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Frontiers of Medicine

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Front. Med.    2020, Vol. 14 Issue (6) : 786-791    https://doi.org/10.1007/s11684-020-0751-3
RESEARCH ARTICLE
Different sites of extranodal involvement may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen receptor T cell therapy
Lili Zhou, Ping Li, Shiguang Ye, Xiaochen Tang, Junbang Wang, Jie Liu(), Aibin Liang()
Department of Hematology, Tongji Hospital of Tongji University, Shanghai 200065, China
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Abstract

Factors associated with complete and durable remissions after anti-CD19 chimeric antigen receptor T (CAR-T) cell immunotherapy for relapsed or refractory non-Hodgkin lymphoma (r/r NHL) have not been well characterized. In this study, we found that the different sites of extranodal involvement may affect response, overall survival (OS), and progression-free survival (PFS) in patients with r/r NHL treated with anti-CD19 CAR-T cells. In a cohort of 32 treated patients, 12 (37.5%) and 8 (25%) patients exhibited soft tissue lymphoma and bone marrow (BM) infiltrations, respectively, and 13 (41%) patients exhibited infiltration at other sites. The factors that may affect prognosis were identified through multivariable analysis. As an independent risk factor, soft tissue infiltration was the only factor significantly correlated with adverse prognosis (P<0.05), whereas other factors did not reach statistical significance. Furthermore, the site of extranodal tumor infiltration significantly and negatively affected OS and PFS in patients with r/r NHL treated with anti-CD19 CAR-T cell therapy. PFS and OS in patients with BM involvement were not significantly different from those of patients with lymph node involvement alone. Thus, anti-CD19 CAR-T cell therapy may improve the prognosis of patients with BM infiltration.
Keywords anti-CD19 chimeric antigen receptor T cell      soft tissue      bone marrow      relapsed or refractory non-Hodgkin lymphoma     
Corresponding Author(s): Jie Liu,Aibin Liang   
Just Accepted Date: 13 May 2020   Online First Date: 12 August 2020    Issue Date: 24 December 2020
 Cite this article:   
Lili Zhou,Ping Li,Shiguang Ye, et al. Different sites of extranodal involvement may affect the survival of patients with relapsed or refractory non-Hodgkin lymphoma after chimeric antigen receptor T cell therapy[J]. Front. Med., 2020, 14(6): 786-791.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-020-0751-3
https://academic.hep.com.cn/fmd/EN/Y2020/V14/I6/786
Characteristic No. of patients, n (%)
Disease type
DLBCL 24 (75%)
Non-germinal center origin (GCB) 10 (31%)
Mantle cell lymphoma (MCL) 4 (12.5%)
Follicular lymphoma IIIb 1 (3.1%)
Other aggressive lymphomas 3 (9.4%)
Age
≥65 10 (31%)
<65 22 (69%)
Sex
Male 20 (62.5%)
Female 12 (37.5%)
LDH pre-lymphodepletion above the upper limit of normal 19 (59%)
International prognostic index (IPI)
0–1 16 (50%)
2 8 (25%)
3 4 (12.5%)
4–5 4 (12.5%)
Disease stage
I or II 8 (25%)
III or IV 24 (75%)
Extranodal disease
Bone marrow 8 (25%)
Soft tissue 12 (37.5%)
Others (gastrointestinal tract, pleura, adrenal gland, others) 13 (41%)
Previous therapy
Nine or more previous lines of therapy 20 (62.5%)
Previous autologous HSCT
Y 4 (12.5%)
N 28 (87.5%)
Tab.1  Patient characteristics
Fig.1  PFS and OS in patients with r/r NHL after anti-CD19 CAR-T cell therapy. Kaplan–Meier estimates of OS (A) and PFS (B) in patients with NHL who achieved CR and did not achieve CR. The Kaplan–Meier estimates of OS (C) and PFS (D) in patients with bone marrow, soft tissue, lymph node, and others involvement.
OS (95% CI, month) PFS (95% CI, month)
Bone marrow 13 (4.5–29.0) 8 (1.7–28.7)
Other sites 6 (3.3–19.6) 5 (2.6–19.2)
Lymph node 6 (4.6–13.0) 3 (2.3–10.9)
Soft tissue 3 (2.3–6.8) 2 (1.3–4.0)
Tab.2  OS and PFS of invasive tumor sites
Variable OS PFS
P Hazard ratio 95% CI P Hazard ratio 95% CI
LDH* 0.807 1.164 0.344–3.942 0.606 1.254 0.531–2.961
Soft tissue 0.004 13.788 2.344–81.106 0.006 5.006 1.584–15.823
Bone marrow 0.352 0.522 0.133–2.051 0.532 0.683 0.207–2.256
Lymph node 0.748 0.751 0.131–4.297 0.302 1.804 0.588–5.533
Other sites 0.303 0.501 0.135–1.865 0.327 0.613 0.230–1.631
SPD 0.507 1.227 0.671–2.243 0.278 1.299 0.810–2.083
Tab.3  Multivariable analysis of factors affecting OS and PFS in patients with r/r NHL
Fig.2  Kaplan–Meier estimates of OS (A) and PFS (B) in patients with high and low expression of CD19 in peripheral blood.
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