OAB-023: Efficacy and safety of ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy, in patients with progressive multiple myeloma after 1–3 prior lines of therapy: Initial results from CARTITUDE-2

2021 ◽  
Vol 21 ◽  
pp. S15
Author(s):  
Adam Cohen ◽  
Mounzer Agha ◽  
Deepu Madduri ◽  
Yael Cohen ◽  
Michel Delforge ◽  
...  
2018 ◽  
Vol 36 (15_suppl) ◽  
pp. TPS3103-TPS3103 ◽  
Author(s):  
Robert F. Cornell ◽  
Frederick Lundry Locke ◽  
Michael Russell Bishop ◽  
Robert Z. Orlowski ◽  
Sarah Marie Larson ◽  
...  

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 1754-1754
Author(s):  
Yunju Ma ◽  
Changju Qu ◽  
Haiping Dai ◽  
Sining Liu ◽  
Qingya Cui ◽  
...  

Abstract Background: CD19/CD22 bispecific targeted chimeric antigen receptor T cell (CAR-T) therapy has achieved impressive progress in patients with relapsed/refractory B cell acute lymphoblastic leukemia (R/R B-ALL), with high rates of complete remission (CR). However, T cell exhaustion caused by de novo DNA methylation restricts the capacity of CAR-T. Decitabine (DAC), a DNA methyltransferase inhibitor, has been demonstrated to reverse exhaustion-associated DNA-methylation programs, promote the rejuvenation of CAR-T cells and enhance anti-leukemic effect of CAR-T cells in vitro. To date, there are limited reports about the use of DAC as a part of lymphodepletion therapy before CAR-T cell therapy. Here, we report efficacy and safety of DAC in combination with fludarabine and cyclophosphamide (FC) regimen followed by CD19/CD22 CAR-T cell therapy for patients with R/R B-ALL. Method:We conducted a phase 1/2 clinical trial to investigate the efficacy and safety of CD19/CD22 CAR-T in the treatment of R/R B-ALL (NCT03614858). Fourteen patients were treated with DAC (total dose 100mg/m 2 in 3 days) followed by FC regimen (fludarabine 30mg/m 2 × 3d and cyclophosphamide 300mg/m 2 × 3d) (DAC group), while twelve patients received FC regimen prior to CAR-T cell infusion (CON group). A total of 1 or 2 × 10 7 CAR-T cells/kg were infused at dose escalation. Results: Baseline characteristics of patients in both groups had no significant differences except previous hematopoietic stem cell transplantation (HSCT). There were more patients with relapse after HSCT in DAC group (42.9% versus 0%, P=0.017). All patients did not achieve remission before lymphodepletion. The day 28 CR rates were 100% in DAC group and 91.7% in CON group. Furthermore, minimal residual disease (MRD) negative CR rates were 71.4% and 58.3%, respectively (P = 0.683). There was no significant difference in the proportion of nontransplant patients after CAR-T treatment between two groups. Among the nontransplant patients after CAR-T infusion in DAC group, 16.7% (1/6) of patients relapsed at 4 months. However, among 4 nontransplant patients in CON group, 1 patient achieved NR after CAR-T therapy and 3 patients relapsed at 1.5, 5, and 10 months. There were significant differences in overall survival (OS) and leukemia-free survival (LFS) between two groups: 3-year OS, 88.9% (DAC) versus 33.3% (CON), P = 0.01 and 3-year LFS, 92.3% (DAC) versus 21.8% (CON), P = 0.002. Multivariable analysis showed that addition of DAC to the lymphodepletion regimen was associated with better OS (hazard ratio [HR] 0.107, [95% CI, 0.013-0.875], P = 0.037) and LFS (HR 0.081, [95% CI, 0.01-0.65], P = 0.018). Cytokine release syndrome was observed in all patients. Conclusion: In summary, DAC in combination with FC regimen followed by CD19CD22 CAR-T cells was feasible and well tolerated. Our study demonstrated DAC combined with FC was an independent prognostic factor correlated with better survival in relapsed/refractory B-ALL patients. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3010-3010
Author(s):  
Aditi Sharma ◽  
Vijendra Singh ◽  
Abhinav Deol

Abstract Background: CAR (chimeric antigen receptor) T-cell therapy is a novel form of immunotherapy that utilizes genetically altered autologous T cells to target cancer cells. Since the first FDA (Food and Drug Administration) approval in August 2017, several CAR T-cell products have been approved for the treatment of various malignancies. Due to the recent approval, large-scale epidemiologic data are lacking. This study aims to characterize the epidemiology of hospitalizations for CAR T-cell therapy, readmissions, and factors associated with all-cause-30-day readmission. Methods: We performed a retrospective cohort study using the Nationwide Readmissions Database (NRD) for 2017 & 2018 to identify hospitalizations with CAR T-cell therapy administration utilizing the ICD-10-PCS (International Classification of Diseases, Tenth Revision, Procedure Coding System) codes XW033C3 & XW043C3. These admissions were further categorized into non-Hodgkin's lymphoma, leukemia, and multiple myeloma. Descriptive analysis was performed to compare demographics, hospital characteristics, various comorbid conditions, and complications between these groups. We identified primary diagnoses at readmission and all-cause 30-day readmission rate after excluding index admissions from December and deaths during index admissions. Multivariable logistic regression was used to elucidate factors associated with all-cause-30-day readmission. The analysis was carried out to produce national estimates after applying weights, and the methodology provided by the HCUP (Healthcare Cost and Utilization Project) was utilized. Results: Out of 1,322 CAR T-cell therapy admissions in 2017-2018, 909 had a diagnosis of non-Hodgkin's lymphoma, 154 had multiple myeloma, and 128 had leukemia. The median age of those with leukemia was lowest at 26 (10-42) years, followed by multiple myeloma and non-Hodgkin's at 59 (57-61) years and 63 (61-64) years, respectively (p<0.001). The majority of CAR T-cell recipients were males (63%), admitted to teaching hospitals (97.96%), had private insurance (53.01%), and belonged to the highest income communities (34.95%). The median length of stay was longest for leukemia, followed by multiple myeloma and non-Hodgkin's (18 days vs. 16 days vs. 15 days; p<0.001). Median hospital charges were highest for non-Hodgkin's, followed by leukemia and multiple myeloma ($702,484 vs. $313,366 vs. $185,854; p<0.001). Overall mortality during index hospitalization was 2.98%. The complete baseline characters are described in table 1. A total of 316 hospitalizations (25%) were readmitted within 30 days. The median time to readmission was 9 days, the median length of stay during readmission was 5 days, and crude in-hospital mortality during readmission was 3%. Readmission incurred an additional median hospital charge of $58,568. The top five diagnoses at readmission were malignancy & therapy-related (23%), sepsis or infection (19%), neurologic events (19%), neutropenia or pancytopenia (13%), and fever or hypotension (8%) (figure1). On multivariable logistic regression for predictors of 30-day readmission, admission to public hospital (aOR {adjusted odds ratio} 2.01, p 0.027), transfer to a skilled nursing facility or intermediate care facility at discharge (aOR 2.59, p 0.001), and chronic renal disease (aOR 1.47 p 0.027) were associated with higher odds of readmission. Admission to a large metro hospital (aOR 0.63 p 0.047) and teaching hospital (aOR 0.59 p 0.012) were associated with reduced odds of readmission (figure2). Conclusion: As CAR T-cell therapy has recently been added to the cancer treatment arsenal, we describe that it is associated with strikingly high hospital charges, and a quarter of recipients are readmitted within the first 30 days. Figure 1 Figure 1. Disclosures Deol: Kite, a Gilead Company: Consultancy.


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