scholarly journals Prognostic Impact of Metabolic Tumor Burden in Large B-Cell Lymphoma Patients Receiving CAR T-Cell Therapy

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-29
Author(s):  
Gloria Iacoboni ◽  
Marc Simo ◽  
Guillermo Villacampa ◽  
Eva Catala ◽  
Cecilia Carpio ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell Lymphoma ◽  
Tumor Burden ◽  
T Cell Therapy ◽  
Disease Response ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Metabolic Tumor Burden

Introduction Chimeric antigen receptor (CAR) T-cell therapy provides long-term remissions in a substantial proportion of patients with large B-cell lymphoma (LBCL) who have relapsed or are refractory (R/R) to chemoimmunotherapy. The identification of prognostic factors to identify which patients will benefit most from this therapy is crucial to improve patient selection. Even though metabolic tumor burden assessed by 18F-fluorodeoxyglucose Positron Emission Tomography (PET) has a confirmed prognostic value in the setting of chemoimmunotherapy, its predictive role after CAR T-cell therapy is not established. Methods We conducted a single-center study including all patients with R/R LBCL who received a single infusion of CD19-targeted second-generation CAR T-cells carrying a 4-1BB costimulatory domain from July 2018 to January 2020. Adverse events were graded according to the American Society for Transplantation and Cellular Therapy (ASTCT) consensus. All patients underwent a baseline PET scan and metabolic disease evaluation after infusion. Disease response assessment was conducted according to Lugano criteria. Metabolic tumor volume (MTV) and maximum standardized uptake value (SUVmax) were measured at baseline and at 1-month after CAR T-cell infusion, and correlated with disease response and development of adverse events. To identify the optimal cut-offs for metabolic parameters we used the maximally selected log-rank statistics in the PFS analysis. Results Thirty-five consecutive patients with R/R LBCL who received CAR T-cell therapy were included in the study. Patients' baseline characteristics are summarized in Table 1. Median age at treatment was 58 years, and 74% were males. At the time of diagnosis most of them had an advanced stage of disease (86%) and were refractory to the last therapy (n=31, 88%). Best response after CAR T-cell therapy included 9 (26%) patients in complete remission (CR) and 16 (46%) in partial remission (PR). Ten (28%) patients were in progressive disease (PD) at the 1-month disease evaluation. At a median follow-up of 7.6 months, median PFS and OS were 3.4 months and 8.2 months, respectively. Regarding toxicity, eleven (31%) patients developed clinically significant CAR T-cell related toxicity, defined as grade 2 or higher CRS (n=7, 20%) and grade 2 or higher ICANS (n=6, 17%). Median baseline MTV and MTV41% were 270 cm3(IQR 87-875) and 119 cm3 (IQR 32-300), respectively. Median SUVmax was 24 (IQR 17-32). Patients who responded (CR and PR) had lower baseline MTV values compared with non-responders (median of 228 cm3 vs 645 cm3, p=0.04) (Figure 1a). No association was found between MTV41% or SUVmax and disease response. In terms of PFS, a high baseline MTV (>82 cm3) was associated with a lower PFS compared to patients with lower MTV values (median PFS, 2.1 months vs. 6 months; HR 3.15, p= 0.02) (Table 2 and Figure 2). Patients with high baseline MTV41% values (>25 cm3) also had an inferior PFS (HR 3.44, p= 0.02); no association was found between baseline SUVmax and PFS (Table 2). As per OS, there was no significant association with baseline MTV, MTV41% and SUVmax (Table 2). Regarding toxicity, there was no significant association between baseline MTV, MTV 41% and SUVmax values with grade 2 or higher CRS and ICANS events (Figure 1b). All patients underwent a 1-month post-infusion PET evaluation. Disease response at this timepoint was: CR in 8 patients (23%), PR in 17 patients (49%) and PD in 10 patients (28%). For patients in CR and PR at 1-month the probability of PFS at 6 months was 62.5% and 12.7%, respectively (HR=3.89, p=0.02). For patients in PR at the 1-month evaluation, MTV values at that timepoint were predictive for PFS; patients in PR with low (<35 cm3) and high 1-month MTV values had a 6m-PFS of 33% and 0%, respectively (Figure 3)(HR=4.6, p = 0.01). In these patients, SUVmax values also predicted PFS and a trend towards significance was observed for MTV41% (HR=3, p=0.07). Conclusion Metabolic tumor burden parameters measured by 18FDG-PET before and 1-month after CAR-T cell infusion identify LBCL patients who benefit most from these therapies and could aid patient selection. Disclosures Iacoboni: Novartis, Gilead, Celgene, Roche: Honoraria. Villacampa:AstraZeneca: Other: advisory role; Merck Sharp & Dohme: Honoraria. Abrisqueta:AbbVie: Consultancy, Honoraria, Speakers Bureau; Janssen: Consultancy, Honoraria, Speakers Bureau; Celgene: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Speakers Bureau. Bosch:Hoffmann-La Roche: Research Funding. Barba:Novartis, Celgene, Gilead, Pfizer, Amgen, Roche: Honoraria.

