20/28 (unknown in 3/28).
Baseline PET was positive (PP) in 21/28 patients (77.8%), negative (NP) in 6/28 (22.2%) and 1 patient had a baseline scan that was not evaluable. Of the PP group, 3 had diffuse disease only, 13 had focal disease only and 5 had both focal and diffuse disease. The focal and diffuse pattern was most frequently seen in PP patients with genetic HR disease.
Median SUV max of FL in PP patients was 5.78 (range 2.19-12.93). 9/21 PP patients had >3 FL with uptake > liver at baseline and 19/21 had bone marrow DS >3. Patients with >3 FL had significantly worse PFS than those with ≤3 (HR = 5.41 (95% CI 1.05-27.9), p=0.04). There was a trend for higher presenting bone marrow trephine plasma cell involvement in PP patients at baseline (median PP 50% range 15-85), median NP 20% range 1-70) (p=0.07). PET-CT was positive at baseline in 4/5 R-ISS I patients and 15/21 R-ISS II/III. Three out of 4 patients with HR disease and evaluable scans had positive baseline PET-CTs; 1 with focal disease only and 2 with focal and diffuse disease.
Of 16 patients who underwent 2 nd PET, 12 showed CMR and 1 partial metabolic response (PMR). Four patients withdrew before assessment, 3 for progressive disease and 1 death, and 3 patients had no FDG avid lesions at baseline and post-induction. Further analysis of patients with CMR showed 1 CR and minimal residual disease negative, (MRD-ve), 7 VGPR (4 MRD+ve, 3 MRD-ve) and 4 PR (2 MRD+ve, 2 MRD-ve). The 1 patient with PMR had a VGPR (MRD-ve).
A further 11 patients underwent PET 6 months post maintenance of whom 5 remained in CMR and 5 were PET negative at baseline and response. Serological responses in the patients in CMR were 1 sCR (MRD-ve), 1 CR (MRD-ve) and 3 VGPR (1 MRD+ve, 2 MRD-ve).
With a median follow-up of 2.3 years, median progression free survival (PFS) for patients in the sub-study has not yet been reached, compared to a median PFS for the whole cohort of 3.3 years (95% CI 2.8-N/A). Median overall survival (OS) is awaited, for both groups. In the PP group, 2-year PFS was 65.6% (95% CI 41.0-82.0) vs 100% (95% CI N/A) for NP group, however due to small numbers and limited follow-up this difference was not significant (p=0.2).
Conclusions:
In the CARDAMON PET sub-study over 75% of patients had a positive baseline PET. This group had heavier marrow burden, with predominant focal disease. Patients with focal disease and >3 FL with uptake >liver had a significantly worse PFS. Follow-up PET scans for those available for response assessment showed high rates of CMR (12/13, 92%) with variable depth of serological response and MRD. Overall, K maintenance sustained PET negativity at 6 months in 10/11 patients who underwent a 3rd scan. PET is a valuable addition to disease response measures; further work will clarify the role of increased monitoring and therapeutic adaptation in PET defined high-risk groups.
Popat: GlaxoSmithKline: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; AbbVie, BMS, Janssen, Oncopeptides, and Amgen: Honoraria; Abbvie, Takeda, Janssen, and Celgene: Consultancy; Janssen and BMS: Other: travel expenses. Ramasamy: Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive biotech: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Conference registration, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Conference registration, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Conference registration, Research Funding; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene (BMS): Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Conference registration, Research Funding; Pfizer oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Streetly: BMS-Celgene: Consultancy; Sanofi: Consultancy; EUSA Pharma: Consultancy. Eccersley: Wolters-Kluwer: Honoraria. Clifton-Hadley: Amgen: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Pfizer: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Janssen-Cilag: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Merck Sharp and Dohme: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Celgene: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Millennium pharmaceutics inc.: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Bristol-Myers Squibb Pharmaceuticals Ltd..: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.. Barrington: Bristol Myers Squibb international corporation: Research Funding; Pfizer Inc: Research Funding; Amgen Ltd: Research Funding; Takeda Speakers Bureau: Honoraria. Yong: Janssen: Honoraria, Research Funding; Sanofi: Honoraria, Research Funding; Autolus: Research Funding; Takeda: Honoraria; GSK: Honoraria; Amgen: Honoraria; BMS: Research Funding.
