Anti-CD 19 and Anti-CD 20 CAR-Modified T Cells for B-Cell Malignancies: A Systematic Review and Meta-Analysis

Riaz, Irbaz Bin; Zahid, Umar; Kamal, Muhammad Umar; Husnain, Muhammad; McBride, Ali; Hua, Anh; Hamadani, Auon Abbas; George, Laeth; Ali, Zeeshan; Sipra, Qurat Ul Ain Riaz; Raina, Ammad; Rahman, Bushra; Puvvada, Soham D.; Anwer, Faiz

doi:10.2217/imt-2017-0062

Cited by 23 publications

(22 citation statements)

References 51 publications

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“…The overall pooled RR (CR+PR) of CD19-CAR-T cells was 72% (95% CI: 62À77%), which is in agreement with previously published meta-analyses. In one analysis, the pooled CR rate was 55% and PR was 25% [13], whereas another analysis showed an overall response rate of 61% with CR of 42% and PR of 19% [12], and an overall pooled RR of 48% was reported in one study [10]. Thus, most analysis demonstrated that CAR-T therapy is effective in B-cell malignancies, and our analysis also elucidated associations between clinical response and clinical parameters that have not been previously examined in other meta-analysis.…”

Section: Discussionmentioning

confidence: 98%

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The efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies

et al. 2019

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Section: Discussionmentioning

confidence: 98%

“…In this analysis, the overall pooled RR of CD19-CAR-T cells was 73% and 93% in ALL patients and 36% in lymphoma patients. In 2017, a systematic review and meta-analysis including anti-CD19 and anti-CD20 CAR-modified T cells were involved in 16 studies with 195 patients [12]. The pooled analysis showed an overall RR of 61%.…”

Section: Introductionmentioning

confidence: 99%

The efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies

et al. 2019

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“…Use of the non-myeloablative transplant regimen containing fludarabine and cyclophosphamide improved overall response rates compared to patients who did not receive preconditioning, and this regimen therefore was taken forward in a majority of subsequent engineered ACT studies [13]. ACT engineered with chimeric antigen receptors (CARs) and high affinity T-cell receptors (TCRs) targeted against tumor-specific antigens have shown promise in the clinic [14][15][16].…”

Section: Introductionmentioning

confidence: 99%

Fludarabine and neurotoxicity in engineered T-cell therapy

Lowe

Mackall²,

Norry

et al. 2018

Gene Ther

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Adoptive T-cell therapy, incorporating engineered T cell receptors (TCRs) or chimeric antigen receptors (CARs), target tumor antigens with high affinity and specificity. To increase the potency of adoptively transferred T cells, patients are conditioned with lymphodepleting chemotherapy regimens prior to adoptive T-cell transfer (ACT), and data suggest that fludarabine is an important component of an effective regimen. In a recent clinical trial using CAR-T cells engineered to target the CD19 B-cell antigen to treat acute lymphoblastic leukemia, JCAR-015 (NCT02535364), two patient deaths due to cerebral edema led to trial suspension. The lymphodepleting agent fludarabine was suggested as the causative agent, in part due to its known association with neurotoxicity and its ability to induce greater potency. In a similar CAR-T study also incorporating fludarabine in the preconditioning regimen, ZUMA-1 (NCT02348216), one patient died of cerebral edema. However, subsequent deaths in the JCAR-015 study after removal of fludarabine and improved understanding behind the mechanisms of CAR-T-related encephalopathy syndrome (CRES) indicate that fludarabine is not the primary causative agent of cerebral edema and that it can be safely incorporated into the preconditioning regimen for ACT. Since entering clinical use in the late 1980s as a chemotherapy agent, fludarabine and similar analogs have been associated with lethal neurological toxicity, yet the manifestation and timing of symptoms are distinct to those observed recently in ACT. Herein, we review the history of fludarabine development as a chemotherapeutic agent, and discuss the safety of its continued use in preconditioning regimens for ACT.

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“…An example regulatory pathway includes PD-1/programmed cell death protein ligand 1 (PD-L1), which acts as a negative feedback loop to switch off adaptive immunity following the initial immune response (11). The CAR-T and PD-1 blockade techniques have achieved notable results in the therapy numerous types of cancers (12,13). However, a number of clinical trials have demonstrated that the efficacy of CAR-T and PD-1 blockade therapy remains limited (14)(15)(16).…”

Section: Introductionmentioning

confidence: 99%

Current status and future prospects of the strategy of combining CAR‑T with PD‑1 blockade for antitumor therapy (Review)

et al. 2017

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The immune system serves an important role in controlling and eradicating malignant cells. Immunotherapy for treating tumors has received much attention in recent years due to its marked effect. There are two approaches which currently lead this field: Chimeric antigen receptor‑modified T‑cell immunotherapy (CAR‑T) and programmed cell death protein-1 blockade (PD‑1 blockade). CAR‑T has emerged as a promising regimen for the treatment of a range of types of cancer, including chronic lymphoid leukemia and neuroblastoma, with studies of long term remission in certain patients. PD‑1 blockade has been reported to exert marked clinical responses in patients against a range of types of solid cancer, including advanced melanoma, non‑small‑cell lung cancer and renal cell carcinoma, in addition to hematological malignancies. While increasing the power of the immune system to fight cancer has been a long‑standing goal in oncology, a number of studies have demonstrated the synergistic antitumor effects of combination therapies under the umbrella of immunotherapy. The present review focused on a novel combination approach involving CAR‑T and PD‑1 blockade. The present reviews aimed to discuss the following four aspects of such an approach: i) Current monotherapy status; ii) rationale for the combination of CAR‑T and PD‑1 blockade; iii) current status of the combination of CAR‑T and PD‑1 blockade; and iv) conclusions and future perspectives.

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Anti-CD 19 and Anti-CD 20 CAR-Modified T Cells for B-Cell Malignancies: A Systematic Review and Meta-Analysis

Cited by 23 publications

References 51 publications

The efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies

The efficacy of anti-CD19 chimeric antigen receptor T cells for B-cell malignancies

Fludarabine and neurotoxicity in engineered T-cell therapy

Current status and future prospects of the strategy of combining CAR‑T with PD‑1 blockade for antitumor therapy (Review)

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