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1

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DataSheet_1.docx

Hong, Ruimin ; Tan Su Yin, Elaine ; Wang, Linqin ; [et al.]

Frontiers Media SA ; 2021

In: Frontiers in Oncology Vol. 11 ( 2021-8-4)

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In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-8-4)

Abstract: Chimeric antigen receptor (CAR) T-cell therapy has exhibited promising clinical outcomes in treating relapsed/refractory (R/R) B-cell hematologic malignancies. Current studies have shown a close correlation between baseline tumor burden and therapeutic response in CAR-T cell therapy. However, the roles of PET/CT metabolic parameters, such as metabolic tumor volume (MTV) and total lesion glycolysis (TLG), remain unclear in this setting. In this study, we retrospectively reviewed 41 R/R NHL patients. 18F-FDG PET/CT was used to measure the average standardized uptake value (SUV avg ), MTV, and TLG of the lymphomatous lesions. These patients were divided into two groups according to the optimal cutoff values of respective PET/CT metabolic parameters. The multivariate analysis depicted that early post-therapy SUV avg (HR: 1.418, 95% CI: 1.029, 1.955; p = 0.033) and MTV (HR: 1.001, 95% CI: 1.000, 1.002; p = 0.041) were independent risk factors associated with OS and PFS, respectively. Patients with baseline SUV avg & lt; 4.36 achieved a superior 1-year OS rate than the SUV avg ≥ 4.36 group (100.0% vs. 44.9%, p = 0.019). For the patients with lower values in early post-therapy SUV avg ( & lt;2.60) (51.1% vs. 0%, p & lt; 0.001), MTV ( & lt;0.55 cm 3 ) (53.6% vs. 0.0%, p = 0.001), and TLG ( & lt;1.54) (53.6% vs. 0.0%, p = 0.001), their 1-year PFS rates were higher than the compared groups. Moreover, patients with higher baseline tumor burdens were found to have significantly increased CRS incidence and cytokine levels. In conclusion, the PET/CT metabolic parameters are closely related to OS, PFS, and CRS in R/R NHL patients treated with CAR-T cells. This study may pave the way for building a comprehensive assessment system of tumor burden using 18F-FDG PET/CT, which can optimize therapeutic and supportive approaches in CAR-T cell therapy.

Type of Medium: Online Resource

ISSN: 2234-943X

URL: Article

DOI: 10.3389/fonc.2021.713577

DOI: 10.3389/fonc.2021.713577.s001

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2021

detail.hit.zdb_id: 2649216-7

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2

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Cytokine profiles are associated with prolonged hematologic toxicities after B-cell maturation antigen targeted chimeric antigen receptor–T-cell therapy

Wang, Linqin ; Hong, Ruimin ; Zhou, Linghui ; [et al.]

Elsevier BV ; 2023

In: Cytotherapy Vol. 25, No. 2 ( 2023-02), p. 192-201

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In: Cytotherapy, Elsevier BV, Vol. 25, No. 2 ( 2023-02), p. 192-201

Type of Medium: Online Resource

ISSN: 1465-3249

URL: Article

DOI: 10.1016/j.jcyt.2022.11.001

Language: English

Publisher: Elsevier BV

Publication Date: 2023

detail.hit.zdb_id: 2071176-1

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3

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CAR-T cell therapy-related cytokine release syndrome and therapeutic response is modulated by the gut microbiome in hematologic malignancies

Hu, Yongxian ; Li, Jingjing ; Ni, Fang ; [et al.]

Springer Science and Business Media LLC ; 2022

In: Nature Communications Vol. 13, No. 1 ( 2022-09-09)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2022-09-09)

Abstract: Immunotherapy utilizing chimeric antigen receptor T cell (CAR-T) therapy holds promise for hematologic malignancies, however, response rates and associated immune-related adverse effects widely vary among patients. Here we show, by comparing diversity and composition of the gut microbiome during different CAR-T therapeutic phases in the clinical trial ChiCTR1800017404, that the gut flora characteristically differs among patients and according to treatment stages, and might also reflect patient response to therapy in relapsed/refractory multiple myeloma (MM; n = 43), acute lympholastic leukemia (ALL; n = 23) and non-Hodgkin lymphoma (NHL; n = 12). We observe significant temporal differences in diversity and abundance of Bifidobacterium, Prevotella, Sutterella, and Collinsella between MM patients in complete remission ( n = 24) and those in partial remission ( n = 11). Furthermore, we find that patients with severe cytokine release syndrome present with higher abundance of Bifidobacterium, Leuconostoc, Stenotrophomonas, and Staphylococcus, which is reproducible in an independent cohort of 38 MM patients. This study has important implications for understanding the biological role of the microbiome in CAR-T treatment responsiveness of hematologic malignancy patients, and may guide therapeutic intervention to increase efficacy. The success rate of CAR-T cell therapy is high in blood cancers, yet individual patient characteristics might reduce therapeutic benefit. Here we show that therapeutic response in MM, ALL and NHL, and occurrence of severe cytokine release syndrome in multiple myeloma are associated with specific gut microbiome alterations.

