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

Abstract

Promising efficacy results of chimeric antigen receptor (CAR) T-cell therapy have been tempered by safety considerations. Our objective was to comprehensively summarize the efficacy and safety of CAR-T cell therapy in patients with relapsed or refractory hematologic or solid malignancies. MEDLINE, Embase, and the Cochrane Register of Controlled Trials (inception -November 21, 2017). Interventional studies investigating CAR-T cell therapy in patients with malignancies were included. Our primary outcome of interest was complete response (defined as the absence of detectable cancer). Two independent reviewers extracted relevant data, assessed risk of bias, and graded the quality of evidence using established methods. A total of 42 hematological malignancy studies and 18 solid tumor studies met were included (913 participants). Of 486 evaluable hematologic patients, 54.4% [95% CI, 42.5%-65.9%] experienced complete response in 27 CD19 CAR-T cell therapy studies. Of 65 evaluable hematologic patients, 24.4% [95% CI, 9.4%-50.3%] experienced complete response in seven non-CD19 CAR-T cell therapy studies. Cytokine release syndrome was experienced by 55.3% [95% CI, 40.3%-69.4%] of patients and neurotoxicity 37.2% [95% CI, 28.6%-46.8%] of patients with hematologic malignancies. Of 86 evaluable solid tumor patients, 4.1% [95% CI, 1.6%-10.6%] experienced complete response in eight CAR-T cell therapy studies. Limitations include heterogeneity of study populations, as well as high risk of bias of included studies. There was a strong signal for efficacy of CAR-T cell therapy in patients with CD19+ hematologic malignancies and no overall signal in solid tumor trials published to date. These results will help inform patients, physicians, and other stakeholders of the benefits and risks associated with CAR-T cell therapy. (M.M. Lalu). @manojlalu (M.M. Lalu).

Partnering with Patients to Get Better Outcomes with Chimeric Antigen Receptor T-cell Therapy: Towards Meaningful Patient Engagement in Early Phase Trials

“…Our patient partners identi ed quality of life and health utility measures as important outcomes to patients. We found that of the 60 clinical trials identi ed by our systematic review, none reported these outcome measures (12). Though we were unable to extract data for these outcomes, our nding points to the need for CAR-T cell therapy clinical trials to consult with patients during protocol development so that such outcomes can be measured and reported.…”

“…Chimeric Antigen Receptor (CAR) T-cell therapy, is a promising new class of personalized treatment for blood cancers, where some of a patient's own T-cells are removed, genetically modi ed in a laboratory to enable the them to speci cally target and kill cancer cells, then re-administered to the patient. Despite CAR-T therapy's promising initial results for CD19 positive blood cancers (12), further work remains to con rm both the safety and e cacy of speci c, novel CAR-T therapy products. Our team is thus conducting the rst Canadian-led, early phase clinical trial to assess the safety and effectiveness of a novel CAR-T treatment for resistant blood cancer (Trial Name: Canadian-Led Immunotherapy in Cancer Trial-01 (CLIC-01); clinicaltrials.gov registration #NCT03765177).…”

“…1, our team developed a novel iKT approach involving ve core component projects to evidence-inform a clinical trial protocol, where patients were involved from inception. Research methods and patient engagement have been described here; a more detailed description of the component studies can be found elsewhere (12,(16)(17)(18). In brief, the ve components included systematic reviews of the existing literature, interviews and a survey study to clarify patient and clinician perspectives on barriers and enablers to participation in the trial and trial delivery, an early economic analysis to assess factors that may in uence the cost of CAR-T cell therapy (to identify how to maximize economic feasibility), a retrospective cohort study to re ne eligibility criteria and assess trial feasibility, and production and testing of the cell product.…”

Building Canadian capacity for CAR‐T cells in relapsed/refractory acute lymphoblastic leukaemia: a retrospective cohort study

“…1 Among all haematologic malignancies, ALL has shown the highest response to anti-CD19 CAR-T cells with a complete response rate of 77%, as shown in a recently published meta-analysis. 8 Anti-CD19 CAR-T cells are genetically engineered T cells that express a surface single-chain immunoglobulin fragment targeting CD19 antigen found on malignant B cells. 9 The manufacturing and distribution of such therapy is complex, requiring sophisticated technology and rigorously regulated processes.…”

Efficacy and Safety of CD22 Chimeric Antigen Receptor (CAR) T-cell Therapy in Patients With B-cell Malignancies: A Protocol for a Systematic Review and Meta-analysis

“…We identi ed several systematic reviews focused on safety and e cacy of CD19 CAR T-cell therapies (20)(21)(22). Furthermore, Grigor et al and Yu et al conducted systematic reviews of all CAR T-cell therapies (23,5). These reviews only included studies up to late 2017 and early 2018, respectively, and both studies excluded conference abstracts.…”