Chimeric antigen receptor modified T cell therapy in B cell non‐Hodgkin lymphomas

Levin, Adam; Shah, Nirav N.

doi:10.1002/ajh.25403

Cited by 22 publications

(14 citation statements)

References 40 publications

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“…CAR-T-cell therapy directed at the CD19 antigen on B cells has changed the therapeutic landscape and prognosis for patients with R/R B-cell NHL, and an increasing number of patients will be receiving these treatments in the near future, but real-world data are still poor [14].…”

Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of Pixantrone for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma in Every-Day Clinical Practice: The Italian Cohort of the PIXA Registry

Zinzani

Bregni

Spione³

et al. 2020

Acta Haematol

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Introduction: Treatment of relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL) represents a challenge for clinicians due to the lack of therapeutic options. DLBCL is not a rare disease in Italy. Pixantrone is an aza-anthracenedione, which, when compared to anthracyclines and anthracenediones, has a significantly reduced cardiotoxicity while maintaining good anti-tumor activity. However, the evidence on the use of pixantrone in the context of daily clinical practice is scarce. Methods: We focused on the Italian patient subset of a larger European retrospective study (the PIXA Registry) to assess the efficacy and safety of pixantrone in a real-life DLBCL population. The molecular profile of the disease and its impact on drug efficacy were also assessed. Results: Fifteen heavily pretreated DLBCL patients (13 males and 2 females) underwent treatment with pixantrone for a median of 2 cycles (range 1–6). Eight patients were bcl2 positive, 7 bcl6 positive, and 4 myc positive; 4 patients were diagnosed as double-hit, and 2 as triple-hit DLBCL. The overall response rate was 26.7% with a best response rate of 46.7%. Three patients had grade IV adverse events, which caused drug discontinuation. Four patients had 5 cases of grade III toxicities (1 thrombocytopenia, 1 stomatitis, and 3 neutropenia). One mild cardiac toxicity (sinus tachycardia for which no action was required) was possibly related to the study drug. Conclusion: Our data documented drug efficacy that is satisfactory for this high-risk subset of patients with an acceptable toxicity profile. Results indicate that pixantrone could be a significant treatment option in patients with R/R aggressive DLBCL treated in everyday clinical practice.

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Section: Discussionmentioning

confidence: 99%

Effectiveness and Safety of Pixantrone for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma in Every-Day Clinical Practice: The Italian Cohort of the PIXA Registry

Zinzani

Bregni

Spione³

et al. 2020

Acta Haematol

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“…Genetically engineered T-cells that express chimeric antigen receptor (i.e., CAR T-cells) belong to adoptive T-cell approaches approved for the therapy of many malignancies including diffuse large B-cell lymphoma [140]. Results from the ZUMA-2 (NCT02601313) phase 2 study evaluating efficacy of autologous CD19 CAR T-cells (KTE-C19) in patients with R/R MCL are eagerly awaited.…”

Section: Salvage Therapy Of Relapsed/refractory MCL and Clonal Evomentioning

confidence: 99%

Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma

Klener

2019

IJMS

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Mantle cell lymphoma (MCL) is a heterogeneous malignancy with a broad spectrum of clinical behavior from indolent to highly aggressive cases. Despite the fact that MCL remains in most cases incurable by currently applied immunochemotherapy, our increasing knowledge on the biology of MCL in the last two decades has led to the design, testing, and approval of several innovative agents that dramatically changed the treatment landscape for MCL patients. Most importantly, the implementation of new drugs and novel treatment algorithms into clinical practice has successfully translated into improved outcomes of MCL patients not only in the clinical trials, but also in real life. This review focuses on recent advances in our understanding of the pathogenesis of MCL, and provides a brief survey of currently used treatment options with special focus on mode of action of selected innovative anti-lymphoma molecules. Finally, it outlines future perspectives of patient management with progressive shift from generally applied immunotherapy toward risk-stratified, patient-tailored protocols that would implement innovative agents and/or procedures with the ultimate goal to eradicate the lymphoma and cure the patient.

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“…Autologous CARs use the patients' T cells, which are engineered and expanded ex vivo and infused back into patients with lymphodepleting chemotherapy to enhance further expansion in vivo. CAR T cells recognizing the B cell-specific antigen CD19 are effective in the treatment of a variety of B cell malignancies (1,(4)(5)(6)(7)(8)(9). Axicabtagene ciloleucel is a commercially approved, engineered autologous anti-CD19 CAR T cell therapy in which the extracellular domain of the CAR has a single-chain variable fragment targeting CD19 and the intracellular domain has the signaling motifs of CD3ζ and CD28 to promote T cell activation (10).…”

Section: Introductionmentioning

confidence: 99%

Activation of CAR and non-CAR T cells within the tumor microenvironment following CAR T cell therapy

Chen¹,

Lipschitz²,

Weirather³

et al. 2020

JCI Insight

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Therapeutics, and Amgen; and other fees from Pieris Pharmaceutical, Boston Pharmaceuticals, and Zumutor. In addition, FSH has a patent for treating MICA-related disorders (20100111973) with royalties paid, a patent for tumor antigens and uses thereof (7250291), a pending patent for angiopoietin-2 biomarkers predictive of anti-immune checkpoint response (20170248603), a pending patent for compositions and methods for identification, assessment, prevention, and treatment of melanoma using PD-L1 Isoforms (20160340407), a pending patent for therapeutic peptides (20160046716), a pending patent for therapeutic peptides (20140004112), a pending patent for therapeutic peptides (20170022275), a pending patent for therapeutic peptides (20170008962), a pending patent for methods of using pembrolizumab and trebananib, a patent for vaccine compositions and methods for restoring NKG2D pathway function against cancers (10279021), and a patent for antibodies that bind to MHC class I polypeptide-related sequence A (2008036981A9). ZJR, SAS, JR, AB, WG are employees of Kite, a Gilead company.

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Chimeric antigen receptor modified T cell therapy in B cell non‐Hodgkin lymphomas

Cited by 22 publications

References 40 publications

Effectiveness and Safety of Pixantrone for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma in Every-Day Clinical Practice: The Italian Cohort of the PIXA Registry

Effectiveness and Safety of Pixantrone for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma in Every-Day Clinical Practice: The Italian Cohort of the PIXA Registry

Advances in Molecular Biology and Targeted Therapy of Mantle Cell Lymphoma

Activation of CAR and non-CAR T cells within the tumor microenvironment following CAR T cell therapy

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