Systematic Review and Meta-analysis of CD19-Specific CAR-T Cell Therapy in Relapsed/Refractory Acute Lymphoblastic Leukemia in the Pediatric and Young Adult Population: Safety and Efficacy Outcomes

Aamir, Sobia; Anwar, Muhammad Yasir; Khalid, Farhan; Khan, Sana Irfan; Ali, Muhammad Ashar; Khattak, Zoia Ehsan

doi:10.1016/j.clml.2020.12.010

Cited by 44 publications

(29 citation statements)

References 43 publications

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“…Other systematic reviews of CAR-T therapy in pediatric and general r/r ALL have been published; however, the focus of our analysis is on studies with primarily adult patient populations. 5,6 The results of our study will aid clinicians caring for adults with r/r B-ALL by providing a review of overall response and survival estimates of published CAR-T cell trials and will provide a general benchmark for investigators studying CAR-T cell therapies in adult ALL.…”

Section: Introductionmentioning

confidence: 99%

Chimeric antigen receptor T-cell therapy in adults with B-cell acute lymphoblastic leukemia

et al. 2022

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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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Section: Introductionmentioning

confidence: 99%

Chimeric antigen receptor T-cell therapy in adults with B-cell acute lymphoblastic leukemia

et al. 2022

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“…Intrinsic features of malignant B cells also significantly contribute to the development of resistance underlying a relapse in patients with B-ALL and high-grade lymphomas. Indeed, the relapse in B-ALL patients following CD19 CAR-T treatment can affect even half of them, but the cumulative incidence of relapse according to the meta-analysis of available clinical trials’ reports is estimated at 36% [ 90 ]. The most commonly reported causes of tumor resistance to CD19 CAR-T treatment and subsequent relapse concern various tumor cells aberrations, among which the loss of CD19 antigen is the most frequent [ 91 ].…”

Section: Mechanisms Of Resistance To the Cd19 Car-t Therapy In B Cell...mentioning

confidence: 99%

CAR-T Cells Shoot for New Targets: Novel Approaches to Boost Adoptive Cell Therapy for B Cell-Derived Malignancies

Marhelava

Krawczyk

Firczuk

et al. 2022

Cells

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Chimeric antigen receptor (CAR)-T cell therapy is undeniably a promising tool in combating various types of hematological malignancies. However, it is not yet optimal and a significant number of patients experience a lack of response or relapse after the treatment. Therapy improvement requires careful analysis of the occurring problems and a deeper understanding of the reasons that stand behind them. In this review, we summarize the recent knowledge about CAR-T products’ clinical performance and discuss diversified approaches taken to improve the major shortcomings of this therapy. Especially, we prioritize the challenges faced by CD19 CAR-T cell-based treatment of B cell-derived malignancies and revise the latest insights about mechanisms mediating therapy resistance. Since the loss of CD19 is one of the major obstacles to the success of CAR-T cell therapy, we present antigens that could be alternatively used for the treatment of various types of B cell-derived cancers.

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“… 277 These data compare with the 19% and 18% respective rates of grades 3 or higher found in a recent meta-analysis of 15 trials (N=448) of RR B-cell ALL patients who received C-19-specific CAR T-cell therapy. 278 Although tending to indicate that CRS and neurotoxicity may occur with greater frequency and severity in patients receiving CAR T-cell therapy as opposed to bi-specific antibody therapy, at least in terms of treatments targeting CD16, a number of factors, including type of malignancy under study, structure and target of the immunotherapeutic product involved, the grading scales used, and routes and timing of administration, as well as other variables may account for observed differences.…”

Section: Cytokine Release Syndrome (Crs) and Neurotoxicitymentioning

confidence: 99%

Immunotherapy of Multiple Myeloma: Promise and Challenges

Abramson

2021

ITT

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Whereas the treatment of MM was dependent solely on alkylating agents and corticosteroids during the prior three decades, the landscape of therapeutic measures to treat the disease began to expand enormously early in the current century. The introduction of new classes of small-molecule drugs, such as proteasome blockers (bortezomib and carfilzomib), immunomodulators (lenalidomide and pomalidomide), nuclear export inhibitors (selinexor), and histone deacetylase blockers (panobinostat), as well as the application of autologous stem cell transplantation (ASCT), resulted in a seismic shift in how the disease is treated. The picture changed dramatically once again starting with the 2015 FDA approval of two monoclonal antibodies (mAbs) – the anti-CD38 daratumumab and the anti-SLAMF7 elotuzumab. Daratumumab, in particular, has had a great impact on MM therapy and today is often included in various regimens to treat the disease, both in newly diagnosed cases and in the relapse/refractory setting. Recently, other immunotherapies have been added to the arsenal of drugs available to fight this malignancy. These include isatuximab (also anti-CD38) and, in the past year, the antibody-drug conjugate (ADC) belantamab mafodotin and the chimeric antigen receptor (CAR) T-cell product idecabtagene vicleucel (ide-cel). While the accumulated benefits of these newer agents have resulted in a doubling of the disease’s five-year survival rate to more than 5 years and improved quality of life, the disease remains incurable. Almost without exception patients experience relapse and/or become refractory to the drugs used, making the search for innovative therapies all the more essential. This review covers the current scope of anti-myeloma immunotherapeutic agents, both those in clinical use and on the horizon, including naked mAbs, ADCs, bi- and multi-targeted mAbs, and CAR T-cells. Emphasis is placed on the benefits of each along with the challenges that need to be overcome if MM is to be considered curable in the future.

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Systematic Review and Meta-analysis of CD19-Specific CAR-T Cell Therapy in Relapsed/Refractory Acute Lymphoblastic Leukemia in the Pediatric and Young Adult Population: Safety and Efficacy Outcomes

Cited by 44 publications

References 43 publications

Chimeric antigen receptor T-cell therapy in adults with B-cell acute lymphoblastic leukemia

Chimeric antigen receptor T-cell therapy in adults with B-cell acute lymphoblastic leukemia

CAR-T Cells Shoot for New Targets: Novel Approaches to Boost Adoptive Cell Therapy for B Cell-Derived Malignancies

Immunotherapy of Multiple Myeloma: Promise and Challenges

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