scholarly journals Potential strategies against resistance to CAR T-cell therapy in haematological malignancies

2020 ◽  
Vol 12 ◽  
pp. 175883592096296
Author(s):  
Qing Cai ◽  
Mingzhi Zhang ◽  
Zhaoming Li
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell Lymphoma ◽  
Complete Response ◽  
Haematological Malignancies ◽  
T Cell Therapy ◽  
Cell Therapies ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Chimeric antigen receptor (CAR) T-cell therapy is a rapidly developing method for adoptive immunotherapy of tumours in recent years. CAR T-cell therapies have demonstrated unprecedented efficacy in the treatment of patients with haematological malignancies. A 90% complete response (CR) rate has been reported in patients with advanced relapse or refractory acute lymphoblastic leukaemia, while >50% CR rates have been reported in cases of chronic lymphocytic leukaemia and partial B-cell lymphoma. Despite the high CR rates, a subset of the patients with complete remission still relapse. The mechanism of development of resistance is not clearly understood. Some patients have been reported to demonstrate antigen-positive relapse, whereas others show antigen-negative relapses. Patients who relapse following CAR T-cell therapy, have very poor prognosis and novel approaches to overcome resistance are required urgently. Herein, we have reviewed current literature and research that have investigated the strategies to overcome resistance to CAR T-cell therapy.

Anakinra (AKR) prophylaxis (ppx) in patients (pts) with relapsed/refractory multiple myeloma (RRMM) receiving orvacabtagene autoleucel (orva-cel).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 2537-2537
Author(s):  
Luciano J. Costa ◽  
Sham Mailankody ◽  
Paul Shaughnessy ◽  
Parameswaran Hari ◽  
Jonathan L. Kaufman ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Phase 1 ◽  
Median Number ◽  
Control Group ◽  
T Cell Therapy ◽  
Disease Response ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

