Outcomes of patients with large B‐cell lymphomas and progressive disease following CD19‐specific CAR T‐cell therapy

Chow, Victor A.; Gopal, Ajay K.; Maloney, David G.; Turtle, Cameron J.; Smith, Stephen D.; Ujjani, Chaitra S.; Shadman, Mazyar; Cassaday, Ryan D.; Till, Brian G.; Tseng, Yolanda D.; Warren, Edus H.; Shustov, Andrei R.; Menon, Manoj; Bhark, Sandra L; Acharya, Utkarsh; Mullane, Erin; Hannan, Lindsay M.; Voutsinas, Jenna; Gooley, Ted; Lynch, Ryan C.

doi:10.1002/ajh.25505

Cited by 116 publications

(91 citation statements)

References 7 publications

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“…Only limited data exists on patients with progressive disease (PD) after anti-CD19 CAR-T therapy for LBCL. 3,4 As axi-cel currently accounts for the majority of CAR-T infusions in the United States, data regarding therapeutic options after progression are of great interest. 5,6 The US Lymphoma CAR-T Cell Consortium is a group of 17 US centers certified for treatment of patients with axi-cel.…”

Section: To the Editormentioning

confidence: 99%

Outcomes of Patients with Large B-cell Lymphoma Progressing after Axicabtagene Ciloleucel

Spiegel¹,

Dahiya

Jain

et al. 2020

Blood

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Section: To the Editormentioning

confidence: 99%

Outcomes of Patients with Large B-cell Lymphoma Progressing after Axicabtagene Ciloleucel

Spiegel¹,

Dahiya

Jain

et al. 2020

Blood

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“…In ZUMA-1, 12% of patients had no response to axi-cel and experienced a short OS [10]. Separately, data from 51 patients with lymphoma with progressive disease (PD) after CAR T cell therapy confirmed these patients had inferior outcomes relative to those with SD on initial assessment [59]. Collectively, these data underscore the poor prognosis associated with patients not responding to CAR T cell therapy.…”

Section: Primary Resistancementioning

confidence: 97%

“…For patients progressing after CAR T cell therapy, additional treatment with cytotoxic chemotherapy may provide shortterm disease control and improve survival, but this benefit is unlikely to be robust [59]. It must be recognized that patients evaluated in the pivotal trials had significant prior lines of therapy before CAR T cell therapy, and as the treatment is moved to earlier in the disease course, it is possible that nonresponding patients may have a higher degree of chemosensitivity.…”

Section: Primary Resistancementioning

confidence: 99%

Understanding and Managing Large B Cell Lymphoma Relapses after Chimeric Antigen Receptor T Cell Therapy

Byrne

Oluwole

Savani

et al. 2019

Biology of Blood and Marrow Transplantation

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Most patients with large cell lymphoma are cured with frontline chemoimmunotherapy. For individuals with refractory disease and those who relapse after conventional therapies, chimeric antigen receptor (CAR) T cells are an important treatment option and have led to remissions in otherwise refractory patients. In the pivotal trials, durable responses were achieved in approximately 40% to 50% of patients treated with axicabtagene ciloleucel, tisagenlecleucel, or lisocabtagene maraleucel, indicating that many patients will require subsequent treatment. Failure after CAR T cell therapy is caused by a variety of factors that can be divided into 3 broad categories: tumor intrinsic factors, other host factors, and inadequacies of the CAR T cells. Within this framework, this article reviews possible mechanisms of treatment failures and, based on the timing of relapse, considers potential salvage therapies and opportunities for future clinical studies.

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“…Another CAR T-cell therapy lisocabtagene-maraleucel, also CD19-directed, is currently under investigation in late-stage clinical trials but is not yet approved by the FDA [ 33 ]. However, emerging data with high rate of relapse or progressive disease post-CAR T-cell therapy, raise concern for bridging therapy for disease stabilization prior to CAR T-cell therapy administration, as well as subsequent therapies [ 63 ].…”

Section: Car T-cell Therapy In Hematological Malignanciesmentioning

confidence: 99%

Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies

Lin

Wang

Chen

et al. 2020

IJMS

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With advances in the understanding of characteristics of molecules, specific antigens on the surface of hematological malignant cells were identified and multiple therapies targeting these antigens as neoplasm treatments were developed. Among them, chimeric antigen receptor (CAR) T-cell therapy, which got United States Food and Drug Administration (FDA) approval for relapsed/refractory (r/r) diffuse large B-cell lymphoma (DLBCL) as well as for recurrent acute lymphoblastic leukemia (ALL) within the past five years, and for r/r mantle cell lymphoma (MCL) this year, represents one of the most rapidly evolving immunotherapies. Nevertheless, its applicability to other hematological malignancies, as well as its efficacy and persistence are fraught with clinical challenges. Currently, more than one thousand clinical trials in CAR T-cell therapy are ongoing and its development is changing rapidly. This review introduces the current status of CAR T-cell therapy in terms of the basic molecular aspects of CAR T-cell therapy, its application in hematological malignancies, adverse reactions during clinical use, remaining challenges, and future utilization.

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Outcomes of patients with large B‐cell lymphomas and progressive disease following CD19‐specific CAR T‐cell therapy

Cited by 116 publications

References 7 publications

Outcomes of Patients with Large B-cell Lymphoma Progressing after Axicabtagene Ciloleucel

Outcomes of Patients with Large B-cell Lymphoma Progressing after Axicabtagene Ciloleucel

Understanding and Managing Large B Cell Lymphoma Relapses after Chimeric Antigen Receptor T Cell Therapy

Gene Modified CAR-T Cellular Therapy for Hematologic Malignancies

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