scholarly journals Infectious Complications Following Chimeric Antigen Receptor T-Cell Therapy for Hematologic Malignancy

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2831-2831
Author(s):  
Yingnan Li ◽  
Heng Mei ◽  
Mengyi Du ◽  
Chenggong Li ◽  
Yinqiang Zhang ◽  
...  
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Cell Therapy ◽  
Bacterial Infections ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Significant Difference ◽  
Car T ◽  
Grade 3

Abstract Background CAR T-cell therapy has shown remarkable efficacy for the treatment of hematologic malignancy. However, this novel adoptive cell therapy is associated with toxicities such as cytokine release syndrome (CRS), CAR-T related encephalopathy syndrome (CRES/ICANS) and infection. While as one of the most common toxicities after CAR T-cell therapy in the first month, infectious complications have not been systematically studied. we aim to explore the incidence, clinical and microbiological characteristics and identify high risk factors for infection in patients with ALL, NHL, and MM. The trial was registered on the Chinese Clinical Trial Registry (ChiCTR-OIC-17011180; ChiCTR1800018143). Methods 72 patients with ALL, 56 patients with NHL and 42 patients with MM from January 2016 to December 2020 are involved in the cohort and the baseline data and the clinical characteristics of infection are retrospectively analyzed within 28 days. Infections were defined as a microbiologic, histopathologic, corroborating laboratory, radiographic or clinical diagnosis, and classified as bacterial (bacteremia or site infection), viral (respiratory or other), or fungal (proven or probable). Infection severity was classified as mild, moderate, severe, life-threatening, or fatal. (Young et al.Biol Blood Marrow Transplant 2016; 22:359-70.)CRS was graded by ASTCT. We used univariate and stepwise multivariable Poisson regression to identify associations between baseline clinical characteristics and infection density, and Cox proportional hazards regression to assess high-risk factors for infection. Results Among 170 patients, a total of 119 infections occurred in 99 patients within 28 days, with a cumulative infection rate of 58.2%. The incidence of infection in ALL patients is higher than that of MM and NHL patients. Among 72 ALL patients, 46 (63.9%) patients developed infections, and among 42 MM patients, 24 patients (53.1%) developed infections. The difference in infections between these two groups of patients was statistically significant (Chi-Square test, P=0.038<0.05). There was no significant difference in infection between the ALL and NHL groups, and the MM patients and NHL groups had no significant difference in infection (Chi-square test: ALL vs NHL P=0.168; NHL vs MM P=0.497) . 78 patients had 98 bacterial infections and the cumulative incidence of bacterial infection was 45.9%. The cumulative incidence of viral infection was 8.24%, and fungal infection was 4.12%. Bacterial infections are the main types of infections in patients with different tumors, followed by viral infections, and finally fungal infections. There was no statistic significant difference in the severity of infection among different tumors, whether it was the number of patients or events (Kruskal-Wallis test, P=0.646 ,P=0.605） 75 infection events occurred in patients who were agranulocytosis, and 90% of patients with bloodstream infections had neutropenia at the time of infection. When agranulocytosis lasted for 28 days, the cumulative infection rate was 38.8%. 91 patients had both CRS and infection. The cumulative incidence of CRS and infection was 68.8% and 58.2%, respectively. Among patients with grade 3-4 CRS, 18 of 30 infections (60%) occurred after the peak of CRS. The adjusted baseline characteristic model showed that ALL patients, previous 30 days of infection history, refractory disease, ANC<0.5×10 9/L before infusion and≥4 prior antitumor treatment regimens had a higher infection density within 28 days; Grade 3 or 4 CRS was the only high-risk factor related to infection after infusion in the multivariate analysis. Conclusions Infection is one of the common complications of CAR-T cell therapy in patients with hematological malignancy. Bacterial infections occur in most patients regardless of the type of disease. ALL patients, previous 30 days of infection history，refractory disease, ANC<0.5×10 9/L before infusion and Grade 3 or 4 CRS are risk factors for infection. Keywords：chimeric antigen receptor t cell；hematological malignancy； bacterial infection Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

scholarly journals KTE-X19 anti-CD19 CAR T-cell therapy in adult relapsed/refractory acute lymphoblastic leukemia: ZUMA-3 phase 1 results