2537 Background: Orva-cel is a B-cell maturation antigen–targeted chimeric antigen receptor (CAR) T cell therapy being evaluated in the phase 1/2 EVOLVE study (NCT03430011) in pts with RRMM who had at least 3 prior lines of therapy (Tx). We previously reported safety and efficacy in the phase 1 study and established the recommended dose (RD) of orva-cel as 600 × 106 CAR+ T cells (Mailankody et al, ASCO 2020). Cytokine release syndrome (CRS), a dominant toxicity of CAR T cell therapy, is mediated in part by IL-1. We explore the role of ppx with AKR, an IL-1 signaling inhibitor, on reducing the incidence of grade (G) ≥2 CRS after orva-cel treatment at the RD. Methods: Fourteen pts were enrolled sequentially for AKR ppx and treated with orva-cel at the RD. The non-AKR ppx control group comprised the remainder of the phase 1 pts receiving orva-cel at the RD (n = 19). The median follow-up (range) was 3.0 mo (1.8–6.2) for the AKR ppx group and 8.8 mo (5.3–12.2) for the non-AKR ppx group. AKR was administered as 100 mg SC the night before orva-cel infusion, 3 h before the infusion (Day 1), and q24 h on Days 2–5. Dosing was increased to q12 h if CRS developed. CRS was graded by Lee (2014) criteria. Tocilizumab (T) and steroids (S) were used per protocol-specified treatment management guidelines. Results: Disease characteristics and outcomes are shown in the table. In AKR ppx and non-AKR ppx groups, median number of prior regimens was 6 and 5, and bridging Tx was used in 57% and 68% of pts, respectively. The total frequency of CRS was similar in the 2 groups, but with less G 2 in the AKR ppx pts; relative risk (95% CI) = 0.54 (0.21, 1.38). No G ≥3 CRS was seen in either group. The incidence of neurological events (NE), G ≥3 infection, and macrophage activation syndrome/hemophagocytic lymphohistiocytosis (MAS/HLH) was similar. T and S use was numerically lower with AKR ppx. Orva-cel expansion kinetics were similar in the 2 groups. All pts had a 2-month efficacy assessment, with ORR in 100% of AKR ppx and 95% of non–AKR ppx pts. Conclusions: In this nonrandomized evaluation of AKR ppx with orva-cel treatment, the incidence of G ≥2 CRS was lower in pts receiving AKR ppx. The use of AKR ppx produced no adverse effect on the incidence of NE, infection, or MAS/HLH, nor on orva-cel expansion or disease response. These results warrant further study of AKR ppx in CAR T cell therapy. Clinical trial information: NCT03430011. [Table: see text]

scholarly journals Influence of TP53 Mutation on Survival of Diffuse Large B-Cell Lymphoma in the CAR T-Cell Era

Cancers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 5592
Author(s):  
Edit Porpaczy ◽  
Philipp Wohlfarth ◽  
Oliver Königsbrügge ◽  
Werner Rabitsch ◽  
Cathrin Skrabs ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell ◽  
Tp53 Mutation ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Refractory/relapsed diffuse large B-cell lymphoma (DLBCL) is associated with poor outcome. The clinical behavior and genetic landscape of DLBCL is heterogeneous and still not fully understood. TP53 mutations in DLBCL have been identified as markers of poor prognosis and are often associated with therapeutic resistance. Chimeric antigen receptor T-cell therapy is an innovative therapeutic concept and represents a game-changing therapeutic option by supporting the patient’s own immune system to kill the tumor cells. We investigated the impact of TP53 mutations on the overall survival of refractory/relapsed DLBCL patients treated with comparable numbers of therapy lines. The minimum number of therapy lines was 2 (median 4), including either anti-CD19 CAR T-cell therapy or conventional salvage therapy. A total of 170 patients with DLBCL and high-grade B-cell lymphoma with MYC, BCL2, and/or BCL6 rearrangements (DHL/THL), diagnosed and treated in our hospital between 2000 and 2021, were included. Twenty-nine of them received CAR T-cell therapy. TP53 mutations were found in 10/29 (35%) and 31/141 (22%) of patients in the CAR T-cell and conventional groups, respectively. Among the 141 patients not treated with CAR T cells, TP53 mutation was an independent prognostic factor for overall survival (OS) (median 12 months with TP53 vs. not reached without TP53 mutation, p < 0.005), but in the CAR T cell treated group, this significance could not be shown (median OS 30 vs. 120 months, p = 0.263). The findings from this monocentric retrospective study indicate that TP53 mutation status does not seem to affect outcomes in DLBCL patients treated with CAR T-cell therapy. Detailed evaluation in large cohorts is warranted.

Outreach: Preliminary safety and efficacy results from a phase 2 study of lisocabtagene maraleucel (liso-cel) in the nonuniversity setting.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19513-e19513
Author(s):  
John E. Godwin ◽  
Bassam Ibrahim Mattar ◽  
Michael B. Maris ◽  
Carlos R. Bachier ◽  
Don A. Stevens ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell Lymphoma ◽  
Multidisciplinary Teams ◽  
Inpatient Setting ◽  
T Cell Therapy ◽  
Safety And Efficacy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

