Sequential CD19-22 CAR T therapy induces sustained remission in children with r/r B-ALL

Pan, Jing; Zuo, Shiyu; Deng, Biping; Xu, Xiaofei; Li, Chuo; Zheng, Qinlong; Ling, Zhuojun; Wu, Song; Xu, Jinxi; Duan, Jiajia; Wang, Zelin; Yu, Xudong; Chang, Alex H.; Feng, Xiaoming; Tong, Chunrong

doi:10.1182/blood.2019003293

Cited by 114 publications

(101 citation statements)

References 17 publications

(35 reference statements)

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“…To address the possible causes of recurrence after CAR-T cell treatment and to improve long-term outcome, a cohort of studies and clinical trials have been conducted. These involved dual-signaling CAR-T cell therapies and preventive infusion of a second CAR-T cell product targeting a different antigen when a significant and sustained decline of copies of previous CAR-T cells was detected before the possibility of relapse [ 27 – 29 ].…”

Section: Discussionmentioning

confidence: 99%

Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report

Lin

et al. 2020

Biomark Res

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Background Mixed phenotype acute leukemia (MPAL) is a rare leukemia and is regarded as a high-risk entity with a poor prognosis. Induction therapy of an acute lymphoblastic leukemia type or hybrid regimen and hematopoietic stem cell transplantation has been recommended for MPAL. However, the optimal therapies for relapsed or refractory MPAL remain unclear, especially for relapse after stem cell transplantation. Donor-derived chimeric antigen receptor T (CAR-T) cell therapy may be a promising therapeutic option for patients with MPAL who express target antigens and have relapsed after stem cell transplantation. However, recurrence remains a challenge, and reinfusion of CAR-T cells is not always effective. An infusion of secondary donor-derived humanized CD19-modified CAR-T cells may be effective in inducing remission. Case presentation We report a case of MPAL with CD19 expression. The patient was treated with acute lymphoblastic leukemia-like induction and consolidation therapies but remained positive for SET-NUP214 fusion gene transcript. He subsequently underwent a haploidentical stem cell transplantation but relapsed within 6 months. He then underwent donor-derived CD19-targeted CAR-T cell therapy and achieved a sustained, complete molecular remission. Unfortunately, he developed a CD19-positive relapse after 2 years. Donor-derived humanized CD19-directed CAR-T cells induced a second complete molecular remission without severe cytokine release syndrome or acute graft-versus-host disease. Conclusion This case demonstrated the efficacy and safety of humanized donor-derived CD19-modified CAR-T cell infusion for treating the recurrence of MPAL previously exposed to murine-derived CD19-directed CAR-T cells.

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Section: Discussionmentioning

confidence: 99%

Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report

Lin

et al. 2020

Biomark Res

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“…The situation was extremely difficult in our two patients who already displayed failed allogeneic HSCT with prior GvHD. Tong and Wu et al, who led the cell therapy team in Beijing Boren Hospital, have demonstrated that CD22-CAR-T cell therapy was as effective as CD19-CAR-T cell therapy, and sequential CD19-followed by CD22-CAR-T cell therapies may prevent immune escape, resulting in prolonged response 9,10 , which was applied in Case 1 because higher expression of CD22 on leukemic cells was found. However, because of the lack of CD22 in Case 2, only CD19-CAR-T could be reasonably prepared.…”

Section: Discussionmentioning

confidence: 99%

Post-HSCT relapsed precursor B-cell ALL successfully salvaged by BiTE followed by consolidation CAR-T cell therapy: A report of two cases

Huang

Tong²,

et al. 2020

BCT

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Patients with advanced precursor B-cell acute lymphoblastic leukemia pre-B ALL , especially those who relapse after allogeneic hematopoietic stem cell transplantation HSCT , inevitably have poor outcomes. Although recently designed immunotherapies such as bispecific T-cell engager BiTE, blinatumomab antibody and chimeric antigen receptor T-cell therapy CART may provide some opportunity for disease control, it remains a challenging issue. We report two cases wherein these two treatments were combined, and we discuss the treatment outcomes, which may elicit new thoughts in this challenging field. Case Presentation Case 1 A 23-year-old woman was diagnosed with pre-B ALL with normal cytogenetics in January 2017. The initial response to induction chemotherapy of the TPOG-ALL protocol Taiwan Pediatric Oncology Group was poor. She was referred to National Taiwan University Hospital Taipei, Taiwan. After salvage therapy with mitoxantrone Novantrone plus high-dose cytosine arabinoside Ara-C in February, followed by high-dose methotrexate plus cyclophosphamide in March, leukemic cells reduced to a minimal residual level of 0.05% as measured using flow cytometry. She subsequently received a myeloablative allogeneic HSCT from her HLA-matched brother in Blood Cell Therapy-The official journal of APBMT

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“…They demonstrate the feasibility of sequentially administering CD19 CAR T cells followed by CD22 CAR T cells alongside the safety, toxicity, and efficacy of such a model. 1 Their observation suggests that sequential CAR T-cell targeting strategies may be safe and effective and provides proof-of-concept of a potential strategy that may allow for dual-antigen CAR T-cell targeting.…”

Section: The One-two Punch (Of Car T Cells)mentioning

confidence: 98%

The one-two punch (of CAR T cells)

Shah¹

2020

Blood

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Sequential CD19-22 CAR T therapy induces sustained remission in children with r/r B-ALL

Cited by 114 publications

References 17 publications

Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report

Secondary donor-derived humanized CD19-modified CAR-T cells induce remission in relapsed/refractory mixed phenotype acute leukemia after allogeneic hematopoietic stem cell transplantation: a case report

Post-HSCT relapsed precursor B-cell ALL successfully salvaged by BiTE followed by consolidation CAR-T cell therapy: A report of two cases

The one-two punch (of CAR T cells)

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