CD19 and CD30 CAR T-Cell Immunotherapy for High-Risk Classical Hodgkin’s Lymphoma

Abstract

BackgroundIn clinical applications of CAR T-cell therapy, life-threatening adverse events including cytokine release syndrome and neurotoxicity can lead to treatment failure. Outcomes of patients treated with anti-CD30 CAR T- cell have been disappointing in relapsing/refractory (r/r) classical Hodgkin’s Lymphoma (cHL).MethodsIn order to understand the applicable population of multiple CAR T-cell therapy, we examined the expression of CD19, CD20, and CD30 by immunohistochemistry (IHC) in 38 paraffin-embedded specimens of cHL. In the past two years, we found only one patient with cHL who is eligible for combined anti-CD19 and CD30 CAR T-cell treatment. This patient’s baseline characteristics were prone to severe adverse events. We treated this patient with low doses and multiple infusions of anti-CD19 and CD30 CAR T-cell.ResultsThe positive expression of CD19+ + CD30+ in Reed-Sternberg (RS) cells is approximately 5.2% (2/38). The patient we treated with combined anti-CD19 and CD30 CAR T-cell did not experience severe adverse events related to CAR T-cell therapy and received long term progression-free survival (PFS).ConclusionFor high risk r/r cHL patients, low doses of CAR T-cell used over different days at different times might be safe and effective. More clinical trials are warranted for CD19 and CD30 CAR T-cell combination therapy.

T-cells engineered with a novel VHH-based chimeric antigen receptor against CD19 exhibit comparable tumoricidal efficacy to their FMC63-based counterparts

“…As an example, Juno Therapeutics’ JCAR017 is currently being evaluated in an open-label Phase I/II clinical trial (NCT03331198) for the treatment of 259 individuals with R/R chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). According to a study by Xue et al., a patient with R/R classical Hodgkin’s lymphoma (cHL) was treated with low doses and repeated infusions of CD19- and CD30-redirected CAR-Ts which resulted in the prolonged progression-free survival (PFS) of the patients without any severe treatment-related toxicities ( 50 ). Xue and colleagues further highlighted the importance of combination CAR-T therapy for the treatment of cHL ( 50 ).…”

“…According to a study by Xue et al., a patient with R/R classical Hodgkin’s lymphoma (cHL) was treated with low doses and repeated infusions of CD19- and CD30-redirected CAR-Ts which resulted in the prolonged progression-free survival (PFS) of the patients without any severe treatment-related toxicities ( 50 ). Xue and colleagues further highlighted the importance of combination CAR-T therapy for the treatment of cHL ( 50 ). CD19 might also be considered a suitable target antigen in particular subtypes of MM cells, despite being absent from the dominant MM cells ( 51 ).…”

Tumor buster - where will the CAR-T cell therapy ‘missile’ go?

“…2 ). According to research (ChiCTR2000028922), a patient treated with CD19 and CD30 CAR-T cells showed a protracted PFS and no severe adverse effects (CTCAE v4.0) [ 71 ].…”

Anti-CD30 antibody–drug conjugate therapy in lymphoma: current knowledge, remaining controversies, and future perspectives

“…Efficacy was improved in a subsequent study of CD30 CAR-T cells in combination with lymphodepleting chemotherapy, in which the ORR was 62% and 1-year PFS and OS were 36% and 94%, respectively [ 64 ]. A case study has suggested that addition of a second target, such as CD19, to CAR-T cells may also result in improved responses [ 65 ]. Thus, CAR-T represents an important new therapeutic option for relapsed/refractory cHL that may improve patient outcomes in the future.…”