Blood ◽  
2021 ◽  
Author(s):  
Bijal D Shah ◽  
Michael R. Bishop ◽  
Olalekan O Oluwole ◽  
Aaron C Logan ◽  
Maria R. Baer ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Remission Rate ◽  
Lymphoblastic Leukemia ◽  
Phase 1 ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

ZUMA-3 is a phase 1/2 study evaluating KTE-X19, an autologous anti-CD19 chimeric antigen receptor (CAR) T-cell therapy, in adult relapsed/refractory (R/R) B-ALL. We report the phase 1 results. Following fludarabine/cyclophosphamide lymphodepletion, patients received a single infusion of KTE-X19 at 2, 1, or 0.5×106 cells/kg. The rate of dose-limiting toxicities (DLTs) within 28 days following KTE-X19 infusion was the primary endpoint. KTE-X19 was manufactured for 54 enrolled patients and administered to 45 (median age: 46 years [range, 18-77]). No DLTs occurred in the DLT-evaluable cohort. Grade ≥3 cytokine release syndrome (CRS) and neurologic events (NE) occurred in 31% and 38% of patients, respectively. To optimize the benefit-risk ratio, revised adverse event (AE) management for CRS and NE (earlier steroid use for NE and tocilizumab only for CRS) was evaluated at 1×106 cells/kg KTE-X19. In the 9 patients treated under revised AE management, 33% had grade 3 CRS and 11% had grade 3 NE, with no grade 4/5 NE. The overall complete remission rate correlated with CAR T-cell expansion and was 83% in patients treated with 1×106 cells/kg and 69% in all patients. Minimal residual disease was undetectable in all responding patients. At 22.1 months (range, 7.1-36.1) median follow-up, the median duration of remission was 17.6 months (95% CI, 5.8-17.6) in patients treated with 1×106 cells/kg and 14.5 months (95% CI, 5.8-18.1) in all patients. KTE-X19 treatment provided a high response rate and tolerable safety in adults with R/R B-ALL. Phase 2 is ongoing at 1×106 cells/kg with revised AE management.