e19513 Background: Concerns about adverse events (AEs) related to CAR T cell therapy have resulted in administration of this therapy largely in an inpatient setting. OUTREACH (NCT03744676) evaluates safety and efficacy of liso-cel in patients (pts) with R/R large B-cell lymphoma (LBCL) across inpatient and outpatient settings at nonuniversity medical centers (NMCs). Methods: NMCs, including centers naïve to CAR T cell therapy, enrolled adults with R/R LBCL in this open-label, multicenter study. Eligible pts had R/R PET-positive disease after ≥2 lines of prior systemic therapy, ECOG PS ≤1, and adequate organ function. Prior autologous HSCT was allowed. Pts received sequential infusions of equal target doses of CD8+ and CD4+ cells at a total target dose of 100 × 106 CAR+ T cells. Primary endpoint was incidence of grade (G) ≥3 cytokine release syndrome (CRS) graded per 2014 Lee criteria, neurological events (NEs), prolonged cytopenias (Day 29 G ≥3 lab values), and infections. Secondary endpoints were safety and overall response rate (ORR). Outpatient AE monitoring/management was managed by a multidisciplinary CAR T cell therapy team following standard operating procedures (SOPs). Results: At data cutoff, 46 pts (inpatients n = 16, outpatients n = 30) were treated with liso-cel. Inpatients and outpatients had similar demographics and baseline disease characteristics; median age was 63 y (range, 34–83), 63% had diffuse LBCL not otherwise specified, and 91% were refractory to last therapy. Safety data were similar across inpatients and outpatients (Table). Early (study Day ≤4) and overall hospitalization in outpatients was reported in 27% and 63%, respectively; median time to hospitalization was 5 (2–61) days and median length of stay was 6 (1–28) days. For efficacy-evaluable pts (n = 44), ORR was 75% for inpatients and 79% for outpatients; CR rates were 50% and 61%, respectively. Conclusions: Liso-cel was successfully administered to pts with R/R LBCL in the outpatient setting and pts were monitored for CAR T cell therapy–related toxicities by multidisciplinary teams using SOPs. The incidences of severe CRS and NEs and use of tocilizumab and/or corticosteroids were similar in inpatients and outpatients, and consistent with the pivotal study observations (Abramson, The Lancet 2020). Updated data with longer follow-up will be presented. Clinical trial information: NCT03744676. [Table: see text]

NCMP-10. DYSGRAPHIA AS THE EARLIEST PRESENTING SYMPTOM OF SEVERE CHIMERIC ANTIGEN RECEPTOR (CAR) T-CELL THERAPY NEUROTOXICITY: A SINGLE CENTER EXPERIENCE

2021 ◽  
Vol 23 (Supplement_6) ◽  
pp. vi149-vi149
Author(s):  
Carlen Yuen ◽  
Kourosh Rezania ◽  
Thomas Kelly ◽  
Michael Bishop
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Antigen Receptor ◽  
B Cell Lymphoma ◽  
Motor Dysfunction ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Abstract INTRODUCTION Chimeric antigen receptor (CAR) T-cell therapy, including axicabtagene ciloleucel (axi-cel; Yescarta®) and tisagenlecleucel (tisa-cel; Kymriah®), are FDA approved for the treatment of adult patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Neurotoxicity (NT) associated with CAR T-cell therapy (immune effector cell-associated neurotoxicity syndrome [ICANS]) can be fatal. Timely data, in the form of an abbreviated bedside mini-mental status exam, is thought to lead to earlier identification of NT. However, existing literature validating this method is limited. MATERIALS AND METHODS In this retrospective study, patients with R/R DLBCL treated with commercial axi-cel or tisa-cel in our center from December 2017 to September 2018 were assessed for NT with the CTCAE v4 criteria and the CAR-T-cell-therapy-associated TOXicity (CARTOX-10) scoring system. RESULTS Twenty-six patients with R/R DLBCL were treated with CAR T-cell therapy (25 axi-cel/[Yescarta®] and 1 tisagenlecleucel [Kymriah®]). Twenty-three (88%) developed NT with 8 (31%) experiencing severe NT (Grade III-IV). Tremor and dysgraphia occurred in all patients with severe NT. Lower average CARTOX-10 score (p=&lt; 0.01), dysgraphia (p&lt; 0.01), inattention (p=.018), and disorientation (p=.01) were significantly associated in patients with severe NT. A trend towards significance was observed between tremor and severe NT (p=.08). All patients with severe NT had both dysgraphia and tremor 8/8 (100%) and 2/8 (25%) had concurrent dysnomia. Death occurred in 12/26 (46%) of patients due to disease progression (n=11) and cardiac failure due to myositis (n=1). CONCLUSION In our limited cohort, dysgraphia, inattention, and disorientation are heralding symptoms of severe NT in adult R/R DLBCL patients treated with commercial CAR T-cell therapy. Dysgraphia was the earliest presenting symptom in patients with severe CAR T-cell neurotoxicity and was likely a manifestation of motor dysfunction rather than a component of dysphasia. Further studies with a larger cohort are needed to validate our findings.

