scholarly journals Building Canadian capacity for CAR‐T cells in relapsed/refractory acute lymphoblastic leukaemia: a retrospective cohort study

2020 ◽  
Vol 191 (1) ◽  
Author(s):  
Roy Khalife ◽  
Joshua Montroy ◽  
Emma J. M. Grigor ◽  
Dean A. Fergusson ◽  
Harold Atkins ◽  
...  
Keyword(s):  
T Cells ◽  
Cohort Study ◽  
Acute Lymphoblastic Leukaemia ◽  
Lymphoblastic Leukaemia ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Car T Cells ◽  
Car T

ALLCAR19: Updated Data Using AUTO1, a Novel Fast-Off Rate CD19 CAR in Relapsed/Refractory B-Cell Acute Lymphoblastic Leukaemia and Other B-Cell Malignancies

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-4
Author(s):  
Claire Roddie ◽  
Maeve A O'Reilly ◽  
Maria A V Marzolini ◽  
Leigh Wood ◽  
Juliana Dias ◽  
...  
Keyword(s):  
T Cells ◽  
Acute Lymphoblastic Leukaemia ◽  
B Cell ◽  
Lymphoblastic Leukaemia ◽  
Car T Cells ◽  
Car T ◽  
Remission Rates ◽  
Grade 3 ◽  
Experienced Grade

Introduction: Prognosis for adult B-cell Acute Lymphoblastic Leukaemia (B-ALL) is poor and there is currently no licensed CD19 Chimeric Antigen Receptor (CAR) therapeutic. We developed a novel CD19 CAR (CAT-41BBz CAR) with a fast off-rate, designed to result in more physiological T-cell activation, reduce toxicity and improve engraftment. We describe updated data from the Phase I ALLCAR19 (NCT02935257) study of AUTO1 in relapsed/refractory adult B-ALL. Methods: Manufacturing: AUTO1 utilises non-mobilised autologous leukapheresate. The first 6 products were generated using a standard dynabead/WAVE bioreactor process and subsequent products using a semi-automated closed process. Study design: Patients aged >16y underwent lymphodepletion with fludarabine (30mg/m2 x3) and cyclophosphamide (60mg/kg x1) followed by split dose CAR T-cell infusion (Day 0: if ≥20% Bone Marrow (BM) blasts, infuse 10 x 106 CAR T-cells; if <20% BM blasts, 100 x 106 CAR T-cells. At Day+9: if no grade 3-5 Cytokine Release Syndrome (CRS)/immune effector cell associated neurotoxicity syndrome (ICANS), infuse Dose 2, to a total dose of 410 x106 CAR T-cells). Study endpoints include feasibility of manufacture, grade 3-5 toxicity and remission rates at 1 and 3 months. Results: As of 13 May 2020, 24 patients have been leukapheresed, 23 products manufactured and 19 patients received at least 1 dose of AUTO1. The median age was 43y (range 18-62), 26% had prior blinatumomab, 47% had prior inotuzumab ozogamicin and 63% had prior hematopoietic stem cell transplantation (HSCT). At the time of pre-conditioning, 42% had ≥50% BM blasts. No patients experienced ≥Grade 3 CRS (Lee criteria), 3/19 (16%) experienced Grade 3 ICANS that swiftly resolved with steroids. Of 19 infused patients, 16/19 (84%) achieved Minimal Residual Disease (MRD) negative complete response (CR). Currently 6 patients have died, none related to AUTO1. 11/19 (58%) patients remain on study and continue in MRD negative remission at a median follow up of 12.2 months (range 0.6-24.4m). To date, only 2 patients underwent HSCT whilst in remission. For all treated patients, the event-free survival (EFS) at 6 months was 62% and 76% for those whose products were manufactured using the closed process. Patients exhibited robust CAR expansion (mean peak CAR T levels 716,769 copies/µg DNA). Conclusions: AUTO1 has a tolerable safety profile in adult patients with r/r B-ALL despite high disease burden. Early data shows high remission rates with 84% achieving MRD negative CR. This preliminary data supports the further development of AUTO1 as a standalone treatment in patients with r/r B-ALL. Data from additional patients and longer follow up will be presented. Furthermore, data from extension cohorts of patients with low- and high- grade B-cell Non-Hodgkin's lymphoma and chronic lymphocytic leukaemia will be presented. Figure Disclosures Roddie: Celgene: Honoraria; Gilead: Honoraria; Novartis: Honoraria. O'Reilly:Gilead: Honoraria; Novartis: Honoraria, Other: Travel support. Hartley:ADC Therapeutics: Consultancy, Current equity holder in publicly-traded company, Research Funding. Linch:Autolus: Consultancy. Pule:UCLB: Patents & Royalties; Mana Therapeutics: Other: entitled to share of revenue from patents filed by UCL; Autolus: Current Employment, Other: owns stock in and receives royalties, Patents & Royalties. Peggs:Autolus: Consultancy.

