Chimeric Antigens Receptor T Cell Therapy Improve the Prognosis of Pediatric Acute Lymphoblastic Leukemia With Persistent/Recurrent Minimal Residual Disease in First Complete Remission

Abstract

BackgroundThe presence of minimal residual disease (MRD) is an independent risk factor for poor prognosis in patients with acute lymphoblastic leukemia (ALL). Moreover, the role of chimeric antigen receptor T-cell (CAR-T) therapy in patients with MRD is currently unclear.MethodsWe conducted a prospective study to investigate the role of CAR-T therapy in patients with persistent/recurrent MRD-positive ALL in first remission.ResultsA total of 77 patients who had persistent/recurrent MRD were included. Of these patients, 43 were enrolled in the CAR-T group, 20 received chemotherapy as a bridge to allogeneic hematopoietic cell transplantation (allo-HSCT), and 14 patients received intensified chemotherapy. MRD negativity was achieved in 90.7% of the patients after CAR-T infusion. Patients who received CAR-T therapy had a higher 3-year leukemia-free survival (LFS) than patients who did not (77.8% vs. 51.1%, P = 0.033). Furthermore, patients in the CAR-T group had a higher 3-year LFS than those in the chemotherapy bridge-to-allo-HSCT group [77.8% (95% CI, 64.8–90.7%) vs. 68.7% (95% CI, 47.7–89.6%), P = 0.575] and had a significantly higher 3-year LFS than those in the intensified chemotherapy group [77.8% (95% CI, 64.8–90.7%) vs. 28.6% (95% CI, 4.9–52.3%), P = 0.001]. Among the patients who received CAR-T therapy, eight were not bridged to allo-HSCT, and six (75%) remained in remission with a median follow-up of 23.0 months after CAR-T infusion.ConclusionsOur findings show that CAR-T therapy can effectively eliminate MRD and improve survival in patients with a suboptimal MRD response.

Efficacy and safety of chimeric antigen receptor T-cell (CAR-T) therapy in hematologic malignancies: a living systematic review on comparative studies

“…One RCT was reclassified as NRSI and another one was classified as an ongoing RCT and was not still included because of its preliminary status only providing immature data for its primary outcome. 28 Therefore, two RCTs 29 , 30 and nine NRSI (two quasi-experimental studies 31 , 32 and seven cohort studies) 33 – 39 assessing the use of CAR-T in 1221 participants with B-cell lymphoma or T or B-cell acute lymphoblastic leukemia were included in the review. A detailed list with reasons for exclusion is presented in Supplemental Appendix 2 .…”

“…Regarding the three cohort studies that reported CR results, 37 – 39 no differences between CAR-T and control group were found in one study, 37 while the remaining two result in favor of the CAR-T group [CAR-T 91%; chemotherapy 71%, p = 0.036; 37 CAR-T + ASCT: 71%; ASCT: 33%, p = 0.003 38 ] ( Supplemental Appendix 4, Table S2 ).…”

“…When analyzed individually, two cohort studies 37 , 39 showed statistically significant PFS results in favor of the CAR-T [HR 0.49, 95% CI (0.25–0.98), p = 0.045; 36 CAR-T+ ASCT: 80% (95% CI; 60–98); ASCT: 44% (95% CI; 25–64), p = 0.036 38 ], while the remaining did not show differences. 34 The average certainty of evidence for this outcome could not be assessed ( Supplemental Appendix 4, Table S2 ).…”

“…Finally, five cohort studies also reported incidence of CRS, ranging from 5% to 15% in the CAR-T groups 33 , 35 , 37 – 39 None of the above studies but Wang et al 39 provided explicit information on the incidence of CRS in their comparator groups, being assumed as zero events for these arms. We did not rate the certainty of evidence for this outcome due to insufficient information for the assessment.…”

Comparable outcomes in patients with B-cell acute lymphoblastic leukemia receiving haploidentical hematopoietic stem cell transplantation: Pretransplant minimal residual disease-negative complete remission following chimeric antigen receptor T-cell therapy versus chemotherapy

“…Furthermore, previous studies illustrated the superiority of CD19 CAR-T over chemotherapy in inducing the molecular response of ALL, with an MRD − CR rate of 60%–90%. An analysis of Peking University People’s Hospital found a higher rate of MRD − CR1 in the CAR-T group than in the chemotherapy group (90.7% vs. 70.5%, p = 0.036), and patients who received allo-HSCT after CAR-T therapy had a better 3-year LFS than patients after chemotherapy (77.8% vs. 68.7%, p = 0.575) ( 31 ). In addition, a significant achievement of MRD − CR after CAR-T therapy was observed in Ph+ ALL R/R patients with poor prognosis, with an MRD − CR rate of 67.9% ( 32 ).…”