scholarly journals DLBCL patients treated with CD19 CAR T cells experience a high burden of organ toxicities but low nonrelapse mortality

2020 ◽  
Vol 4 (13) ◽  
pp. 3024-3033 ◽  
Author(s):  
Kitsada Wudhikarn ◽  
Martina Pennisi ◽  
Marta Garcia-Recio ◽  
Jessica R. Flynn ◽  
Aishat Afuye ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Abstract Cytokine release syndrome (CRS) immune effector cell–associated neurotoxicity syndrome are the most notable toxicities of CD19 chimeric antigen receptor (CAR) T-cell therapy. In addition, CAR T-cell–mediated toxicities can involve any organ system, with varied impacts on outcomes, depending on patient factors and involved organs. We performed detailed analysis of organ-specific toxicities and their association with outcomes in 60 patients with diffuse large B-cell lymphoma (DLBCL) treated with CD19 CAR T cells by assessing all toxicities in organ-based groups during the first year posttreatment. We observed 539 grade ≥2 and 289 grade ≥3 toxicities. Common grade ≥3 toxicities included hematological, metabolic, infectious, and neurological complications, with corresponding 1-year cumulative incidence of 57.7%, 54.8%, 35.4%, and 18.3%, respectively. Patients with impaired performance status had a higher risk of grade ≥3 metabolic complications, whereas elevated lactate dehydrogenase was associated with higher risks of grade ≥3 neurological and pulmonary toxicities. CRS was associated with higher incidence of grade ≥3 metabolic, pulmonary, and neurologic complications. The 1-year nonrelapse mortality and overall survival were 1.7% and 69%, respectively. Only grade ≥3 pulmonary toxicities were associated with an increased mortality risk. In summary, toxicity burdens after CD19 CAR T-cell therapy were high and varied by organ systems. Most toxicities were manageable and were rarely associated with mortality. Our study emphasizes the importance of toxicity assessment, which could serve as a benchmark for further research to reduce symptom burdens and improve tolerability in patients treated with CAR T cells.

scholarly journals Tumor burden, inflammation, and product attributes determine outcomes of axicabtagene ciloleucel in large B-cell lymphoma

2020 ◽  
Vol 4 (19) ◽  
pp. 4898-4911 ◽  
Author(s):  
Frederick L. Locke ◽  
John M. Rossi ◽  
Sattva S. Neelapu ◽  
Caron A. Jacobson ◽  
David B. Miklos ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Tumor Burden ◽  
Durable Response ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Large B Cell Lymphoma ◽  
Car T Cell Therapy ◽  
Car T

Abstract ZUMA-1 demonstrated a high rate of durable response and a manageable safety profile with axicabtagene ciloleucel (axi-cel), an anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in patients with refractory large B-cell lymphoma. As previously reported, prespecified clinical covariates for secondary end point analysis were not clearly predictive of efficacy; these included Eastern Cooperative Oncology Group performance status (0 vs 1), age, disease subtype, disease stage, and International Prognostic Index score. We interrogated covariates included in the statistical analysis plan and an extensive panel of biomarkers according to an expanded translational biomarker plan. Univariable and multivariable analyses indicated that rapid CAR T-cell expansion commensurate with pretreatment tumor burden (influenced by product T-cell fitness), the number of CD8 and CCR7+CD45RA+ T cells infused, and host systemic inflammation, were the most significant determining factors for durable response. Key parameters differentially associated with clinical efficacy and toxicities, with both theoretical and practical implications for optimizing CAR T-cell therapy. This trial was registered at www.clinicaltrials.gov as #NCT02348216.

