Risks and Benefits of Chimeric Antigen Receptor T-Cell (CAR-T) Therapy in Cancer: A Systematic Review and Meta-Analysis

IntroductionPatients with relapsed or refractory malignancies have a poor prognosis. Immunotherapy with chimeric antigen receptor T (CAR-T) cells redirects a patient’s immune cells against the tumour antigen. CAR-T cell therapy has demonstrated promise in treating patients with several haematological malignancies, including acute B-cell lymphoblastic leukaemia and B-cell lymphomas. CAR-T cell therapy for patients with other solid tumours is also being tested. Safety is an important consideration in CAR-T cell therapy given the potential for serious adverse events, including death. Previous reviews on CAR-T cell therapy have been limited in scope and methodology. Herein, we present a protocol for a systematic review to identify CAR-T cell interventional studies and examine the safety and efficacy of this therapy in patients with haematology malignancies and solid tumours.Methods and analysisWe will search MEDLINE, including In-Process and Epub Ahead of Print, EMBASE and the Cochrane Central Register of Controlled Trials from 1946 to 22 February 2017. Studies will be screened by title, abstract and full text independently and in duplicate. Studies that report administering CAR-T cells of any chimeric antigen receptor construct targeting antigens in patients with haematological malignancies and solid tumours will be eligible for inclusion. Outcomes to be extracted will include complete response rate (primary outcome), overall response rate, overall survival, relapse and adverse events. A meta-analysis will be performed to synthesise the prevalence of outcomes reported as proportions with 95% CIs. The potential for bias within included studies will be assessed using a modified Institute of Health Economics tool. Heterogeneity of effect sizes will be determined using the CochraneI2statistic.Ethics and disseminationThe review findings will be submitted for peer-reviewed journal publication and presented at relevant conferences and scientific meetings to promote knowledge transfer.PROSPERO registration numberCRD42017075331.

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Chimeric Antigen Receptor-T Cell Therapy in Adults with B-Cell Acute Lymphoblastic Leukemia: A Systematic Review

Blood Advances ◽

10.1182/bloodadvances.2020003482 ◽

2021 ◽

Author(s):

Punita Grover ◽

Olivier Veilleux ◽

Lu Tian ◽

Ryan Sun ◽

Melissa Previtera ◽

...

Keyword(s):

Systematic Review ◽

Acute Lymphoblastic Leukemia ◽

T Cell ◽

B Cell ◽

Chimeric Antigen Receptor ◽

Lymphoblastic Leukemia ◽

Antigen Receptor ◽

Car T ◽

Cell Acute Lymphoblastic Leukemia ◽

Grade 3

Chimeric antigen receptor T-cell (CAR-T) therapy has transformed treatment paradigms for relapsed/refractory (r/r) B-cell acute lymphoblastic leukemia (B-ALL) in children and younger adults. We performed a systematic review to investigate the published literature on efficacy and toxicity of CAR-T therapy in adults with r/r B-ALL. We searched MEDLINE, Embase and Cochrane Library for prospective, interventional studies and included published studies of ≥5 patients with median age at enrollment of ≥ 18 years. Risk of bias was assessed using a modified Institute of Health Economics tool. A total of 2566 records were assessed; 16 studies involving 489 patients were included in the final analysis. The mean CR rate was 81% and MRD negative remission rate was 81% at 4 weeks post CAR-T infusion. With median follow-up across studies of 24 months the cumulative 12-month probability of PFS and OS were 37% (95% CI 26-48%) and 57% (95% CI 49-65%), respectively. Relapse occurred in 40.3%; target antigen was retained in 73.2% of relapses. Across studies, any grade of CRS occurred in 82% (95% CI 61-95%) and grade 3 or higher CRS in 27% (95% CI 18-36%). Neurotoxicity of any grade occurred in 34% (95% CI 24-47%) and grade 3 or higher in 14% (95% CI 1-25%). In summary, CAR-T therapy achieves high early remission rates in adults with r/r B-ALL and represents a significant improvement over traditional salvage chemotherapy. Relapses are common and durable response remains a challenge.

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Chimeric antigen receptor T cells immunotherapy: challenges and opportunities in hematological malignancies

Immunotherapy ◽

10.2217/imt-2020-0181 ◽

2020 ◽

Vol 12 (18) ◽

pp. 1341-1357

Author(s):

Nashwa El-Khazragy ◽

Sherief Ghozy ◽

Passant Emad ◽

Mariam Mourad ◽

Diaaeldeen Razza ◽

...

Keyword(s):

T Cell ◽

Cell Therapy ◽

Chimeric Antigen Receptor ◽

Hematological Malignancies ◽

Antigen Receptor ◽

T Cell Therapy ◽

Car T Cell ◽

Car T Cell Therapy ◽

Car T ◽

Challenges And Opportunities

Taking advantage of the cellular immune system is the mainstay of the adoptive cell therapy, to induce recognition and destruction of cancer cells. The impressive demonstration of this principle is chimeric antigen receptor-modified T (CAR-T)-cell therapy, which had a major impact on treating relapsed and refractory hematological malignancies. Despite the great results of the CAR-T-cell therapy, many tumors are still able to avoid immune detection and further elimination, as well as the possible associated adverse events. Herein, we highlighted the recent advances in CAR-T-cell therapy, discussing their applications beneficial functions and side effects in hematological malignancies, illustrating the underlying challenges and opportunities. Furthermore, we provide an overview to overcome different obstacles using potential manufacture and treatment strategies.

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