Incidence and Management of Effusions Before and After CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy in Large B Cell Lymphoma

Mirza, Abu-Sayeef; Kumar, Amit; Hashmi, Hamza; Garcia, Franco; Logothetis, Constantine; Darwin, Alicia; Faramand, Rawan; Reid, Kayla; Bachmeier, Christina A.; Chávez, Julio C.; Shah, Bijal; Pinilla‐Ibarz, Javier; Khimani, Farhad; Lazaryan, Aleksandr; Liu, Hien; Davila, Marco L.; Nishihori, Taiga; Locke, Frederick L.; Jain, Michael D.

doi:10.1016/j.jtct.2020.12.025

Cited by 6 publications

(6 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5%). Moreover, on multivariate analysis, pre-CAR T effusions were associated with reduced OS and higher non-relapse mortality ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

“…In the Zuma-1 clinical trial, the reported CRS was 92%, in which grade 3 or worse was 11%, and the ICANS was 67%, with grade 3 or worse being 32% ( 12 ). Patients with effusions usually had a higher rate of severe CRS and non-relapse mortality rate ( 13 ) and were not eligible for Zuma-1 trial ( 12 ). Based on our studies of CAR T cells with Piggy Bac in mesothelin and EGFR ( 10 , 11 ), we generated an anti-CD19 pbCAR T. After evaluation of CD19 CAR T in terms of antitumor activity and safety, we initiated a clinical POC study that was approved by the Board of Ethics of the Shanghai Mengchao Cancer Hospital.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Rapid response in relapsed follicular lymphoma with massive chylous ascites to anti-CD19 CAR T therapy using Piggy Bac: A case report

et al. 2022

View full text Add to dashboard Cite

CD19-directed chimeric antigen receptor (CAR) T cell therapy has been shown to achieve a considerably durable response in patients with refractory or relapsed B cell non-Hodgkin lymphomas, as seen from the results of Zuma-1, Zuma-5, and other clinical trials. Most of these CARs were generated by lentivirus or reverse adenovirus. It is rare to see CARs using non-viral vectors, such as Piggy Bac (pb), in treating lymphoma patients with active diseases. Generally, patients with a high tumor burden tend to have a higher rate of severe cytokine release syndrome (CRS) or neurological events as reported in the literature. Patients with symptomatic pleural effusions are excluded from the Zuma-1 trial because of the risk of severe CRS. We report here that a patient with relapsed follicular lymphoma with bulky disease and massive chylous ascites failed several lines of chemotherapy. After infusion of the CD19-directed pbCAR-T cells at 6 × 106 cells/kg, the patient had a rapid response and achieved a nearly complete metabolic remission on day 28. There was only grade 1 CRS, and no neurotoxicity occurred. The CAR-T cells reached a peak level on day 14 and spread into the ascites and expanded for 3 months. This might be the first case reported for pbCAR-T cells to treat relapsed follicular lymphoma directly. The long-term efficacy will be observed, and more patients be tested in the future.Clinical Trial Registrationhttps://ClinicalTrials.gov, identifier NCT05472610.

show abstract

“…5%). Moreover, on multivariate analysis, pre-CAR T effusions were associated with reduced OS and higher non-relapse mortality ( 13 ).…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rapid response in relapsed follicular lymphoma with massive chylous ascites to anti-CD19 CAR T therapy using Piggy Bac: A case report

et al. 2022

View full text Add to dashboard Cite

show abstract

“…We recommend inpatient pulmonary consultation and, sometimes, early ICU admission for patients with known rapidly reaccumulating pleural effusions, patients with moderate-to-severe obstructive or restrictive pulmonary disease or moderate-to-severe pulmonary hypertension, and patients requiring home oxygen supplementation, especially if they have high tumor burden and pleural or pulmonary involvement. 5 , 23 …”

