Abstract CT020: Immune signatures of cytokine release syndrome and neurologic events in a multicenter registrational trial (ZUMA-1) in subjects with refractory diffuse large B cell lymphoma treated with axicabtagene ciloleucel (KTE-C19)

Author(s):  
Frederick L. Locke ◽  
John Rossi ◽  
Xiaodong Xue ◽  
Sattva S. Neelapu ◽  
Daniel H. Ryan ◽  
...  
Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4845-4845
Author(s):  
Kai Hu ◽  
Shaomei Feng

Abstract Background:Tissue transformation to Diffuse large B-cell lymphoma(DLBCL) occurs in some patients with follicular cell lymphoma(FL), and these patients have a poor prognosis, and some patients do not respond well to chemotherapy, relapse or disease progression. In recent years, many clinical trials have found that CART cells are have a relatively good effect on relapsed and refractory DLBCL, but what about the effect on DLBCL transformed by FL? Methods:A total of 13 patients with diffuse large B-cell lymphoma transformed from follicular cell lymphoma who received CART cell therapy in our hospital from January 2020 to January 2021 were observed. All patients had stage III/IV disease (7 patients with stage III and 6 patients with stage IV). Among them, 10 were germinal centers and 3 were non-germinal centers. There were 8 males and 5 females, with a median age of 44 years (33-70 years old), who had undergone more than 2 chemotherapy cycles before admission to our hospital, and the median chemotherapy cycle was 10 cycles (7-19 years old). Among them, 3 had previously undergone other clinical drug trials, 1 had undergone CD20 CART cell immunotherapy, and 1 had undergone radiotherapy. At admission, ECOG was 0-3, and all patients had measurable lesions with a median size of 5cm (1.4cm-12.0cm). After preconditioning, CART cells were reinjected, 12 cases were reinjected with murine anti-CD19-CART, and 1 case was reinjected with humanized anti-CD19-CART. Median volume 3.07×10^6/kg (0.46×10^6/kg -5.43×10^6/kg). The cytokine release syndrome(CRS) and the therapeutic effect of 3 months/6 months after reinfusion were observed, and the endpoint was disease progression or death. Results:The main treatment related adverse reaction was cytokine release syndrome. Among them, there were 12 I CRS, 1 II CRS, and no treatment-related deaths. The short-term efficacy of 3 months after treatment: 4/13CR(30.8%), 7/13PR(53.8%), 2/13 SD/PD(15.4%) and ORR was 11/13 (84.6%). The efficacy of 6 months after treatment: 10/13CR(76.9%), 0/13PR(0%)and ORR was 10/13 (76.9%). One patient with 3-months CR developed disease at 11 months and died at 12 months, and one patient with 3- months PR developed disease at 5 months and died at 8 months. The remaining 6patients with 3- PR have now achieved CR。the median follow-up time was 10 months (6-19months). Of the 2 patients who did not respond to treatment have achieved PR after subsequent treatment. Conclusions: It can be seen from this study that CART cells have obvious efficacy and good safety in the treatment of DLBCL transformed by FL. It should be noted that 7 patients had PR status at 3 months after treatment, 6 patients had CR at 6 months after treatment, and 1 patient had disease progression. Efficacy evaluation of patients with DLBCL with potential transformation from FL after CART cell therapy should be appropriately delayed, except that 6 months may be the best time to evaluate the efficacy. At present, the observation time is short, PFS and OS have not been observed, and long-term observation with a larger sample is under way. Disclosures No relevant conflicts of interest to declare.


Blood ◽  
2018 ◽  
Vol 132 (8) ◽  
pp. 777-781 ◽  
Author(s):  
Victor A. Chow ◽  
Mazyar Shadman ◽  
Ajay K. Gopal

Abstract Chimeric antigen receptor T cells demonstrate efficacy in B-cell malignancies, leading to US Food and Drug Administration approval of axicabtagene ciloleucel (October 2017) and tisagenlecleucel (May 2018) for large B-cell lymphomas after 2 prior lines of therapy. Durable remissions are seen in 30% to 40% of study-treated patients, but toxicities of cytokine release syndrome and neurotoxicity require administration in specialized centers. This article reviews data of current diffuse large B-cell lymphoma management, focusing on axicabtagene ciloleucel, tisagenlecleucel, and lisocabtagene maraleucel.


Blood ◽  
2020 ◽  
Author(s):  
Gabriel K. Griffin ◽  
Jason L. Weirather ◽  
Margaretha Roemer ◽  
Mikel Lipschitz ◽  
Alyssa Kelley ◽  
...  

T-cell/histiocyte-rich large B cell lymphoma (TCRLBCL) is an aggressive variant of diffuse large B cell lymphoma (DLBCL) characterized by rare malignant B cells within a robust but ineffective immune cell infiltrate. The mechanistic basis of immune escape in TCRLBCL is poorly defined and not targeted therapeutically. We performed a genetic and quantitative spatial analysis of the PD-1/PD-L1 pathway in a multi-institutional cohort of TCRLBCLs and found that malignant B cells harbor PD-L1/PD-L2 copy gain or amplification in 64% of cases, which is associated with increased PD-L1 expression (p = 0.0111). By directed and unsupervised spatial analyses of multi-parametric cell phenotypic data within the tumor microenvironment, we found that TCRLBCL is characterized by tumor-immune 'neighborhoods' in which malignant B cells are surrounded by exceptionally high numbers of PD-L1-expressing TAMs and PD-1-positive T cells. Further, unbiased clustering of spatially-resolved immune signatures distinguished TCRLBCL from related subtypes of B-cell lymphoma, including classic Hodgkin lymphoma (cHL) and DLBCL-NOS. Finally, we observed clinical responses to PD-1 blockade in three of five patients with relapsed/refractory TCRLBCL who were enrolled in clinical trials for refractory hematologic malignancies, including two complete responses and one partial response. Taken together, these data implicate PD-1 signaling as an immune escape pathway in TCRLBCL, and also support the potential utility of spatially-resolved immune signatures to aid the diagnostic classification and immunotherapeutic prioritization of diverse tumor types.


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