Background: Upfront ASCT for NDTE MM continues to be challenged as standard of care due to high MRD neg rates following novel induction and consolidation (cons) strategies. The Cardamon study ...reported that KCd consolidation did not meet the statistical boundary for non-inferiority to ASCT following KCd induction, however the margin was small, with no benefit for MRD negative pts. For this analysis we focussed on the outcomes according to cytogenetic risk.
Methods: NDTE pts received 4 x KCd induction (K 20/56 mg/m 2 biweekly, C 500 mg D 1,8,15, d 40 mg weekly) before 1:1 randomisation to ASCT or 4 x KCd cons. All received 18 months K maintenance (56mg/m 2 D1,8,15). High risk (HR) was defined as any one of the HR cytogenetic abnormalities (CA) del(17p) (≥50%), t(4;14), t(14;16), t(14;20), ultraHR (uHR) as ≥2 of the HR CA, 1p- or 1q+, and standard risk (SR) as neither HR nor uHR. CA were identified by FISH on CD138 enriched cells. Subgroup analyses evaluated the impact of each single CA, including t(11;14). Flow cytometric MRD (10 -5) was assessed post induction, pre-maintenance and after 6 months maintenance, on ITT basis. The primary objective of this analysis was outcomes according to cytogenetic risk, including the impact of treatment arm.
Results: Of 281 pts registered, 259 were included with complete FISH data, 52 (20%) had HR CA, and 41 (16%) were uHR. Post induction, ≥VGPR rate was 60% in HR pts, 56% in uHR pts, and 59% in SR pts. MRD neg rates were 23%, 27% and 23% and increased to 53%, 56% and 45% with ASCT and 27%, 27% and 32% with Cons, for HR, uHR and SR respectively.
With a median follow-up of 2.8 years, the observed 2-year PFS from randomisation for ASCT was 76.6% vs 68.8% for cons (HR: 0.77 (70% CI 0.61, 0.97), p=0.2); calculated difference in 2-year PFS rate (cons vs ASCT) was -6.2% (70% CI -10.7%, -0.1%, not non-inferior).
HR and uHR pts had inferior outcomes to SR overall, with 2-year PFS rates of 49%, 50% and 76% respectively (HR vs SR: HR=2.58, p<0.001, uHR vs SR: HR=3.04, p<0.001). This was true regardless of randomisation, with 2-year PFS rates from randomisation of 61%, 63% and 80% with ASCT (HR vs SR: HR=3.27, p=0.002, uHR vs SR: HR=4.24, p<0.001) compared to 44%, 41% and 75% with cons (HR vs SR: HR=3.22, p<0.001, uHR vs SR: HR=4.11, p<0.001). Early relapse (within 18 months of registration) rate in HR and uHR was 38% and 32% vs 15% in SR (p=0.001, p=0.02 respectively). There was no evidence of a statistically significant PFS benefit for ASCT over cons in the HR, uHR or SR subgroups with HRs of 0.77 (p=0.5), 0.81 (p=0.5) and 0.81 (p=0.6) respectively.
Analysis by single CA was limited by the small pt numbers in each group, however pts with t(4;14) had worse PFS (HR: 2.62, p<0.01) than those without t(4;14), similarly with del(17p) (≥50%) (HR: 3.57, p<0.01) and 1p- (HR: 2.76, p<0.01).
While numbers are small and the interaction does not meet significance (p=0.16), pts with t(11;14) tended to demonstrate a benefit for ASCT over cons (2-year PFS 89% vs 67%).
Conclusions: HR or uHR pts receiving KCd induction, followed by ASCT or KCd cons, had a significantly shorter PFS compared to SR pts. Consolidation with KCd did not meet the boundary for non-inferiority to ASCT, though the margin is small and none of the HR, uHR and SR cytogenetic risk groups had a statistically significant PFS benefit with ASCT.