scholarly journals Feasibility, and Efficacy of Donor-Derived cd19-Targeted Car t-Cell Therapy in Refractory/Relapsed(r/r)b-Cell Acute Lymphoblastic Leukemia (b-all) Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-6
Author(s):  
Xian Zhang ◽  
Junfang Yang ◽  
Wenqian Li ◽  
Gailing Zhang ◽  
Yunchao Su ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Backgrounds As CAR T-cell therapy is a highly personalized therapy, process of generating autologous CAR-T cells for each patient is complex and can still be problematic, particularly for heavily pre-treated patients and patients with significant leukemia burden. Here, we analyzed the feasibility and efficacy in 37 patients with refractory/relapsed (R/R) B-ALL who received CAR T-cells derived from related donors. Patients and Methods From April 2017 to May 2020, 37 R/R B-ALL patients with a median age of 19 years (3-61 years), were treated with second-generation CD19 CAR-T cells derived from donors. The data was aggregated from three clinical trials (www.clinicaltrials.gov NCT03173417; NCT02546739; and www.chictr.org.cn ChiCTR-ONC-17012829). Of the 37 patients, 28 were relapsed following allogenic hematopoietic stem cell transplant (allo-HSCT) and whose lymphocytes were collected from their transplant donors (3 HLA matched sibling and 25 haploidentical). For the remaining 9 patients without prior transplant, the lymphocytes were collected from HLA identical sibling donors (n=5) or haploidentical donors (n=4) because CAR-T cells manufacture from patient samples either failed (n=5) or blasts in peripheral blood were too high (>40%) to collect quality T-cells. The median CAR-T cell dose infused was 3×105/kg (1-30×105/kg). Results For the 28 patients who relapsed after prior allo-HSCT, 27 (96.4%) achieved CR within 30 days post CAR T-cell infusion, of which 25 (89.3%) were minimal residual disease (MRD) negative. Within one month following CAR T-cell therapy, graft-versus-host disease (GVHD) occurred in 3 patients including 1 with rash and 2 with diarrhea. A total of 19 of the 28 (67.9%) patients had cytokine release syndrome (CRS), including two patients (7.1%) with Grade 3-4 CRS. Four patients had CAR T-cell related neurotoxicity including 3 with Grade 3-4 events. With a medium follow up of 103 days (1-669days), the median overall survival (OS) was 169 days (1-668 days), and the median leukemia-free survival (LFS) was 158 days (1-438 days). After CAR T-cell therapy, 15 patients bridged into a second allo-HSCT and one of 15 patients (6.7%) relapsed following transplant, and two died from infection. There were 11 patients that did not receive a second transplantation, of which three patients (27.3%) relapsed, and four parents died (one due to relapse, one from arrhythmia and two from GVHD/infection). Two patients were lost to follow-up. The remaining nine patients had no prior transplantation. At the time of T-cell collection, the median bone marrow blasts were 90% (range: 18.5%-98.5%), and the median peripheral blood blasts were 10% (range: 0-70%). CR rate within 30 days post CAR-T was 44.4% (4/9 cases). Six patients developed CRS, including four with Grade 3 CRS. Only one patient had Grade 3 neurotoxicity. No GVHD occurred following CAR T-cell therapy. Among the nine patients, five were treated with CAR T-cells derived from HLA-identical sibling donors and three of those five patients achieved CR. One patient who achieved a CR died from disseminated intravascular coagulation (DIC) on day 16. Two patients who achieved a CR bridged into allo-HSCT, including one patient who relapsed and died. One of two patients who did not response to CAR T-cell therapy died from leukemia. Four of the nine patients were treated with CAR T-cells derived from haploidentical related donors. One of the four cases achieved a CR but died from infection on day 90. The other three patients who had no response to CAR T-cell therapy died from disease progression within 3 months (7-90 days). Altogether, seven of the nine patients died with a median time of 19 days (7-505 days). Conclusions We find that manufacturing CD19+ CAR-T cells derived from donors is feasible. For patients who relapse following allo-HSCT, the transplant donor derived CAR-T cells are safe and effective with a CR rate as high as 96.4%. If a patient did not have GVHD prior to CAR T-cell therapy, the incidence of GVHD following CAR T-cell was low. Among patients without a history of transplantation, an inability to collect autologous lymphocytes signaled that the patient's condition had already reached a very advanced stage. However, CAR T-cells derived from HLA identical siblings can still be considered in our experience, no GVHD occurred in these patients. But the efficacy of CAR T-cells from haploidentical donors was very poor. Disclosures No relevant conflicts of interest to declare.

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 Description of neurotoxicity in a series of patients treated with CAR T-cell therapy

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Catherine Belin ◽  
Perrine Devic ◽  
Xavier Ayrignac ◽  
Amélie Dos Santos ◽  
Adrien Paix ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Cognitive Disorders ◽  
Language Disorders ◽  
Motor Disorders ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Abstract Chimeric antigen receptor-modified T (CAR T) cell therapy is a highly promising treatment for haematological malignancies but is frequently associated with cytokine release syndrome and neurotoxicity. Between July 2018 and July 2019, all patients treated with CD19-targeted CAR T-cell therapy for relapsing lymphoma were followed-up longitudinally to describe neurological symptoms and their evolution over time. Four different French centres participated and 84 patients (median age 59 years, 31% females) were included. Neurotoxicity, defined as the presence of at least one neurological symptom appearing after treatment infusion, was reported in 43% of the patients. The median time to onset was 7 days after infusion with a median duration of 6 days. More than half of the patients (64%) had grade 1–2 severity and 34% had grade 3–4. CRS was observed in 80% of all patients. The most frequent neurological symptoms were cognitive signs, being severe in 36%, and were equally distributed between language disorders and cognitive disorders without language impairment. Non-pyramidal motor disorders, severe in 11%, were reported in 42% of the patients. Elevation of C-reactive protein (CRP) within 4 days after treatment was significantly correlated with the occurrence of grade 3–4 neurotoxicity. Although sometimes severe, neurotoxicity was almost always reversible. The efficacy of steroids and antiepileptic drugs remains unproven in the management of neurotoxicity. Neurotoxicity associated with CAR T-cell therapies occurs in more than 40% of patients. The clinical pattern is heterogeneous but cognitive disorders (not limited to language disorders) and, to a minor degree, non-pyramidal motor disorders, appeared as a signature of severe neurotoxicity.