Type of Medium: Online Resource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/s41467-022-32960-3

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2022

detail.hit.zdb_id: 2553671-0

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4

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Successful BCMA CAR-T Therapy for Multiple Myeloma With Central Nervous System Involvement Manifesting as Cauda Equina Syndrome—A Wandering Road to Remission

Wang, Yiyun ; Wang, Linqin ; Zeng, Yifan ; [et al.]

Frontiers Media SA ; 2021

In: Frontiers in Oncology Vol. 11 ( 2021-11-17)

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In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-11-17)

Abstract: Multiple myeloma (MM) with central nervous system (CNS) involvement is rare with only 1% incidence. So far, there is no standard or effective treatment for CNS MM, and the expected survival time is fewer than 6 months. Here, we report a case of MM with CNS involvement presented with cauda equina syndrome (CES) who achieved complete remission after anti-B-cell maturation antigen (BCMA) chimeric antigen receptor T (CAR-T) cell therapy (Chictr.org.cn, ChiCTR1800017404). The expansion of BCMA CAR-T cells was observed in both peripheral blood (PB) and cerebrospinal fluid (CSF). The CAR-T cells peaked at 2.4 × 10 6 /l in CSF at day 8 and 4.1 × 10 9 /l in PB at day 13. The peak concentration of interleukin (IL)-6 in CSF was detected 3 days earlier, and almost five times higher than that in PB. Next, morphological analysis confirmed the elimination of nucleated cells in CSF 1 month after CAR-T cell treatment from 300 cells/μl, and the patient achieved functional recovery with regressed lesion shown in PET-CT. The case demonstrated that BCMA CAR-T cells are effective and safe in this patient population.

Type of Medium: Online Resource

ISSN: 2234-943X

URL: Article

DOI: 10.3389/fonc.2021.755584

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2021

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5

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DataSheet_1.docx

Wang, Linqin ; Hong, Ruimin ; Zhou, Linghui ; [et al.]

Frontiers Media SA ; 2021

In: Frontiers in Oncology Vol. 11 ( 2021-6-30)

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In: Frontiers in Oncology, Frontiers Media SA, Vol. 11 ( 2021-6-30)

Abstract: Although chimeric antigen receptor T (CAR-T) cell therapy has proven to be effective in treating relapsed or refractory B-cell hematological malignancies, severe hematological toxicities remain an intractable issue. This retrospective study assessed the characteristics and risk factors of new-onset severe cytopenia following CAR-T cell infusion in 76 patients with r/r acute lymphoblastic leukemia. The rates of new-onset severe cytopenia were high, including severe neutropenia (SN) (39/56, 70%), severe anemia (SA) (35/66, 53%), and severe thrombocytopenia (ST) (31/64, 48%). Comparatively, cohorts with higher cytokine release syndrome (CRS) grades had higher incidence of severe cytopenia with prolonged duration. Multivariable analyses showed that elevated maximum (max) lg D-dimer and delayed peak time of CRS are independent risk factors for SN recovery; increased max lg IL-10 and delayed CRS recovery are risk factors for SA; high max lg ferritin is a risk factor for ST; and longer period to CRS onset or CRS recovery and higher grade of CRS are risk factors for prolonged hematological toxicities. These observations led to the conclusion that profiles of CRS, including its duration, severity and serum markers are correlated to the incidence and recovery of new-onset severe cytopenia, prompting clinical intervention for post-CAR-T severe cytopenia.