Yong: GSK: Honoraria; Takeda: Honoraria; Janssen: Honoraria, Research Funding; BMS: Research Funding; Amgen: Honoraria; Sanofi: Honoraria, Research Funding; Autolus: Research Funding. Ramasamy: Karyopharm: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer oncology: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene (BMS): Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Conference registration, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Conference registration, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Conference registration, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel, Conference registration, Research Funding; Adaptive biotech: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees. Streetly: BMS-Celgene: Consultancy; Sanofi: Consultancy; EUSA Pharma: Consultancy. Clifton-Hadley: Bristol-Myers Squibb Pharmaceuticals Ltd..: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Amgen: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Celgene: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Merck Sharp and Dohme: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Janssen-Cilag: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Pfizer: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.; Millennium pharmaceutics inc.: Other: The haematology team at the CTC has received funding (which in part pays staff salary) to Sponsor and coordinate clinical trials.. Popat: GlaxoSmithKline: Consultancy, Honoraria, Research Funding; AbbVie, BMS, Janssen, Oncopeptides, and Amgen: Honoraria; Abbvie, Takeda, Janssen, and Celgene: Consultancy; Takeda: Honoraria, Other: TRAVEL, ACCOMMODATIONS, EXPENSES; Janssen and BMS: Other: travel expenses.
Human-Robot Teams: A Discussion of the Emerging Trends Patel, Sabina M.; Rosero, Andres; Lazzara, Elizabeth H. ...
Proceedings of the Human Factors and Ergonomics Society Annual Meeting,
09/2022, Volume:
66, Issue:
1
Journal Article
Peer reviewed
As technology advances, human robot-teams are becoming increasingly commonplace with team interactions taking place in a variety of military, industrial, service, and social settings. Consequently, ...as HR teams evolve, novel and unique considerations for how these teams interact and perform are rising. The purpose of this panel, therefore, is to host a discussion on state-of-theart issues and emerging trends that practitioners and researchers should scrutinize as the applications of HR teams expands. To provide a diverse set of perspectives, our panelists hail from a variety of backgrounds: military, industry, and academy. Talks will focus on moral and ethical considerations for human-agent decision-making, the influence of robots on team processes in human surgical teams, and on new considerations for trust in human-agent teams, including for covert measures of trust and for the inclusion of team cohesion in trust measurement.
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Background. BL is a rare, high-grade B-cell lymphoma that is often studied in trials with small sample sizes. Historical definitions of “low-risk BL” vary between studies, use arbitrary cutoffs for ...lactate dehydrogenase (LDH), and identify a small favorable group, leaving >80-90% of patients (pts) in an undifferentiated “high-risk” category. A validated prognostic index will help compare study cohorts and better define good-prognosis pts for whom reduced treatment would be appropriate vs a poor-prognosis group in need of new approaches. Herein, we constructed and validated a simplified prognostic model for BL applicable to diverse clinical settings across the world.
Methods. We derived the BL-IPI from a large real-world evidence cohort of US adults treated for BL in 2009-2018 (Evens A, Blood 2020). Progression-free survival (PFS) from diagnosis until BL recurrence, progression, death, or censoring was the primary outcome. We first determined the best prognostic cutoffs for age, LDH (normalized to local upper limit normal, ULN), hemoglobin (Hgb), and albumin. Independent risk factors were ascertained by forward stepwise selection into Cox regression from candidate variables: age, sex, HIV+ status, ECOG performance status (PS) ≥2, advanced stage (3/4), involvement of >1 extranodal site, bone marrow, central nervous system (CNS), values of LDH, Hgb, and albumin. Derivation models used multiple imputation to mitigate bias from missing data and reported hazard ratios (HR) with 95% confidence interval (CI). BL-IPI groups, defined by inspection of survival curves, were compared using log-rank test for trend. We validated performance of the BL-IPI in an external retrospective dataset of BL pts treated contemporaneously in centers from the United Kingdom, Scandinavia, Canada, and Australia.
Results. Characteristics of pts in the derivation (N= 633) and validation (N=457) cohorts are shown in the Table. Age ≥40 years (yr), LDH >3xULN, Hgb <11.5 g/dL, and albumin <3.5 g/dL were determined as optimal prognostic cutoffs. Age ≥40 yr, PS ≥2, stage 3/4, involvement of marrow, CNS, LDH >3xULN, low Hgb, and low albumin were associated with inferior PFS in univariate tests. In the multivariable model age ≥40 yr, LDH >3xULN, PS ≥2, and CNS involvement were selected as 4 independent prognostic factors; adding stage did not enhance the model. The model was simplified to 3 groups with 0 (low risk; 18% of pts), 1 (intermediate risk; 36% of pts; HR=3.14; 95%CI, 1.61-6.14), or 2-4 factors (high risk; 46% of pts; HR=6.52; 95%CI, 3.48-12.20; Fig A) with 3 yr PFS of 92%, 72%, and 53%, respectively (P<.001, Fig. B); median PFS was reached only in the high-risk group (46 months, 95%CI, 19-53). BL-IPI was similarly prognostic for overall survival (OS, P<.001; Fig. C).