scholarly journals Advancing CAR T-Cell Therapy for Solid Tumors: Lessons Learned from Lymphoma Treatment

Cancers ◽  
2020 ◽  
Vol 12 (1) ◽  
pp. 125 ◽  
Author(s):  
Aleksei Titov ◽  
Aygul Valiullina ◽  
Ekaterina Zmievskaya ◽  
Ekaterina Zaikova ◽  
Alexey Petukhov ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
Solid Tumors ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Chimeric antigen receptor (CAR) immunotherapy is one of the most promising modern approaches for the treatment of cancer. To date only two CAR T-cell products, Kymriah® and Yescarta®, have been approved by the Food and Drug Administration (FDA) for the treatment of lymphoblastic leukemia and B-cell lymphoma. Administration of CAR T-cells to control solid tumors has long been envisaged as one of the most difficult therapeutic tasks. The first two clinical trials conducted in sarcoma and neuroblastoma patients showed clinical benefits of CAR T-cells, yet multiple obstacles still hold us back from having accessible and efficient therapy. Why did such an effective treatment for relapsed and refractory hematological malignancies demonstrate only relatively modest efficiency in the context of solid tumors? Is it due to the lucky selection of the “magic” CD19 antigen, which might be one of a kind? Or do lymphomas lack the immunosuppressive features of solid tumors? Here we review the existing knowledge in the field of CAR T-cell therapy and address the heterogeneity of solid tumors and their diverse strategies of immunoevasion. We also provide an insight into prospective developments of CAR T-cell technologies against solid tumors.

scholarly journals Impact of Increasing Wait Times on Overall Mortality of Chimeric Antigen Receptor T-Cell Therapy in Large B-Cell Lymphoma: A Discrete Event Simulation Model

2019 ◽  
pp. 1-9 ◽  
Author(s):  
Stephen Tully ◽  
Zeny Feng ◽  
Kelly Grindrod ◽  
Tom McFarlane ◽  
Kelvin K.W. Chan ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
B Cell Lymphoma ◽  
Wait Times ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Large B Cell Lymphoma ◽  
Car T Cell Therapy ◽  
Car T ◽  
Large B Cell

PURPOSE The development of chimeric antigen receptor (CAR) T cells has transformed oncology treatment, with the potential to cure certain cancers. Although shown to be effective in selected populations and studies, CAR T-cell technology requires considerable health care resources, which may lead to additional wait times to access this type of treatment in future. The objective of our study was to estimate the potential impact of increasing wait times on CAR T-cell therapy effectiveness compared with standard chemotherapy for patients with relapsed/refractory diffuse large B-cell lymphoma. METHODS A health system–level discrete event simulation model was developed to project the potential impact of wait times on CAR T-cell therapy for patients with relapsed/refractory diffuse large B-cell lymphoma. Waiting queues and health states related to treatment and clinical progression were implemented. Using data from the literature, we evaluated nine scenarios of using CAR T-cell therapy with wait times ranging from 1 to 9 months. The outcome of interest was 1-year all-cause mortality. RESULTS Increasing the wait time of receiving CAR T-cell therapy from 1 to 9 months increased the predicted 1-year mortality rate from 36.1% to 76.3%. Baseline 1-year mortality was 34.0% in patients receiving CAR T-cell therapy with no wait times and 75.1% in patients treated with chemotherapy. This resulted in an increased relative mortality rate of 6.2% to 124.5% over a 1- to 9-month wait time compared with no wait time. CONCLUSION We found that modest delays in CAR T-cell therapy significantly hinder its effectiveness. Because CAR T-cell therapy offers a potential cure, it is expected that the uptake rate will be substantially increased once the therapy is regularly funded by a health care system. Wait times may be prolonged if system resource availability does not match the demand. Strategies must be developed to minimize the impact of delays and reduce complications during waiting.

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