scholarly journals Clinical Presentation, Management and Biomarkers of Cytokine Release Syndrome after Anti-CD19 CART-Cell Therapy for r/r ALL

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5625-5625
Author(s):  
Ping Li ◽  
Lili Zhou ◽  
Shiguang Ye ◽  
Shaoguang Li ◽  
Aibin Liang
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Clinical Presentation ◽  
Cytokine Release ◽  
Cytokine Release Syndrome ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Chimeric antigen receptor T (CAR-T) cell therapy has emerged as a novel treatment modality for B-cell malignancies. CD19-specific CAR-T cells induce high rates of initial response among patients with relapsed B-cell acute lymphoblastic leukemia (ALL). However, cytokine release syndrome (CRS) is the most common and severe toxicities of CAR T-cell therapy for ALL, and clinical experience is limited. Here, we describe the clinical presentation and management of 30 patients who presented with CRS following CAR-T cell therapy for relapsed/refractory ALL at our hospital. 12 of the 30 patients (40%) developed grade 1-2 CRS, 14 patients (46.7%) presented with grade 3-4 CRS and 2 patients (6.7%) died of grade 5 CRS. Compared with grade 1-2 CRS, grade 3-4 CRS correlated negatively with overall survival and progression-free survival (P =0.02). We found that higher ferritin levels and percentages of CD19 positive cells in blood lymphocytes cells at time of CAR-T cell infusion were associated with more severe CRS. Grade 3-4 neurotoxicity was frequently present in patients with grade ≧3 CRS. We also observed that the organ disfunctions occurred in sequence after fever onset during the period of CRS. Neurotoxicity, cardiovascular disfunction and cytopenia in some patients manifest as biphasic. Compared to use of tocilizumab for CRS ≧ grade 3, early intervention of tocilizumab for hyperpyrexia duration ≧ 6h alleviates the severity of CRS, and no patients died of severe CRS since this management approach was performed. As use of novel CAR-T cell therapy expands, the data from our clinical experience may help others anticipated the clinical course of organ function and manage CRS in CAR-T therapy. Figure Disclosures No relevant conflicts of interest to declare.