Section: Part 1: Preinfusion Cardiac and Pulmonary Evaluationmentioning

confidence: 99%

“… 6 When evaluating patients with pleural effusions, we assess whether these effusions are preexisting and secondary to underlying malignancies or new pleural effusions that develop during CRS and are more likely secondary to an inflammatory process, capillary leakage, or CAR T-cell trafficking. 5 , 22 , 23 Pleural effusions that are present at baseline before CAR T-cell therapy frequently persist, often require therapeutic intervention, and seem to be associated with higher rates of toxicity and death. In contrast, new pleural effusions that develop after CAR T-cell therapy and during CRS usually do not require drainage and are less likely to persist.…”

Section: Part 2: Crs In the Patient With High-risk Cardiac Or Pulmona...mentioning

confidence: 99%

How I approach optimization of patients at risk of cardiac and pulmonary complication after CAR-T cell therapy

Gutiérrez

Neilan

Grover

2023

Blood

View full text Add to dashboard Cite

Chimeric antigen receptor (CAR)-T cells have transformed the care of patients with hematologic malignancies. Patients treated with CAR-T cells may experience cardiovascular and pulmonary complications which primarily occur in the setting of cytokine release syndrome. In addition, many patients considered for CAR-T cell therapy have pre-existing cardiac and pulmonary comorbidities. In patients with good functional status, these conditions should not prevent patients from being offered these life-saving therapies. In this "How I Treat" article, we use a case-based approach to discuss how we evaluate and optimize patients with cardiac and pulmonary risk factors prior to CAR-T cell therapy and how we manage cardiac and pulmonary complications that may arise with treatment.

show abstract

“…Owing to its physiological features, CRS in B-NHL exhibits unique features 27 , 46 . Therefore, the classification and grading of CRS in B-NHL must be refined to help clinicians identify and manage this AE effectively.…”

Section: Crsmentioning

confidence: 99%

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Liu

Liang

et al. 2023

Cancer Biol Med

View full text Add to dashboard Cite

Adoptive cellular immunotherapy with chimeric antigen receptor (CAR) T cells has emerged as a novel modality for treating relapsed and/or refractory B-cell non-Hodgkin lymphoma (B-NHL). With increasing approval of CAR T-cell products and advances in CAR T cell therapy, CAR T cells are expected to be used in a growing number of cases. However, CAR T-cell-associated toxicities can be severe or even fatal, thus compromising the survival benefit from this therapy. Standardizing and studying the clinical management of these toxicities are imperative. In contrast to other hematological malignancies, such as acute lymphoblastic leukemia and multiple myeloma, anti-CD19 CAR T-cell-associated toxicities in B-NHL have several distinctive features, most notably local cytokine-release syndrome (CRS). However, previously published guidelines have provided few specific recommendations for the grading and management of toxicities associated with CAR T-cell treatment for B-NHL. Consequently, we developed this consensus for the prevention, recognition, and management of these toxicities, on the basis of published literature regarding the management of anti-CD19 CAR T-cell-associated toxicities and the clinical experience of multiple Chinese institutions. This consensus refines a grading system and classification of CRS in B-NHL and corresponding measures for CRS management, and delineates comprehensive principles and exploratory recommendations for managing anti-CD19 CAR T-cell-associated toxicities in addition to CRS.

show abstract

Incidence and Management of Effusions Before and After CD19-Directed Chimeric Antigen Receptor (CAR) T Cell Therapy in Large B Cell Lymphoma

Cited by 6 publications

References 17 publications

Rapid response in relapsed follicular lymphoma with massive chylous ascites to anti-CD19 CAR T therapy using Piggy Bac: A case report

Rapid response in relapsed follicular lymphoma with massive chylous ascites to anti-CD19 CAR T therapy using Piggy Bac: A case report

How I approach optimization of patients at risk of cardiac and pulmonary complication after CAR-T cell therapy

2022 Chinese expert consensus and guidelines on clinical management of toxicity in anti-CD19 chimeric antigen receptor T-cell therapy for B-cell non-Hodgkin lymphoma

Contact Info

Product

Resources

About