Clinical outcomes of DLBCL, follicular lymphoma (FL) and Richter transformation (RT) patients treated with ibrutinib: A real-world experience of off-label ibrutinib use.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. e19043-e19043
Author(s):  
Krista Isaac ◽  
Kaitlin Kennard ◽  
Daniel Jeffrey Landsburg ◽  
Mitchell E. Hughes ◽  
Jakub Svoboda ◽  
...  
Keyword(s):  
Cohort Study ◽  
Real World ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Stage Iv ◽  
Cell Of Origin ◽  
Kaplan Meier ◽  
Car T ◽  
Lr Test ◽  
Age Range

e19043 Background: Ibrutinib (IBR), a BTK inhibitor, is FDA approved for CLL, Waldenstrom macroglobulinemia, marginal zone lymphoma and mantle cell lymphoma. Despite limited data, IBR is being utilized as a therapy for patients (pts) with relapsed/refractory (RR) DLBCL and FL. In an effort to further characterize the efficacy of IBR in these settings, we conducted a retrospective cohort study of IBR-treated pts with DLBCL, RT or FL. Methods: A retrospective cohort study of DLBCL, RT and FL pts treated with IBR was completed. Data collected included demographics, stage, IPI, prior treatments, IBR dose/duration, reasons for discontinuation, and response. PFS and OS were estimated using the Kaplan Meier method. Results: 44 pts were identified (DLBCL: n = 24, 55%; FL: n = 12, 27%; RT: n = 8, 18%). Baseline characteristics: age (range 19 – 80), 61% male, 95% ECOG 0 - 1, 71% stage IV, 62% elevated LDH, 48% R-IPI ≥ 4. DLBCL subtypes (Hans criteria) were 46% non-GC (n = 11), 29% GC (n = 7), 25% unclassifiable (n = 6). In FL, 8% were grade 1, 59% grade 2, and 33% grade 3a. Med number of prior therapies was 5 (range 1-11). Most common reasons for IBR discontinuation were progression (35%), toxicity (20%), bridge to CAR-T (10%). PFS and OS data are shown in the table below. In DLBCL, cell of origin (Hans) did not impact outcomes (p = .97, LR test). PFS was superior in RT as compared to DLBCL (p = .03, LR test). Conclusions: In the largest single-center, real-world experience of IBR use in DLBCL, RT and FL, we validate findings reported in clinical trials. In FL, responses appear to be durable (median PFS > 10 months). Outcomes are poor in DLBCL and use of IBR as monotherapy is not recommended. Perhaps IBR is best used as a short-term bridge to more definitive therapies. Cell of origin (Hans) may not predict PFS and should not be used to select pts for IBR. Pts with RT appear to have more durable responses (vs. DLBCL) suggesting differing dependence on BTK signaling. [Table: see text]

scholarly journals Does Early ART Initiation is Better over Later ART Initiation in TB/HIV Co-infected Patients? A Retrospective Cohort Study;

2020 ◽  
Author(s):  
Desilu Mahari Desta ◽  
Tesfay Mehari Atey ◽  
Fikermaryam Girma ◽  
Kald Beshir Tuem ◽  
Abadi Kahsu Gebre ◽  
...  
Keyword(s):  
Body Mass Index ◽  
T Cells ◽  
Cohort Study ◽  
Functional Status ◽  
Treatment Outcomes ◽  
Body Mass ◽  
Retrospective Cohort Study ◽  
Cd4 T Cells ◽  
Retrospective Cohort ◽  
Art Initiation