Type of Medium: Online Resource

ISSN: 2234-943X

URL: Article

DOI: 10.3389/fonc.2021.702644

DOI: 10.3389/fonc.2021.702644.s001

Language: Unknown

Publisher: Frontiers Media SA

Publication Date: 2021

detail.hit.zdb_id: 2649216-7

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6

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Factors Associated with Durable Progression-Free Survival in Relapsed or Refractory Multiple Myeloma Patients after Potent Anti-BCMA CAR-T Cell Therapy

Zhang, Mingming ; Zhou, Linghui ; Zhao, Houli ; [et al.]

Elsevier BV ; 2021

In: SSRN Electronic Journal

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In: SSRN Electronic Journal, Elsevier BV

Type of Medium: Online Resource

ISSN: 1556-5068

URL: Article

DOI: 10.2139/ssrn.3857669

Language: English

Publisher: Elsevier BV

Publication Date: 2021

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7

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Serial surveillance by circulating tumor DNA profiling after chimeric antigen receptor T therapy for the guidance of r/r diffuse large B cell lymphoma precise treatment

Zhou, Linghui ; Zhao, Houli ; Shao, Yang ; [et al.]

Ivyspring International Publisher ; 2021

In: Journal of Cancer Vol. 12, No. 18 ( 2021), p. 5423-5431

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In: Journal of Cancer, Ivyspring International Publisher, Vol. 12, No. 18 ( 2021), p. 5423-5431

Type of Medium: Online Resource

ISSN: 1837-9664

URL: Article

DOI: 10.7150/jca.60390

Language: English

Publisher: Ivyspring International Publisher

Publication Date: 2021

detail.hit.zdb_id: 2573318-7

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8

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Risk Factors Associated with Durable Progression-Free Survival in Patients with Relapsed or Refractory Multiple Myeloma Treated with Anti-BCMA CAR T-cell Therapy

Zhang, Mingming ; Zhou, Linghui ; Zhao, Houli ; [et al.]

American Association for Cancer Research (AACR) ; 2021

In: Clinical Cancer Research Vol. 27, No. 23 ( 2021-12-01), p. 6384-6392

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In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 27, No. 23 ( 2021-12-01), p. 6384-6392

Abstract: B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy results in high remission rates in patients with relapsed/refractory (R/R) multiple myeloma. However, the factors associated with prognosis following CAR T-cell therapy are unknown. Patients and Methods: Between July 1, 2018 and July 31, 2020, 61 patients with R/R multiple myeloma received anti-BCMA CAR T-cell therapy (Chictr.org number, ChiCTR1800017404). Step-wise multivariate Cox regression and competing risk analyses were conducted to identify poor prognosis–associated risk factors. Results: Sixty patients (98.4%) experienced cytokine release syndrome (CRS), including 33, 23, and 4 cases of CRS grades 1 to 2, 3, and 4, respectively. The objective response rate (ORR) was 98.3%, and the complete remission (CR) rate was 70.3%. With a median follow-up period of 21.1 months, the 1-year overall survival (OS) and progression-free survival (PFS) rates were 78.0% and 50.2%, respectively. The median PFS was 12.7 months. Cox modeling revealed that poor PFS was associated with extramedullary disease [HR = 2.59, 95% confidence interval (95% CI) = 1.29–5.21, P = 0.008], light chain multiple myeloma (HR = 2.53, 95% CI = 1.03–5.97, P = 0.035), high-risk cytogenetics (HR = 2.80, 95% CI = 1.27–6.14, P = 0.01), and prior treatment with more than 3 therapeutic lines (HR = 3.14, 95% CI = 1.34–7.34, P = 0.008). Among the 41 CR cases, competing risk analyses demonstrated higher relapse predispositions in those with extramedullary disease (HR = 4.51, 95% CI = 1.86–10.9, P = 0.001), light chain multiple myeloma (HR = 4.89, 95% CI = 1.52 – 15.7, P = 0.008), or high-risk cytogenetics (HR = 5.09, 95% CI = 1.63–15.9, P = 0.005). Conclusions: Anti-BCMA CAR T-cell therapy is safe and effective for R/R multiple myeloma. For patients with high-risk factors, improvements to extend remission and more specific individualized therapies are needed.

Type of Medium: Online Resource

ISSN: 1078-0432 , 1557-3265

URL: Article

DOI: 10.1158/1078-0432.CCR-21-2031

RVK:

XA 36791

Language: English

Publisher: American Association for Cancer Research (AACR)

Publication Date: 2021

detail.hit.zdb_id: 1225457-5

detail.hit.zdb_id: 2036787-9

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