Among pts with stage III/IV (historically classified as “high-risk” and constituting 78% of all pts in the cohort), the BL-IPI further discriminated subgroups with 3 yr PFS of 87%, 71%, and 52%, respectively (P<.001; Fig. D), and OS of 95%, 75%, and 57%, respectively (P<.001; Fig. E). In addition, BL-IPI was prognostic regardless of HIV status, in the subcohort treated with rituximab (3 yr PFS: 92%, 73%, and 55%, respectively, P<.001), and among pts treated with specific regimens: CODOX-M/IVAC±R (3 yr PFS: 88%, 67%, 61%, respectively, P=.004), DA-EPOCH-R (3 yr PFS, 87%, 73%, 51%, respectively, P<.001), or hyperCVAD/MA±R (3yr PFS: 100%, 80%, 54%, respectively, P<.001).
In the international validation cohort, fewer pts had CNS involvement; most received CODOX-M/IVAC+R; and PFS/OS estimates at 3 yr were higher. BL-IPI categories were of similar size (low-risk 15%, intermediate-risk 35%, high-risk 50%), and provided similar risk discrimination (Harrell’s C=.65 in both datasets). PFS at 3 yr was 96%, 82%, and 63%, respectively (P<.001; Fig. F), and OS was 99%, 85%, and 64%, respectively (P<.001; Fig. G). In the validation cohort, BL-IPI remained prognostic in the subsets receiving rituximab (P<.001) and in advanced stage (P<.001).
Conclusions. BL-IPI is a novel prognostic index specific to BL, which was validated to allow for simplified stratification and comparison of risk distribution in geographically diverse cohorts. The index identified a low-risk group with PFS >90-95%, which could be targeted with future strategies for treatment de-escalation. Conversely, only about 55-60% of pts in the high-risk group achieved cure with currently available immunochemotherapy.
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Olszewski:Spectrum Pharmaceuticals: Research Funding; Genentech, Inc.: Research Funding; TG Therapeutics: Research Funding; Adaptive Biotechnologies: Research Funding. Jakobsen:Takeda: Honoraria. Collins:ADC Therapeutics: Consultancy, Honoraria; Celleron: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Speakers Bureau; Amgen: Research Funding; BeiGene: Consultancy; BMS: Consultancy, Honoraria, Research Funding, Speakers Bureau; Gilead: Consultancy, Honoraria, Speakers Bureau; MSD: Consultancy, Honoraria, Research Funding; Taekda: Consultancy, Honoraria, Other: travel, accommodations, expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Other: travel, accommodations, expenses , Speakers Bureau; Pfizer: Honoraria; Celgene: Research Funding. Cwynarski:Janssen: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Support; Atara: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Gilead: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Speakers Bureau; KITE: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Takeda: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau; Celgene: Consultancy, Membership on an entity’s Board of Directors or advisory committees; Roche: Consultancy, Membership on an entity’s Board of Directors or advisory committees, Other: Travel Support, Speakers Bureau. Bachanova:Incyte: Research Funding; Karyopharma: Membership on an entity’s Board of Directors or advisory committees; BMS: Research Funding; FATE: Research Funding; Kite: Membership on an entity’s Board of Directors or advisory committees; Gamida Cell: Membership on an entity’s Board of Directors or advisory committees, Research Funding. Danilov:Abbvie: Consultancy; BeiGene: Consultancy; Nurix: Consultancy; Celgene: Consultancy; Gilead Sciences: Research Funding; Takeda Oncology: Research Funding; Pharmacyclics: Consultancy; Bayer Oncology: Consultancy, Research Funding; Genentech: Consultancy, Research Funding; TG Therapeutics: Consultancy; Astra Zeneca: Consultancy, Research Funding; Verastem Oncology: Consultancy, Research Funding; Karyopharm: Consultancy; Aptose Biosciences: Research Funding; Bristol-Myers Squibb: Research Funding; Rigel Pharmaceuticals: Consultancy. Diefenbach:Trillium: Research Funding; Millenium/Takeda: Research Funding; MEI: Research Funding; Merck: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Genentech, Inc.: Consultancy, Research