scholarly journals Fever Characteristics Associated with Toxicity and Outcome after Anti-CD19 CAR T-Cell Therapy for Aggressive Lymphoma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1612-1612 ◽  
Author(s):  
Hamza Hashmi ◽  
Alicia Darwin ◽  
Christina A Bachmeier ◽  
Julio Chavez ◽  
Bijal Shah ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Board Of Directors ◽  
Research Funding ◽  
Advisory Committees ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Background: Fever is a cardinal symptom of cytokine release syndrome (CRS) after CAR T-cell therapy with 84% of patients experiencing fever on the ZUMA-1 trial of axicabtagene ciloleucel (axi-cel). Knowledge of the patterns of fever and associated symptoms may inform the clinical management of these patients. Methods: We performed a single center retrospective study in 78 patients receiving axi-cel for large B cell lymphoma (LBCL) as of 12/31/2018. We evaluated all the patients who developed fever during lymphodepleting chemotherapy with fludarabine (Flu) and cyclophosphamide (Cy), after CAR T-cell infusion, and after administration of tocilizumab (toci); and analyzed the association of fever with toxicity rates (grade 3+ CRS and neurotoxicity) and efficacy [overall response rates (ORR) and complete response (CR) rate 6 months post CAR T-cell infusion]. Fever was defined per the Lee criteria [equal to or greater than 38 °C], CRS used the modified Lee criteria and neurotoxicity used the CARTOX grading system. Results: Fever occurred in 71/78 (91%) of patients. Rates of grade 3+ CRS and neurotoxicity were 9% (7/78) and 26% (20/78) respectively. The CR rate at 6 months was 41% (32/78). Toxicities and outcomes in patients with the described fever characteristics are shown in the Table. During lymphodepletion with Flu/Cy, fever was observed in 11% (9/78) of patients. Fever occurred within 24 hours of axi-cel infusion in 47% (37/78) and within 72 hours of axi-cel infusion in 71% (55/78) of the patients. In total, 41% (32/78) of patients were treated with anti-IL6R therapy (tocilizumab; toci) for CAR T toxicity. After the first dose of toci, fever recurred in 69% of patients (22/32), of which 34% (11/32) experienced fever recurrence within 24 hours of toci infusion. Conclusions: This is the first study to our knowledge that describes in detail the characteristics of fever after CAR T-cell therapy with axi-cel. Fever was common and occurred in 71% of the patients within 72 hours of axi-cel infusion. When toci was used, fever recurred in a majority of patients (69%) and in 1/3 of patients the fever recurred within 24 hours of toci infusion. These descriptive data may be used by clinicians to inform their expectations of fever occurring after treatment with axi-cel and/or toci. Table Disclosures Bachmeier: Kite/Gilead: Speakers Bureau. Chavez:Genentech: Speakers Bureau; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals, Inc.: Speakers Bureau. Shah:AstraZeneca: Honoraria; Novartis: Honoraria; Spectrum/Astrotech: Honoraria; Adaptive Biotechnologies: Honoraria; Pharmacyclics: Honoraria; Jazz Pharmaceuticals: Research Funding; Incyte: Research Funding; Kite/Gilead: Honoraria; Celgene/Juno: Honoraria. Pinilla Ibarz:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Sanofi: Speakers Bureau; Takeda: Consultancy, Speakers Bureau; Bayer: Speakers Bureau; TG Therapeutics: Consultancy; Teva: Consultancy; Janssen: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau. Nishihori:Novartis: Research Funding; Karyopharm: Research Funding. Lazaryan:Kadmon: Consultancy. Davila:Bellicum: Consultancy; Anixa: Consultancy; GlaxoSmithKline: Consultancy; Precision Biosciences: Consultancy; Novartis: Research Funding; Adaptive: Consultancy; Celgene: Research Funding; Atara: Research Funding. Locke:Cellular BioMedicine Group Inc.: Consultancy; Kite: Other: Scientific Advisor; Novartis: Other: Scientific Advisor. Jain:Kite/Gilead: Consultancy.

scholarly journals Prevalence and variation of CHIP in patients with aggressive lymphomas undergoing CD19-directed CAR-T-cell treatment

2022 ◽  
Author(s):  
Raphael Teipel ◽  
Frank P Kroschinsky ◽  
Michael Kramer ◽  
Theresa Kretschmann ◽  
Katharina Egger-Heidrich ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Immune Effector ◽  
Car T Cell ◽  
Markers Of Inflammation ◽  
Car T Cell Therapy ◽  
Significant Difference ◽  
Car T ◽  
Before And After

Inflammation plays an important role in CAR-T-cell therapy, especially in the pathophysiology of cytokine-release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). Clonal hematopoiesis of indetermined potential (CHIP) has also been associated with chronic inflammation. The relevance of CHIP in the context of CAR-T-cell treatment is currently widely unknown. We longitudinally evaluated the prevalence of CHIP, using a targeted deep sequencing approach in a cohort of patients with r/r B-NHL before and after CAR-T-cell treatment. The aim was to define the prevalence and variation of CHIP over time and to assess the influence on clinical inflammation syndromes (CRS/ICANS), cytopenia and outcome. Overall, 32 patients were included. CHIP was found in 11 of 32 patients (34 %) before CAR-T-cell therapy. CHIP progression was commonly detected in the later course. Patients with CHIP showed a comparable response rate to CAR-T-cell treatment but had an improved OS (not reached vs. 265 days, p=0.003). No significant difference was observed in terms of the occurrence and severity of CRS/ICANS, therapeutic usage of tocilizumab and glucocorticosteroids, paraclinical markers of inflammation (except ferritin) or dynamics of hematopoietic recovery. CHIP is commonly observed in patients undergoing CD19-directed CAR-T-cell therapy and is not associated with an inferior outcome.

