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. 2022 Mar 8;6(5):1608-1618.
doi: 10.1182/bloodadvances.2020003482.

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

Punita Grover  1 , Olivier Veilleux  2 , Lu Tian  3 , Ryan Sun  4 , Melissa Previtera  5 , Emily Curran  1 , Lori Muffly  2
Affiliations

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

Punita Grover et al. Blood Adv. .

Abstract

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 the 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 with 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 complete remission (CR) rate was 81% and the measurable residual disease (MRD)-negative remission rate was 81% at 4 weeks after CAR-T infusion. With median follow-up across studies of 24 months, the cumulative 12-month probabilities of progression-free survival (PFS) and overall survival (OS) were 37% (95% CI, 26-48) and 57% (95% CI, 49-65), respectively. Relapse occurred in 40.3% of cases; target antigen was retained in 73.2% of relapses. Across studies, any grade of cytokine release syndrome (CRS) occurred in 82% of patients (95% CI, 61-95) and grade 3 or higher CRS in 27% (95% CI, 18-36). Neurotoxicity of any grade occurred in 34% of patients (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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Figures

None
Graphical abstract
Figure 1.
Figure 1.
Literature search diagram/PRISMA flow diagram.
Figure 2.
Figure 2.
CR at ∼4 weeks after CAR-T infusion: 81% (range, 72% to 89%).
Figure 3.
Figure 3.
MRD-negative remission at ∼4 weeks after CAR-T infusion: 81% (range, 70% to 88%).
Figure 4.
Figure 4.
PFS at 12 months: 37% (range, 26% to 48%).
Figure 5.
Figure 5.
OS at 12 months: 57% (range, 49% to 65%).
Figure 6.
Figure 6.
Survival curves for PFS and OS. Vertical line, 12-months; red line, the population survival curve from the meta-analysis; dotted lines, the survival curves from individual studies with different follow-up times.
Figure 7.
Figure 7.
Cumulative incidence of toxicities. n, number of studies with available data.
See this image and copyright information in PMC

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