Abstract Background: The co-infection of TB/HIV poses a significant burden in the health care system of developing countries like Ethiopia. There are conflicting results on preference of the time to initiate anti-retroviral therapy (ART) and hence assessing the survival experience and treatment outcomes associated with ART initiation is crucial to settle the controversies. The study compared the treatment outcomes in early versus later ART initiation in TB/HIV co-infected patients. Methods: A retrospective cohort study was conducted in Ayder Comprehensive Specialized Hospital and Mekelle Referral Hospital on 77 and 105 patients that started ART early and lately, respectively. An assumption for proportional hazard was met. Kaplan-Meier and life-table analyses were used to compare survival curves; and an independent samples t -test was used to compare means of the continuous variables between the two cohorts. Moreover, incidence per 100 persons-years were employed to crudely determine new morality rates and Cox regression analysis was done to find out the effects of independent variables on the outcome variables. Results: The mean survival time was 5.8 months after ART initiation. A 9.9 and 5.5 new incident mortality rates per 10,000 persons–years for the early and late ART initiation were observed, respectively. There was a statistically significant difference in mean CD4 + T cells between early (208.20 ± 11.94 cells/mm 3 ) and late (245.94 ± 11.69 cells/mm 3 ) ART initiators (t 180 = -2.213, p < 0.028). Additionally, late initiators had a better survival chance at all levels of time (Log Rank c 2 =5.56, p <0.018) than early initiators. Having normal body mass index [adjusted hazard ratio [AHR=0.263; 95% confidence interval [CI]: 0.089–0.778] and having a ‘working’ baseline functional status [AHR=0.151; 95% CI: 0.054–0.427] were found to be preventive factors from death. However, patients with < 250 CD4 + T cells/mm 3 were more likely to die earlier [AHR=12.023; 95%: 1.588–91.005] than their counterpart groups. Conclusion: This study highlights that TB/HIV co-infected patients with moderate immunosuppression who started their ART early had worse outcome than those who started their ART lately. Moreover, body mass index, baseline functional status, and CD4 count were found to be independent predictors of mortality. Keywords: Treatment outcome, early ART initiation, late ART initiation, TB/HIV co-infection

scholarly journals Does Early ART Initiation is Better than Later ART Initiation in TB/HIV Co-infected Patients? A Retrospective Cohort Study

2020 ◽  
Author(s):  
Tesfay Mehari Atey ◽  
Fikermaryam Girma ◽  
Kald Beshir Tuem ◽  
Abadi Kahsu Gebre ◽  
Hagos Gidey ◽  
...  
Keyword(s):  
Body Mass Index ◽  
T Cells ◽  
Cohort Study ◽  
Functional Status ◽  
Treatment Outcomes ◽  
Body Mass ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Cd4 Count ◽  
Art Initiation

Abstract Background: The co-infection of TB/HIV poses a significant burden in the health care system of developing countries like Ethiopia. There are conflicting results on the preference of the time to initiate antiretroviral therapy (ART) and hence assessing the survival experience and treatment outcomes associated with ART initiation is crucial to settle the controversies. The study compared the treatment outcomes in early versus later ART initiation in TB/HIV co-infected patients. Methods: A retrospective cohort study was conducted in Ayder Comprehensive Specialized Hospital and Mekelle Referral Hospital on 77 and 105 patients that started ART early and lately, respectively. An assumption for proportional hazard was met. Kaplan-Meier and life-table analyses were used to compare survival curves; and an independent samples t-test was used to compare means of the continuous variables between the two cohorts. Moreover, incidence per 100 persons-years was employed to crudely determine new morality rates, and Cox regression analysis was done to find out the effects of independent variables on the outcome variables. Results: The mean survival time was 5.8 months after ART initiation. A 9.9 and 5.5 new incident mortality rates per 10,000 persons–years for the early and late ART initiation were observed, respectively. There was a statistically significant difference in mean CD4+ T cells between early (208.20 ± 11.94 cells/mm3) and late (245.94 ± 11.69 cells/mm3) ART initiators (t180 = -2.213, p < 0.028). Additionally, late initiators had a better survival chance at all levels of time (Log Rank c2=5.56, p<0.018) than early initiators. Having normal body mass index [adjusted hazard ratio [AHR=0.263; 95% confidence interval [CI]: 0.089–0.778] and having a ‘working’ baseline functional status [AHR=0.151; 95% CI: 0.054–0.427] were found to be preventive factors from death. However, patients with < 250 CD4+ T cells/mm3 were more likely to die earlier [AHR=12.023; 95%: 1.588–91.005] than their counterpart groups.Conclusion: TB/HIV co-infected patients who had a CD4 count of below 250 cells/ul started ART regimen within two weeks of TB treatment initiation were found to have better survival outcomes than those who start ART beyond two weeks in the study settings. Moreover, female patients were more likely to die than males and, patients with the functional status of bedridden were more likely to die in contrast to working and ambulatory functional status. Moreover, body mass index, baseline functional status, and CD4 count were found to be independent predictors of mortality.

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