scholarly journals Combination of Anti-CD19 and Anti-CD20 Chimeric Antigen Receptor T Cells for Relapsed and Refractory Diffuse Larger B Cell Lymphoma: An Open-Label, Single-Arm, Phase Ⅰ/Ⅱ Trial

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1590-1590 ◽  
Author(s):  
Wei Sang ◽  
Ming Shi ◽  
Jingjing Yang ◽  
Jiang Cao ◽  
Linyan Xu ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Therapy ◽  
T Cell Therapy ◽  
Car T Cells ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3 ◽  
Anti Cd20

Objective Chimeric antigen receptor T (CAR-T) cells therapy demonstrated remarkable efficiency in refractory and relapsed diffuse large B cell lymphoma (R/R DLBCL). Antigen-loss potentially leads to failure after single-target CAR-T cellss therapy. Aim to evaluate the efficiency and safety of double-target CAR-T cellss therapy, we performed a phase Ⅰ/Ⅱ clinical trial of combination anti-CD19 and anti-CD20 CAR-T cellss therapy for R/R DLBCL. Methods A total of 21 patients were enrolled, and patients were monitored for treatment response, toxicity and persistence. Patients received a conditioning regimen of fludarabine and cyclophosphamide followed by infusion of anti-CD19 and anti-CD20 CAR-T cellss. Results Of the 21 patients, 17 had objective response, and the ORR was 81.0% (95% CI, 58 to 95). 11 had CR, the CR rate was 52.4% (95% CI, 26 to 70). 4 of 9 patients in completed remission at 3 months remain in remission by 6 months, the CR rate was 44.4% (95% CI, 14 to 79). The median OS was 8.1 months (95% CI, 7 to 10) and the median PFS was 5.0 months (95% CI, 2 to 8). The median duration response was 6.8 months (95% CI, 4 to 10). Cytokine release syndrome (CRS) occurred in all patients. Of the 21 patients, 15 (71.4%) had grade 1-2 CRS, 6 (28.5%) had severe (≥grade 3) CRS, and no grade 5 CRS occurred. There were 5 patients with different degrees of neurotoxicity, namely CAR-T associated encephalopathy syndrome (CRES). There were 2 cases with grade 3 or above CRES, 5 of them were self-limited, and none of them died of severe CRS or CRES. There were significant differences in peak levels of IL-6 (P=0.004)、ferritin (P=0.008) and CRP (P=0.000) secretion between CRS 1-2 and CRS 3-4 patients within one month after CAR-T cell infusion. In terms of hematological toxicity, there were 11 cases of neutropenia above grade 3 (52.4%), 6 cases of anemia (28.6%) and 6 cases of thrombocytopenia (28.6%). After 12 patients with response and 1 patient without response received CAR-T cell therapy, CD19 cell subsets all disappeared after 2 weeks. The level of serum immunoglobulin in 14 patients with response decreased progressively after 1 week of treatment with CAR-T cells, and maintained at a relatively low level. Eight patients received intravenous immunoglobulin during CAR-T cell therapy. Conclusion Anti-CD19 combined with anti-CD20 CAR-T cell is effective in the treatment of R/R DLBCL patients.2. Anti-CD19 combined with anti-CD20 CAR-T cell therapy has the occurrence of CRS, CRES and hematological toxicity, and adverse reactions could be controlled. This is the first report to our knowledge of successful treatment of combination of anti-CD19 and anti-CD20 CAR-T cellss in R/R DLBCL. Our results provide strong support for further multiple-target CAR-T cells therapy, which could potentially resolve antigen-loss related failure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Axicabtagene Ciloleucel: Clinical Data for the Use of CAR T-cell Therapy in Relapsed and Refractory Large B-cell Lymphoma