Funding; Incyte: Research Funding; LAM Therapeutics: Research Funding; Denovo: Research Funding. Epperla:Pharmacyclics: Honoraria; Verastem Oncology: Speakers Bureau. Farooq:Kite, a Gilead Company: Honoraria. Feldman:Pfizer: Research Funding; Portola: Research Funding; Janssen: Speakers Bureau; AstraZeneca: Consultancy; Cell Medica: Research Funding; Seattle Genetics, Inc.: Consultancy, Honoraria, Other: Travel expenses, Research Funding, Speakers Bureau; Viracta: Research Funding; Trillium: Research Funding; Rhizen: Research Funding; Corvus: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Kite: Honoraria, Other: Travel expenses, Speakers Bureau; Celgene: Honoraria, Research Funding; Takeda: Honoraria, Other: Travel expenses; Amgen: Research Funding; Pharmacyclics: Honoraria, Other, Speakers Bureau; Abbvie: Honoraria; Bayer: Consultancy, Honoraria; Eisai: Research Funding; Kyowa Kirin: Consultancy, Research Funding. Gerrie:AbbVie: Consultancy, Honoraria, Research Funding; Astrazeneca: Consultancy, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Roche: Research Funding; Sandoz: Consultancy. Jagadeesh:Regeneron: Research Funding; Seattle Genetics: Membership on an entity’s Board of Directors or advisory committees, Research Funding; Debiopharm Group: Research Funding; MEI Pharma: Research Funding; Verastem: Membership on an entity’s Board of Directors or advisory committees. Kamdar:BMS: Consultancy; Abbvie: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy; Pharmacyclics: Consultancy; Seattle Genetics: Speakers Bureau. Karmali:Takeda: Research Funding; AstraZeneca: Speakers Bureau; BeiGene: Speakers Bureau; Karyopharm: Honoraria; BMS/Celgene/Juno: Honoraria, Other, Research Funding, Speakers Bureau; Gilead/Kite: Honoraria, Other, Research Funding, Speakers Bureau. Khan:Seattle Genetics: Research Funding; Janssen: Honoraria; Pharmacyclics: Honoraria; Bristol Myers Squibb: Research Funding; Celgene: Research Funding. Klein:Takeda: Membership on an entity’s Board of Directors or advisory committees. Lossos:Verastem: Consultancy, Honoraria; Stanford University: Patents & Royalties; Seattle Genetics: Consultancy, Other; Janssen Biotech: Honoraria; NCI: Research Funding; Janssen Scientific: Consultancy, Other. Lunning:ADC Therapeutics: Consultancy; Legend: Consultancy; Acrotech: Consultancy; AstraZeneca: Consultancy, Honoraria; Aeratech: Consultancy, Honoraria; Beigene: Consultancy, Honoraria; Verastem: Consultancy, Honoraria; TG Therapeutics: Research Funding; Novartis: Consultancy, Honoraria; Kite: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Gilead: Consultancy, Honoraria; Curis: Research Funding;
Summary
CD19 CAR‐T have emerged as a new standard treatment for relapsed/refractory (r/r) large B‐cell lymphoma (LBCL). CAR‐T real‐world (RW) outcomes published to date suggest significant ...variability across countries. We provide results of a large national cohort of patients intended to be treated with CAR‐T in the UK. Consecutive patients with r/r LBCL approved for CAR‐T by the National CAR‐T Clinical Panel between December 2018 and November 2020 across all UK CAR‐T centres were included. 404/432 patients were approved 292 axicabtagene ciloleucel (axi‐cel), 112 tisagenlecleucel (tisa‐cel), 300 (74%) received the cells. 110/300 (38.3%) patients achieved complete remission (CR) at 6 months (m). The overall response rate was 77% (52% CR) for axi‐cel, 57% (44% CR) for tisa‐cel. The 12‐month progression‐free survival was 41.8% (axi‐cel) and 27.4% (tisa‐cel). Median overall survival for the intention‐to‐treat population was 10.5 m, 16.2 m for infused patients. The incidence of grade ≥3 cytokine release syndrome and neurotoxicity were 7.6%/19.6% for axi‐cel and 7.9%/3.9% for tisa‐cel. This prospective RW population of CAR‐T eligible patients offers important insights into the clinical benefit of CD19 CAR‐T in LBCL in daily practice. Our results confirm long‐term efficacy in patients receiving treatment similar to the pivotal trials, but highlight the significance of early CAR‐T failure.
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