Repeated loss of target surface antigen after immunotherapy in primary mediastinal large B cell lymphoma

Heng, Yu; Sotillo, Elena; Harrington, Colleen T.; Wertheim, Gerald; Paessler, Michele; Maude, Shannon L.; Rheingold, Susan R.; Grupp, Stephan A.; Thomas-Tikhonenko, Andrei; Pillai, Vinodh

doi:10.1002/ajh.24594

Cited by 80 publications

(60 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Antigen loss as a mechanism of relapse in lymphoma is less frequently reported than in leukemia; however, a recent report concerning primary mediastinal large B cell lymphoma showed that after CD19 CAR therapy and treatment with rituximab, loss of both CD19 and CD20 was seen. In that case, loss of DNA repair proteins in addition to clonal evolution of the lymphoma due to CAR immune pressure was the suggested mechanism (9). Multi-targeted immunotherapy may be necessary to overcome such tumor …”

Section: Sequential Loss Of Tumor Surface Antigens Following Chimericmentioning

confidence: 99%

Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Sequential Loss Of Tumor Surface Antigens Following Chimericmentioning

confidence: 99%

Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma

et al. 2018

View full text Add to dashboard Cite

show abstract

“…Antigen loss has also been reported in other lymphoma and leukemia patient populations following CAR-T cell therapy [81][82][83][84]. Examination of biopsies before CD19 CAR-T therapy and after relapse in B-ALL patients has revealed hemizygous deletions spanning the CD19 locus as well as frameshift mutations in some patients [85].…”

Section: Relapse and Resistance To Anti-cd19 Therapiesmentioning

confidence: 90%

CD19-targeted immunotherapies for treatment of patients with non-Hodgkin B-cell lymphomas

Watkins

Bartlett

2018

Expert Opinion on Investigational Drugs

View full text Add to dashboard Cite

Ubiquitous expression of CD19 on B cell non-Hodgkin lymphoma identified it as a potential target for immune-based therapies. Areas covered: This article reviews the current literature on anti-CD19 therapies currently in clinical trials including monoclonal antibodies (mAb), antibody targeted cytotoxic drug conjugates (ADC), bispecific antibodies, and chimeric antigen receptor (CAR) modified T cells. Expert opinion: Naked anti-CD19 mAbs have shown little clinical benefit in B cell lymphomas. Despite unusual toxicity profiles with many anti-CD19 ADCs slowing development, durable remissions in a substantial minority of patients with refractory aggressive lymphomas should encourage continued efforts in this area. Blinatumomab, an anti-CD19 bispecific T cell engager, has shown impressive responses in relapse/refractory diffuse large B cell lymphoma (DLBCL), but is plagued by neurotoxicity issues and the need for continuous infusion. CD19 targeting CAR-T cell therapies are the most promising, with the potential for curing a third of refractory DLBCL patients. There is still much work to be done to address potentially life-threatening cytokine release syndrome and neurotoxicity, an extended production time precluding patients with rapidly progressive disease, and treatment expense. However, if the promise of CAR-T cell technology is confirmed, this will likely change the approach and prognosis for relapse/refractory aggressive lymphoma.

show abstract

“…Relapses are either due to limited persistence of CAR T cells in the circulation, or to the loss of the CD19 target antigen on the malignant clone. Specifically, malignant B cells can escape CD19targeting therapies by loss of full-length CD19 [36][37][38], by an isoform switch to splice variants lacking extracellular antibody recognition domain of CD19 [39], or by undergoing a lineage switch to a CD19-negative, myeloid disease phenotype [40]. Antigen-negative relapses occur at an estimated frequency of about 20%.…”

Section: Disease Relapse After Car T Cell Therapymentioning

confidence: 99%

CAR T cell immunotherapy in hematology and beyond

Rossig

2018

Clinical Immunology

View full text Add to dashboard Cite

Repeated loss of target surface antigen after immunotherapy in primary mediastinal large B cell lymphoma

Cited by 80 publications

References 8 publications

Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma

Sequential loss of tumor surface antigens following chimeric antigen receptor T-cell therapies in diffuse large B-cell lymphoma

CD19-targeted immunotherapies for treatment of patients with non-Hodgkin B-cell lymphomas

CAR T cell immunotherapy in hematology and beyond

Contact Info

Product

Resources

About