2020 ◽  
pp. 106002802094423
Author(s):  
Zachery Halford ◽  
Mary Kate Anderson ◽  
Lunawati L. Bennett
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Large B Cell Lymphoma ◽  
Car T Cell Therapy ◽  
Car T ◽  
Grade 3

Objective: To evaluate the literature for axicabtagene ciloleucel (axi-cel), a first-in-class chimeric antigen receptor (CAR) T-cell therapy, in the treatment of relapsed/refractory (r/r) large B-cell lymphoma (LBCL). Data Sources: We conducted a PubMed (inception to June 22, 2020) and ClinicalTrials.gov search using the following terms: CD19, chimeric antigen receptor, and lymphoma. Study Selection and Data Extraction: All retrospective and prospective studies evaluating the use of axi-cel in LBCL were reviewed. Data Synthesis: In the pivotal ZUMA-1 trial, axi-cel exhibited unprecedented overall and complete response rates of 83% and 58%, respectively. With a median follow-up of 27.1 months, 39% of patients had ongoing responses. Furthermore, postmarketing retrospective analyses found similar response rates in a more clinically diverse LBCL patient population. Novel CAR T-cell therapy elicits unique and potentially life-threatening toxicities that include cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS). Studies reported grade ≥3 CRS in 7% to 14% of patients and grade ≥3 ICANS in 31% to 55% of patients. Relevance to Patient Care and Clinical Practice: Axi-cel was the first US Food and Drug Administration–approved genetically engineered autologous CAR T-cell agent in r/r LBCL, representing an important milestone and paradigm shift in cancer treatment. Adoptive T-cell immunotherapy is a breakthrough treatment modality requiring careful patient selection, multidisciplinary collaboration, comprehensive patient counseling, and expert training to ensure optimal treatment. Conclusions: The initial and ongoing results with axi-cel are encouraging, but long-term safety and efficacy data are lacking. Additional studies are required to identify axi-cel’s ideal place in LBCL therapy.

Quality of life (QOL) in patients undergoing CAR-T therapy versus stem cell transplant (SCT).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 6594-6594 ◽  
Author(s):  
Surbhi Sidana ◽  
Amylou C. Dueck ◽  
Michelle Burtis ◽  
Joan M. Griffin ◽  
Gita Thanarajasingam ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Therapy ◽  
Cell Transplant ◽  
Short Term ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Significant Difference ◽  
Car T

6594 Background: Given the significant short-term adverse effects of CAR-T cell therapy, it is important to evaluate its impact on QOL of patients in addition to efficacy, compared with established forms of cellular therapy like SCT. Methods: QOL was evaluated prospectively in patients undergoing CAR-T therapy, autoSCT & alloSCT for hematologic malignancies. QOL was assessed with FACT-G at baseline, 2 weeks and monthly for 6 months thereafter. Functional well-being (FWB), physical WB (PWB) emotional WB (EWB) & social WB (SWB) and change over time were compared across groups. Results: 45 patients were recruited (CAR-T: 10; Auto SCT: 22; Allo SCT: 13) with follow up for 2 weeks & 1 month available for 23 &15 patients, respectively (Table). There was no statistically significant difference in baseline total QOL scores (p=0.13), though scores were lower in the alloSCT group (85,84,68). EWB &FWB were numerically higher in the CAR-T group, followed by autoSCT group. At 2 weeks, overall QOL decreased by only 2 points in CAR-T group vs. 22 & 18 points in auto & alloSCT groups (p=0.09). Change in PWB vs. baseline was less pronounced in the CAR-T group (-1, -9, -13, p=0.03). At 1 month, overall QOL was 6 points lower than baseline in CAR-T group vs. 3 and 14 points lower in auto & alloSCT groups, respectively (p=0.34). Importantly, PWB had at least returned to baseline in the CAR-T group. Conclusions: Preliminary data show that patients undergoing CAR-T cell therapy do not experience a more significant decline in QOL compared with auto & allo SCT, and may experience fewer physical side effects in the short-term. Accrual & follow-up are ongoing. [Table: see text]

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